WorldWideScience

Sample records for central cholinergic integrity

  1. Central cholinergic regulation of respiration: nicotinic receptors

    Institute of Scientific and Technical Information of China (English)

    Xuesi M SHAO; Jack L FELDMAN

    2009-01-01

    Nicotinic acetylcholine receptors (nAChRs) are expressed in brainstem and spinal cord regions involved in the control of breathing. These receptors mediate central cholinergic regulation of respiration and effects of the exogenous ligand nicotine on respiratory pattern. Activation of a4* nAChRs in the preBotzinger Complex (preBotC), an essential site for normal respiratory rhythm generation in mammals, modulates excitatory glutamatergic neurotransmission and depolarizes preBotC inspiratory neurons, leading to increases in respiratory frequency. nAChRs are also present in motor nuclei innervating respiratory muscles. Activation of post- and/or extra-synaptic a4* nAChRs on hypoglossal (XII) motoneurons depolarizes these neurons, potentiating tonic and respiratory-related rhythmic activity. As perinatal nicotine exposure may contribute to the pathogenesis of sudden infant death syndrome (SIDS), we discuss the effects of perinatal nicotine exposure on development of the cholinergic and other neurotransmitter systems involved in control of breathing. Advances in understanding of the mechanisms underlying central cholinergic/nicotinic modulation of respiration provide a pharmacological basis for exploiting nAChRs as therapeutic targets for neurological disorders related to neural control of breathing such as sleep apnea and SIDS.

  2. Low-level microwave irradiation and central cholinergic systems

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.; Carino, M.A.; Horita, A.; Guy, A.W. (Univ. of Washington School of Medicine, Seattle (USA))

    1989-05-01

    Our previous research showed that 45 min of exposure to low-level, pulsed microwaves (2450-MHz, 2-microseconds pulses, 500 pps, whole-body average specific absorption rate 0.6 W/kg) decreased sodium-dependent high-affinity choline uptake in the frontal cortex and hippocampus of the rat. The effects of microwaves on central cholinergic systems were further investigated in this study. Increases in choline uptake activity in the frontal cortex, hippocampus, and hypothalamus were observed after 20 min of acute microwave exposure, and tolerance to the effect of microwaves developed in the hypothalamus, but not in the frontal cortex and hippocampus, of rats subjected to ten daily 20-min exposure sessions. Furthermore, the effects of acute microwave irradiation on central choline uptake could be blocked by pretreating the animals before exposure with the narcotic antagonist naltrexone. In another series of experiments, rats were exposed to microwaves in ten daily sessions of either 20 or 45 min, and muscarinic cholinergic receptors in different regions of the brain were studied by 3H-QNB binding assay. Decreases in concentration of receptors occurred in the frontal cortex and hippocampus of rats subjected to ten 20-min microwave exposure sessions, whereas increase in receptor concentration occurred in the hippocampus of animals exposed to ten 45-min sessions. This study also investigated the effects of microwave exposure on learning in the radial-arm maze. Rats were trained in the maze to obtain food reinforcements immediately after 20 or 45 min of microwave exposure.

  3. Central Cholinergic Neurons Are Rapidly Recruited by Reinforcement Feedback.

    Science.gov (United States)

    Hangya, Balázs; Ranade, Sachin P; Lorenc, Maja; Kepecs, Adam

    2015-08-27

    Basal forebrain cholinergic neurons constitute a major neuromodulatory system implicated in normal cognition and neurodegenerative dementias. Cholinergic projections densely innervate neocortex, releasing acetylcholine to regulate arousal, attention, and learning. However, their precise behavioral function is poorly understood because identified cholinergic neurons have never been recorded during behavior. To determine which aspects of cognition their activity might support, we recorded cholinergic neurons using optogenetic identification in mice performing an auditory detection task requiring sustained attention. We found that a non-cholinergic basal forebrain population-but not cholinergic neurons-were correlated with trial-to-trial measures of attention. Surprisingly, cholinergic neurons responded to reward and punishment with unusual speed and precision (18 ± 3 ms). Cholinergic responses were scaled by the unexpectedness of reinforcement and were highly similar across neurons and two nuclei innervating distinct cortical areas. These results reveal that the cholinergic system broadcasts a rapid and precisely timed reinforcement signal, supporting fast cortical activation and plasticity. PMID:26317475

  4. Segregated cholinergic transmission modulates dopamine neurons integrated in distinct functional circuits.

    Science.gov (United States)

    Dautan, Daniel; Souza, Albert S; Huerta-Ocampo, Icnelia; Valencia, Miguel; Assous, Maxime; Witten, Ilana B; Deisseroth, Karl; Tepper, James M; Bolam, J Paul; Gerdjikov, Todor V; Mena-Segovia, Juan

    2016-08-01

    Dopamine neurons in the ventral tegmental area (VTA) receive cholinergic innervation from brainstem structures that are associated with either movement or reward. Whereas cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. We used optogenetics and in vivo juxtacellular recording and labeling to examine the influence of brainstem cholinergic innervation of distinct neuronal subpopulations in the VTA. We found that LDT cholinergic axons selectively enhanced the bursting activity of mesolimbic dopamine neurons that were excited by aversive stimulation. In contrast, PPN cholinergic axons activated and changed the discharge properties of VTA neurons that were integrated in distinct functional circuits and were inhibited by aversive stimulation. Although both structures conveyed a reinforcing signal, they had opposite roles in locomotion. Our results demonstrate that two modes of cholinergic transmission operate in the VTA and segregate the neurons involved in different reward circuits.

  5. Cognitive impairment as a central cholinergic deficit in patients with Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Antonia Kaltsatou

    2015-06-01

    Conclusions: VCmax and ACmax are governed mainly by the action of the Parasympathetic Nervous System, through acetylcholine. The results of this study demonstrate that the CNS may be affected in MG and support the hypothesis that MG has central cholinergic effects manifested by cognitive dysfunction.

  6. Naltrexone pretreatment blocks microwave-induced changes in central cholinergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.; Carino, M.A.; Wen, Y.F.; Horita, A.; Guy, A.W. (Univ. of Washington School of Medicine, Seattle (USA))

    1991-01-01

    Repeated exposure of rats to pulsed, circularly polarized microwaves (2,450-MHz, 2-microseconds pulses at 500 pps, power density 1 mW/cm2, at an averaged, whole-body SAR of 0.6 W/kg) induced biphasic changes in the concentration of muscarinic cholinergic receptors in the central nervous system. An increase in receptor concentration occurred in the hippocampus of rats subjected to ten 45-min sessions of microwave exposure, whereas a decrease in concentration was observed in the frontal cortex and hippocampus of rats exposed to ten 20-min sessions. These findings, which confirm earlier work in the authors' laboratory, were extended to include pretreatment of rats with the narcotic antagonist naltrexone (1 mg/kg, IP) before each session of exposure. The drug treatment blocked the microwave-induced changes in cholinergic receptors in the brain. These data further support the authors' hypothesis that endogenous opioids play a role in the effects of microwaves on central cholinergic systems.

  7. A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice.

    Science.gov (United States)

    Abreu-Villaça, Yael; Correa-Santos, Monique; Dutra-Tavares, Ana C; Paes-Branco, Danielle; Nunes-Freitas, Andre; Manhães, Alex C; Filgueiras, Cláudio C; Ribeiro-Carvalho, Anderson

    2016-08-01

    The tobacco industry has gradually decreased nicotine content in cigarette smoke but the impact of this reduction on health is still controversial. Since the central cholinergic system is the primary site of action of nicotine, here, we investigated the effects of exposure of adolescent mice to tobacco smoke containing either high or low levels of nicotine on the central cholinergic system and the effects associated with cessation of exposure. From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74mg nicotine/cigarette) or 4A1 (LowNic group: 0.14mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. Cholinergic biomarkers were assessed in the cerebral cortex and midbrain by the end of exposure (PN45), at short- (PN50) and long-term (PN75) deprivation. In the cortex, nicotinic cholinergic receptor upregulation was observed with either type of cigarette. In the midbrain, upregulation was detected only in HighNic mice and remained significant in females at short-term deprivation. The high-affinity choline transporter was reduced in the cortex: of HighNic mice by the end of exposure; of both HighNic and LowNic females at short-term deprivation; of LowNic mice at long-term deprivation. These decrements were separable from effects on choline acetyltransferase and acetylcholinesterase activities, suggesting cholinergic synaptic impairment. Here, we demonstrated central cholinergic alterations in an animal model of tobacco smoke exposure during adolescence. This system was sensitive even to tobacco smoke with very low nicotine content. PMID:27287270

  8. Influence of clitoria ternatea extracts on memory and central cholinergic activity in rats.

    Science.gov (United States)

    Taranalli, A D; Cheeramkuzhy, T C

    2000-01-01

    Clitoria ternatea , commonly known as Shankpushpi, is widely used in the traditional Indian system of medicine as a brain tonic and is believed to promote memory and intelligence. We examined the effectiveness of alcoholic extracts of aerial and root parts of C. ternatea at 300 and 500 mg/kg doses orally in rats in attenuating electroshock-induced amnesia. Extracts at 300 mg/kg dose produced significant memory retention, and the root parts were found to be more effective. In order to delineate the possible mechanism through which C. ternatea elicits the anti-amnesic effects, we studied its influence on central cholinergic activity by estimating the acetylcholine content of the whole brain and acetylcholinesterase activity at different regions of the rat brain, viz., cerebral cortex, midbrain, medulla oblongata and cerebellum. Our results suggest that C. ternatea extracts increase rat brain acetylcholine content and acetyl cholinesterase a ctivity in a similar fashion to the standard cerebro protective drug Pyritinol. PMID:21214440

  9. Increased dopamine D1 receptor binding in the human mesocortical system following central cholinergic activation

    International Nuclear Information System (INIS)

    Full text: The interaction between the cholinergic and dopaminergic system has been implicated in many pathological processes including, Alzheimer's disease, schizophrenia and drug addiction. Little is known about the control of dopamine (DA) release following central cholinergic activation in humans, but experimental studies suggest that endogenously released Acetylcholine (ACh) achieved by the administration of cholinesterase inhibitors, can increase dopamine efflux in different regions of the brain. This leads to the activation of different types of post-synaptic dopaminergic receptors which belong to the family of G-protein coupled receptors (GPCRs). A common paradigm of the GPCRs desensitization is that agonist-induced receptor signaling is rapidly attenuated by receptor internalisation. Several experiments have shown that the activation of Dl receptors in acute conditions leads, within minutes, to translocation of the receptor from the surface of the neurons to the endosomal compartment in the cytoplasm and increased receptor turnover. To assess changes in Dl receptor density following an intravenous infusion of the selective cholinesterase inhibitor physostigmine salicylate (PHY), we studied eleven normal subjects (10 male and 1 female, mean age 36.1 and 61617; 9.9) using [11C]-SCH23390 and PET The binding potential (BP) for SCH23390 was significantly (p0.05). There was no statistically significant difference between baseline and physostigmine Kl ratio (p>0.05) suggesting that BP changes observed were not secondary to regional blood flow changes or to an order effect of the scans. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  10. Central muscarinic cholinergic activation alters interaction between splenic dendritic cell and CD4+CD25- T cells in experimental colitis.

    Directory of Open Access Journals (Sweden)

    Peris Munyaka

    Full Text Available BACKGROUND: The cholinergic anti-inflammatory pathway (CAP is based on vagus nerve (VN activity that regulates macrophage and dendritic cell responses in the spleen through alpha-7 nicotinic acetylcholine receptor (a7nAChR signaling. Inflammatory bowel disease (IBD patients present dysautonomia with decreased vagus nerve activity, dendritic cell and T cell over-activation. The aim of this study was to investigate whether central activation of the CAP alters the function of dendritic cells (DCs and sequential CD4+/CD25-T cell activation in the context of experimental colitis. METHODS: The dinitrobenzene sulfonic acid model of experimental colitis in C57BL/6 mice was used. Central, intracerebroventricular infusion of the M1 muscarinic acetylcholine receptor agonist McN-A-343 was used to activate CAP and vagus nerve and/or splenic nerve transection were performed. In addition, the role of α7nAChR signaling and the NF-kB pathway was studied. Serum amyloid protein (SAP-A, colonic tissue cytokines, IL-12p70 and IL-23 in isolated splenic DCs, and cytokines levels in DC-CD4+CD25-T cell co-culture were determined. RESULTS: McN-A-343 treatment reduced colonic inflammation associated with decreased pro-inflammatory Th1/Th17 colonic and splenic cytokine secretion. Splenic DCs cytokine release was modulated through α7nAChR and the NF-kB signaling pathways. Cholinergic activation resulted in decreased CD4+CD25-T cell priming. The anti-inflammatory efficacy of central cholinergic activation was abolished in mice with vagotomy or splenic neurectomy. CONCLUSIONS: Suppression of splenic immune cell activation and altered interaction between DCs and T cells are important aspects of the beneficial effect of brain activation of the CAP in experimental colitis. These findings may lead to improved therapeutic strategies in the treatment of IBD.

  11. Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

    Directory of Open Access Journals (Sweden)

    B. Cam-Etoz

    2012-03-01

    Full Text Available Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g female rats (N = 7 in each group the effects of intracerebroventricularly (icv injected adrenomedullin (ADM on blood pressure and heart rate (HR, and to determine if ADM and calcitonin gene-related peptide (CGRP receptors, peripheral V1 receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1 icv ADM (750 ng/10 µL caused an increase in both blood pressure and HR (DMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm. 2 Pretreatment with a CGRP receptor antagonist (CGRP8-37 and ADM receptor antagonist (ADM22-52 blocked the effect of central ADM on blood pressure and HR. 3 The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv. 4 The V1 receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl¹, O-me-Tyr²,Arg8]-vasopressin (V2255; 10 µg/kg, that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V1 receptors in the increasing effects of icv ADM on blood pressure and HR.

  12. Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

    Energy Technology Data Exchange (ETDEWEB)

    Cam-Etoz, B.; Isbil-Buyukcoskun, N.; Ozluk, K. [Department of Physiology, Uludag University Medical Faculty, Gorukle/Bursa (Turkey)

    2012-03-02

    Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g) female rats (N = 7 in each group) the effects of intracerebroventricularly (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral V{sub 1} receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1) icv ADM (750 ng/10 µL) caused an increase in both blood pressure and HR (ΔMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP{sub 8-37}) and ADM receptor antagonist (ADM{sub 22-52}) blocked the effect of central ADM on blood pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv) and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv) prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv). 4) The V{sub 1} receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl{sup 1}, O-me-Tyr{sup 2},Arg{sup 8}]-vasopressin (V2255; 10 µg/kg), that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V{sub 1} receptors in the increasing effects of icv ADM on blood pressure and HR.

  13. Cholinergic dysfunction in Parkinson's disease.

    Science.gov (United States)

    Müller, Martijn L T M; Bohnen, Nicolaas I

    2013-09-01

    There is increasing interest in the clinical effects of cholinergic basal forebrain and tegmental pedunculopontine complex (PPN) projection degeneration in Parkinson's disease (PD). Recent evidence supports an expanded role beyond cognitive impairment, including effects on olfaction, mood, REM sleep behavior disorder, and motor functions. Cholinergic denervation is variable in PD without dementia and may contribute to clinical symptom heterogeneity. Early in vivo imaging evidence that impaired cholinergic integrity of the PPN associates with frequent falling in PD is now confirmed by human post-mortem evidence. Brainstem cholinergic lesioning studies in primates confirm the role of the PPN in mobility impairment. Degeneration of basal forebrain cholinergic projections correlates with decreased walking speed. Cumulatively, these findings provide evidence for a new paradigm to explain dopamine-resistant features of mobility impairments in PD. Recognition of the increased clinical role of cholinergic system degeneration may motivate new research to expand indications for cholinergic therapy in PD. PMID:23943367

  14. Low-level microwave irradiations affect central cholinergic activity in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.; Horita, A.; Chou, C.K.; Guy, A.W.

    1987-01-01

    Sodium-dependent high-affinity choline uptake was measured in various regions of the brains of rats irradiated for 45 min with either pulsed or continuous-wave low-level microwaves (2,450 MHz; power density, 1 mW/cm2; average whole-body specific absorption rate, 0.6 W/kg). Pulsed microwave irradiation (2-microseconds pulses, 500 pulses/s) decreased choline uptake in the hippocampus and frontal cortex but had no significant effect on the hypothalamus, striatum, and inferior colliculus. Pretreatment with a narcotic antagonist (naloxone or naltrexone; 1 mg/kg i.p.) blocked the effect of pulsed microwaves on hippocampal choline uptake but did not significantly alter the effect on the frontal cortex. Irradiation with continuous-wave microwaves did not significantly affect choline uptake in the hippocampus, striatum, and hypothalamus but decreased the uptake in the frontal cortex. The effect on the frontal cortex was not altered by pretreatment with narcotic antagonist. These data suggest that exposure to low-level pulsed or continuous-wave microwaves leads to changes in cholinergic functions in the brain.

  15. Antibodies in Cerebrospinal Fluid of Some Alzheimer Disease Patients Recognize Cholinergic Neurons in the Rat Central Nervous System

    Science.gov (United States)

    McRae-Degueurce, Amanda; Booj, Serney; Haglid, Kenneth; Rosengren, Lars; Karlsson, Jan Erik; Karlsson, Ingvar; Wallin, Anders; Svennerholm, Lars; Gottfries, Carl-Gerhard; Dahlstrom, Annica

    1987-12-01

    The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize specific neuronal populations in the rat central nervous system. The results indicate that in a subgroup of patients this is indeed the case. The antibodies reported in this study have the following properties: (i) they recognize neuronal populations and components in the medial septum and spinal motor neurons in rats perfused with a mixture that fixes small neurotransmitter molecules; (ii) adsorption of the patient CSF with staphylococcal protein A-Sepharose and using a polyclonal antiserum against human IgG3 indicates that the immunocytochemical reaction in these brain regions is mainly due to the subclass IgG3; and (iii) the CSF immunocytochemical reaction is blocked by preincubation of the sections with a rabbit anti-acetylcholine antiserum. These results provide evidence that antibodies in the CSF of some, but not all, Alzheimer disease patients recognize acetylcholine-like epitopes in cholinergic neurons in the rat central nervous system.

  16. Libidibia ferrea Mature Seeds Promote Antinociceptive Effect by Peripheral and Central Pathway: Possible Involvement of Opioid and Cholinergic Receptors

    Directory of Open Access Journals (Sweden)

    Luis Armando Sawada

    2014-01-01

    Full Text Available Libidibia ferrea (LF is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF, partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueous extract or LPLF was administered systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF demonstrated a dose-dependent antinociceptive effect in all tests indicating both peripheral anti-inflammatory and central analgesia properties. Also, the use of atropine (5 mg/kg, naloxone (5 mg/kg in the abdominal writhing test was able to reverse the antinociceptive effect of the LPLF, indicating that at least one of LF lipids components is responsible for the dose related antinociceptive action in chemical and thermal models of nociception in mice. Together, the present results suggested that Libidibia ferrea induced antinociceptive activity is possibly related to its ability to inhibit opioid, cholinergic receptors, and cyclooxygenase-2 pathway, since its main component, linoleic acid, has been demonstrated to produce such effect in previous studies.

  17. Libidibia ferrea Mature Seeds Promote Antinociceptive Effect by Peripheral and Central Pathway: Possible Involvement of Opioid and Cholinergic Receptors

    Science.gov (United States)

    Sawada, Luis Armando; Monteiro, Vanessa Sâmia da Conçeição; Rabelo, Guilherme Rodrigues; Dias, Germana Bueno; Da Cunha, Maura; do Nascimento, José Luiz Martins; Bastos, Gilmara de Nazareth Tavares

    2014-01-01

    Libidibia ferrea (LF) is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF), partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueous extract or LPLF was administered systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF demonstrated a dose-dependent antinociceptive effect in all tests indicating both peripheral anti-inflammatory and central analgesia properties. Also, the use of atropine (5 mg/kg), naloxone (5 mg/kg) in the abdominal writhing test was able to reverse the antinociceptive effect of the LPLF, indicating that at least one of LF lipids components is responsible for the dose related antinociceptive action in chemical and thermal models of nociception in mice. Together, the present results suggested that Libidibia ferrea induced antinociceptive activity is possibly related to its ability to inhibit opioid, cholinergic receptors, and cyclooxygenase-2 pathway, since its main component, linoleic acid, has been demonstrated to produce such effect in previous studies. PMID:24860820

  18. Effects of a 60 Hz magnetic field on central cholinergic systems of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.; Carino, M.A.; Horita, A.; Guy, A.W. (Univ. of Washington, Seattle (United States))

    1993-03-15

    The authors studied the effects of an acute exposure to a 60 Hz magnetic field on sodium-dependent, high-affinity choline uptake in the brain of the rat. Decreases in uptake were observed in the frontal cortex and hippocampus after the animals were exposed to a magnetic field at flux densities [>=] 0.75 mT. These effects of the magnetic field were blocked by pretreating the animals with the narcotic antagonist naltrexone, but not by the peripheral opioid antagonist, naloxone methiodide. These data indicate that the magnetic-field-induced decreases in high-affinity choline uptake in the rat brain were mediated by endogenous opioids in the central nervous systems.

  19. Cholinergic interneurons control local circuit activity and cocaine conditioning.

    Science.gov (United States)

    Witten, Ilana B; Lin, Shih-Chun; Brodsky, Matthew; Prakash, Rohit; Diester, Ilka; Anikeeva, Polina; Gradinaru, Viviana; Ramakrishnan, Charu; Deisseroth, Karl

    2010-12-17

    Cholinergic neurons are widespread, and pharmacological modulation of acetylcholine receptors affects numerous brain processes, but such modulation entails side effects due to limitations in specificity for receptor type and target cell. As a result, causal roles of cholinergic neurons in circuits have been unclear. We integrated optogenetics, freely moving mammalian behavior, in vivo electrophysiology, and slice physiology to probe the cholinergic interneurons of the nucleus accumbens by direct excitation or inhibition. Despite representing less than 1% of local neurons, these cholinergic cells have dominant control roles, exerting powerful modulation of circuit activity. Furthermore, these neurons could be activated by cocaine, and silencing this drug-induced activity during cocaine exposure (despite the fact that the manipulation of the cholinergic interneurons was not aversive by itself) blocked cocaine conditioning in freely moving mammals.

  20. Action of cholinergic poisons on the central nervous system and effectiveness of potential antidotes. Annual report 1 Jul 81-30 Jun 82

    Energy Technology Data Exchange (ETDEWEB)

    Samson, F.; Nelson, S.

    1982-11-01

    The research aim was to determine the effects of soman, related organophosphate toxins and potential antidotes on brain regional functions in rats: The (/sup 14/C)-2-deoxyglucose procedure (2-DG) was used for mapping brain regional glucose use. Quantitative autoradiography was used for muscarinic and nicotinic cholinergic receptors. The 2-DG procedure gives a quantitative measure of glucose utilization in brain regions and is in index of the 'functional activity' in brain regions and systems. Values were determined in controls, rats with soman induced seizures, seizures induced by convulsants (DFP, strychnine, picrotoxin, pentylenetetrazol, penicillin) and soman pretreated with TAB. Brain regional cholinergic receptor maps were prepared and some regional muscarinic and nicotinic receptor densities have been quantified. Soman (112 micrograms/kg i.m.) causes strong, continuous seizures and a dramatic (2-6 fold) increase in the rate of glucose use in 10 major brain regions. Most intense increases were in septum, substants nigra reticularis and outer layer of hippcampal dendata gyrus. The overt seizures of rats induced by convulsants DFP, strychnine, picrotoxin, pentylenetetrazol and penicillin (in hippocampus) were strikingly different from that of rats with soman seizures. High doses (2X LD50) of soman in rats protected with TAB caused a 50% depression of glucose use in most brain regions. The effects of repeated soman exposure on muscarinic and nicotinic receptors are under study.

  1. Striatal cholinergic interneuron regulation and circuit effects

    Directory of Open Access Journals (Sweden)

    Sean Austin Lim

    2014-10-01

    Full Text Available The striatum plays a central role in motor control and motor learning. Appropriate responses to environmental stimuli, including pursuit of reward or avoidance of aversive experience all require functional striatal circuits. These pathways integrate synaptic inputs from limbic and cortical regions including sensory, motor and motivational information to ultimately connect intention to action. Although many neurotransmitters participate in striatal circuitry, one critically important player is acetylcholine (ACh. Relative to other brain areas, the striatum contains exceptionally high levels of ACh, the enzymes that catalyze its synthesis and breakdown, as well as both nicotinic and muscarinic receptor types that mediate its postsynaptic effects. The principal source of striatal ACh is the cholinergic interneuron (ChI, which comprises only about 1-2% of all striatal cells yet sends dense arbors of projections throughout the striatum. This review summarizes recent advances in our understanding of the factors affecting the excitability of these neurons through acute effects and long term changes in their synaptic inputs. In addition, we discuss the physiological effects of ACh in the striatum, and how changes in ACh levels may contribute to disease states during striatal dysfunction.

  2. Nematode cholinergic pharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Segerberg, M.A.

    1989-01-01

    Nematode acetylcholine (ACh) receptors were characterized using both biochemical and electrophysiological techniques, including: (1) receptor binding studies in crude homogenates of the free-living nematode Caenorhabditis elegans and the parasitic nematode Ascaris lumbricoides with the high-affinity probe ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) which binds to muscarinic receptors in many vertebrate and invertebrate tissues (2) measurement of depolarization and contraction induced by a variety of cholinergic agents, including N-methylscopolamine (NMS), in an innervated dorsal muscle strip preparation of Ascaris; (3) examination of the antagonistic actions of d-tubocurarine (dTC) and NMS at dorsal neuromuscular junction; (4) measurement of input resistance changes in Ascaris commissural motorneurons induced by ACh, dTC, NMS, pilocarpine and other cholinergic drugs.

  3. European Integration and Outward FDI from Central and Eastern Europe

    DEFF Research Database (Denmark)

    Jindra, B.; Hassan, S. S.; Gunther, J.;

    2015-01-01

    The European Union (EU) Member States in central and eastern Europe (CEE) witnessed a surge in outward foreign direct investment (OFDI) between 2000 and the start of the global financial crisis. This article investigates whether the European integration process altered the relative importance of ...

  4. Central system of Interlock of ITER, high integrity architecture

    International Nuclear Information System (INIS)

    The CIS (Central Interlock System), along with the CODAC system and CSS (Central Safety System), form the central I and C systems of ITER. The CIS is responsible for implementing the core functions of protection (Central Interlock Functions) through different systems of plant (Plant Systems) within the overall strategy of investment protection for ITER. IBERDROLA supports engineering to define and develop the control architecture of CIS according to the stringent requirements of integrity, availability and response time. For functions with response times of the order of half a second is selected PLC High availability of industrial range. However, due to the nature of the machine itself, certain functions must be able to act under the millisecond, so it has had to develop a solution based on FPGA (Field Programmable Gate Array) capable of meeting the requirements architecture. In this article CIS architecture is described, as well as the process for the development and validation of the selected platforms. (Author)

  5. Affect integration and reflective function: clarification of central conceptual issues.

    Science.gov (United States)

    Solbakken, Ole André; Hansen, Roger Sandvik; Monsen, Jon Trygve

    2011-07-01

    The importance of affect regulation, modulation or integration for higher-order reflection and adequate functioning is increasingly emphasized across different therapeutic approaches and theories of change. These processes are probably central to any psychotherapeutic endeavor, whether explicitly conceptualized or not, and in recent years a number of therapeutic approaches have been developed that explicitly target them as a primary area of change. However, there still is important lack of clarity in the field regarding the understanding and operationalization of affect integration, particularly when it comes to specifying underlying mechanisms, the significance of different affect states, and the establishment of operational criteria for measurement. The conceptual relationship between affect integration and reflective function thus remains ambiguous. The present article addresses these topics, indicating ways in which a more complex and exhaustive understanding of integration of affect, cognition and behavior can be attained.

  6. [Cholinergic system of the heart].

    Science.gov (United States)

    Kučera, Matej; Hrabovská, Anna

    2015-12-01

    The cholinergic system of the heart can be either of neuronal or non-neuronal origin. The neuronal cholinergic system in the heart is represented by preganglionic parasympathetic pathways, intracardiac parasympathetic ganglia and postganglionic parasympathetic neurons projecting to the atria, SA node and AV node. The non-neuronal cholinergic system consists of cardiomyocytes that have complete equipment for synthesis and secretion of acetylcholine. Current knowledge suggests that the non-neuronal cholinergic system in the heart affects the regulation of the heart during sympathetic activation. The non-neuronal cholinergic system of the heart plays also a role in the energy metabolism of cardimyocites. Acetylcholine of both neuronal and non-neuronal origin acts in the heart through muscarinic and nicotinic receptors. The effect of acetylcholine in the heart is terminated by cholinesterases acetylcholinesterase and butyrylcholinesterase. Recently, papers suggest that the increased cholinergic tone in the heart by cholinesterase inhibitors has a positive effect on some cardiovascular disorders such as heart failure. For this reason, the cholinesterase inhibitors might be used in the treatment of certain cardiovascular disorders in the future.

  7. Cholinergic Targets in Lung Cancer.

    Science.gov (United States)

    Spindel, Eliot R

    2016-01-01

    Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because activation of mAChR and nAChR stimulates growth; tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from distal sources and from nicotine in the high percentage of lung cancer patients who are smokers. The stimulation of lung cancer growth by cholinergic agonists offers many potential new targets for lung cancer therapy. Cholinergic signaling can be targeted at the level of choline transport; acetylcholine synthesis, secretion and degradation; and nicotinic and muscarinic receptors. In addition, the newly describe family of ly-6 allosteric modulators of nicotinic signaling such as lynx1 and lynx2 offers yet another new approach to novel lung cancer therapeutics. Each of these targets has their potential advantages and disadvantages for the development of new lung cancer therapies which are discussed in this review. PMID:26818857

  8. Cholinergic modulation of event-related oscillations (ERO).

    Science.gov (United States)

    Sanchez-Alavez, Manuel; Robledo, Patricia; Wills, Derek N; Havstad, James; Ehlers, Cindy L

    2014-04-22

    The cholinergic system in the brain modulates patterns of activity involved in general arousal, attention processing, memory and consciousness. In the present study we determined the effects of selective cholinergic lesions of the medial septum area (MS) or nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs). A time-frequency based representation was used to determine ERO energy, phase synchronization across trials, recorded within a structure (phase lock index, PLI), and phase synchronization across trials, recorded between brain structures (phase difference lock index, PDLI), in the frontal cortex (Fctx), dorsal hippocampus (DHPC) and central amygdala (Amyg). Lesions in MS produced: (1) decreases in ERO energy in delta, theta, alpha, beta and gamma frequencies in Amyg, (2) reductions in gamma ERO energy and PLI in Fctx, (3) decreases in PDLI between the Fctx-Amyg in the theta, alpha, beta and gamma frequencies, and (4) decreases in PDLI between the DHPC-Amyg and Fctx-DHPC in the theta frequency bands. Lesions in NBM resulted in: (1) increased ERO energy in delta and theta frequency bands in Fctx, (2) reduced gamma ERO energy in Fctx and Amyg, (3) reductions in PLI in the theta, beta and gamma frequency ranges in Fctx, (4) reductions in gamma PLI in DHPC and (5) reduced beta PLI in Amyg. These studies suggest that the MS cholinergic system can alter phase synchronization between brain areas whereas the NBM cholinergic system modifies phase synchronization/phase resetting within a brain area. PMID:24594019

  9. New Etiology of Cholinergic Urticaria.

    Science.gov (United States)

    Tokura, Yoshiki

    2016-01-01

    Cholinergic urticaria (CholU) is characterized by pinpoint-sized, highly pruritic wheals occurring upon sweating. Both direct and indirect theories in the interaction of acetylcholine (ACh) with mast cells have been put forward in the sweating-associated histamine release from mast cells. In the mechanism of indirect involvement of ACh, patients are hypersensitive to sweat antigen(s) and develop wheals in response to sweat substances leaking from the syringeal ducts to the dermis, possibly by obstruction of the ducts. Some patients with CholU exhibit a positive reaction to intradermal injection of their own diluted sweat, representing 'sweat allergy (hypersensitivity)'. Regarding the direct interaction theory between ACh and mast cells, we found that CholU with anhidrosis and hypohidrosis lacks cholinergic receptor M3 (CHRM3) expression in eccrine sweat gland epithelial cells. The expression of CHRM3 is completely absent in the anhidrotic areas and lowly expressed in the hypohidrotic areas. In the hypohidrotic area, where CholU occurs, it is hypothesized that ACh released from nerves cannot be completely trapped by cholinergic receptors of eccrine glands and overflows to the adjacent mast cells, leading to wheals. PMID:27584968

  10. Higher sensitivity to cadmium induced cell death of basal forebrain cholinergic neurons: A cholinesterase dependent mechanism

    International Nuclear Information System (INIS)

    Cadmium is an environmental pollutant, which is a cause of concern because it can be greatly concentrated in the organism causing severe damage to a variety of organs including the nervous system which is one of the most affected. Cadmium has been reported to produce learning and memory dysfunctions and Alzheimer like symptoms, though the mechanism is unknown. On the other hand, cholinergic system in central nervous system (CNS) is implicated on learning and memory regulation, and it has been reported that cadmium can affect cholinergic transmission and it can also induce selective toxicity on cholinergic system at peripheral level, producing cholinergic neurons loss, which may explain cadmium effects on learning and memory processes if produced on central level. The present study is aimed at researching the selective neurotoxicity induced by cadmium on cholinergic system in CNS. For this purpose we evaluated, in basal forebrain region, the cadmium toxic effects on neuronal viability and the cholinergic mechanisms related to it on NS56 cholinergic mourine septal cell line. This study proves that cadmium induces a more pronounced, but not selective, cell death on acetylcholinesterase (AChE) on cholinergic neurons. Moreover, MTT and LDH assays showed a dose dependent decrease of cell viability in NS56 cells. The ACh treatment of SN56 cells did not revert cell viability reduction induced by cadmium, but siRNA transfection against AChE partially reduced it. Our present results provide new understanding of the mechanisms contributing to the harmful effects of cadmium on the function and viability of neurons, and the possible relevance of cadmium in the pathogenesis of neurodegenerative diseases

  11. The Brown-Henneaux's central charge from the path-integral boundary condition

    OpenAIRE

    Terashima, Hiroaki

    2000-01-01

    We derive Brown-Henneaux's commutation relation and central charge in the framework of the path integral. If we use the leading part of the asymptotic symmetry to derive the Ward-Takahashi identity, we can see the central charge arises from the fact that the boundary condition of the path integral is not invariant under the transformation.

  12. Evaluating the evidence surrounding pontine cholinergic involvement in REM sleep generation

    Directory of Open Access Journals (Sweden)

    Kevin P Grace

    2015-09-01

    Full Text Available Rapid eye movement (REM sleep - characterized by vivid dreaming, motor paralysis, and heightened neural activity - is one of the fundamental states of the mammalian central nervous system. Initial theories of rapid eye movement (REM sleep generation posited that induction of the state required activation of the ‘pontine REM sleep generator’ by cholinergic inputs. Here we review and evaluate the evidence surrounding cholinergic involvement in REM sleep generation. We submit that: (i the capacity of pontine cholinergic neurotransmission to generate REM sleep has been firmly established by gain-of-function experiments, (ii the function of endogenous cholinergic input to REM sleep generating sites cannot be determined by gain-of-function experiments; rather, loss-of-function studies are required, (iii loss-of-function studies show that endogenous cholinergic input to the PFT is not required for REM sleep generation, and (iv Cholinergic input to the pontine REM sleep generating sites serve an accessory role in REM sleep generation: reinforcing non-REM-to-REM sleep transitions making them quicker and less likely to fail.

  13. Evaluating the Evidence Surrounding Pontine Cholinergic Involvement in REM Sleep Generation.

    Science.gov (United States)

    Grace, Kevin P; Horner, Richard L

    2015-01-01

    Rapid eye movement (REM) sleep - characterized by vivid dreaming, motor paralysis, and heightened neural activity - is one of the fundamental states of the mammalian central nervous system. Initial theories of REM sleep generation posited that induction of the state required activation of the "pontine REM sleep generator" by cholinergic inputs. Here, we review and evaluate the evidence surrounding cholinergic involvement in REM sleep generation. We submit that: (i) the capacity of pontine cholinergic neurotransmission to generate REM sleep has been firmly established by gain-of-function experiments, (ii) the function of endogenous cholinergic input to REM sleep generating sites cannot be determined by gain-of-function experiments; rather, loss-of-function studies are required, (iii) loss-of-function studies show that endogenous cholinergic input to the PTF is not required for REM sleep generation, and (iv) cholinergic input to the pontine REM sleep generating sites serve an accessory role in REM sleep generation: reinforcing non-REM-to-REM sleep transitions making them quicker and less likely to fail.

  14. Integral power evaluation in fossil fuel power plants; Evaluacion energetica integral en unidades de centrales termoelectricas

    Energy Technology Data Exchange (ETDEWEB)

    Figueroa I, Luis R; Sanchez H, Laura E; Rodriguez M, Jose H [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico); Nebradt G, Jesus [Unidad de Investigacion y Desarrollo de la Subdireccion de Generacion de la Comision Federal de Electricidad, (Mexico)

    2006-07-01

    In this occasion, a methodology is presented that carries out an integral energy evaluation of fossil fuel power plants units (FFPPU) with the purpose of determining the root of the significant decrements of power produced soon after the annual maintenance service. This proposal, besides identifying the origin of the energy efficiency problems, offers information about the contributions of each one of the involved equipment in the total decrement of the unit. With this methodology, the maintenance focuses in the equipment that contributes to the greater energy loss. This document presents such methodology along with its application in a real case, results and necessary remedial actions, demonstrating that its application offers bases for the investment in corrective measures. [Spanish] En esta ocasion se presenta una metodologia que efectua una evaluacion energetica integral de las unidades de centrales termoelectricas (UCT) con el fin de determinar la raiz de los decrementos de potencia significativos producidos luego del servicio anual de mantenimiento. Dicha propuesta, ademas de identificar el origen de los problemas de eficiencia energetica, brinda informacion acerca de las aportaciones de cada uno de los equipos involucrados al decremento total de la unidad. Con esta metodologia, el mantenimiento se enfoca a los equipos que contribuyen a la mayor perdida de potencia. Este documento exhibe tal metodologia junto con su aplicacion en un caso real, resultados y las acciones correctivas necesarias, demostrando que su aplicacion ofrece bases para una inversion futura en medidas correctivas.

  15. Central limit theorems for multiple stochastic integrals and Malliavin calculus

    OpenAIRE

    Nualart, David; Ortiz, Salvador

    2007-01-01

    We give a new characterization for the convergence in distribution to a standard normal law of a sequence of multiple stochastic integrals of a fixed order with variance one, in terms of the Malliavin derivatives of the sequence. We extend our result to the multidimensional case and prove a weak convergence result for a sequence of square integrable random variables.

  16. Evaluating Computer Technology Integration in a Centralized School System

    Science.gov (United States)

    Eteokleous, N.

    2008-01-01

    The study evaluated the current situation in Cyprus elementary classrooms regarding computer technology integration in an attempt to identify ways of expanding teachers' and students' experiences with computer technology. It examined how Cypriot elementary teachers use computers, and the factors that influence computer integration in their…

  17. PET study of cholinergic system in the brain

    International Nuclear Information System (INIS)

    Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant ''k 3'' as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/ 3/ 8/ 10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/ 3/ 8/ 38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer's disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson's disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supra nuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neuro degenerative disorders with dementia. (author)

  18. PET study of cholinergic system in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Shinotoh, Hitoshi [Chiba Univ. (Japan). School of Medicine

    1999-01-01

    Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant ``k 3`` as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/ 3/ 8/ 10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/ 3/ 8/ 38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer`s disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson`s disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supra nuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neuro degenerative disorders with dementia. (author)

  19. Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.

    Directory of Open Access Journals (Sweden)

    Adam S Hamlin

    Full Text Available Loss of integrity of the basal forebrain cholinergic neurons is a consistent feature of Alzheimer's disease, and measurement of basal forebrain degeneration by magnetic resonance imaging is emerging as a sensitive diagnostic marker for prodromal disease. It is also known that Alzheimer's disease patients perform poorly on both real space and computerized cued (allothetic or uncued (idiothetic recall navigation tasks. Although the hippocampus is required for allothetic navigation, lesions of this region only mildly affect idiothetic navigation. Here we tested the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Basal forebrain cholinergic neurons were selectively lesioned in mice using the toxin saporin conjugated to a basal forebrain cholinergic neuronal marker, the p75 neurotrophin receptor. Control animals were able to learn and remember spatial information when tested on a modified version of the passive place avoidance test where all extramaze cues were removed, and animals had to rely on idiothetic signals. However, the exploratory behaviour of mice with cholinergic basal forebrain lesions was highly disorganized during this test. By contrast, the lesioned animals performed no differently from controls in tasks involving contextual fear conditioning and spatial working memory (Y maze, and displayed no deficits in potentially confounding behaviours such as motor performance, anxiety, or disturbed sleep/wake cycles. These data suggest that the basal forebrain cholinergic system plays a specific role in idiothetic navigation, a modality that is impaired early in Alzheimer's disease.

  20. A case of postganglionic cholinergic dysautonomia.

    OpenAIRE

    Takayama, H; Kazahaya, Y; Kashihara, N.; Kuroda, H.; Miyawaki, S; Ota, Z; Ogawa, N.

    1987-01-01

    A 24 year old female presented with signs and symptoms of postganglionic cholinergic autonomic dysfunction manifested by impaired lachrymation and salivation, mydriasis of the pupil, decreased gastrointestinal motility, atony of the bladder, and sweating and taste disturbance. Clinical and pharmacological studies confirmed that the abnormalities were restricted mainly to the postganglionic cholinergic autonomic systems. The titre of serum complement was low, antinuclear antibodies revealed a ...

  1. Illuminating the role of cholinergic signaling in circuits of attention and emotionally salient behaviors

    Directory of Open Access Journals (Sweden)

    Antonio eLuchicchi

    2014-10-01

    Full Text Available Acetylcholine (ACh signaling underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. Alterations in ACh signaling are involved in the pathophysiology of multiple neuropsychiatric disorders. In the central nervous system, ACh transmission is mainly guaranteed by dense innervation of select cortical and subcortical regions from disperse groups of cholinergic neurons within the basal forebrain (e.g. diagonal band, medial septal, nucleus basalis and the pontine-mesencephalic nuclei, respectively. Despite the fundamental role of cholinergic signaling in the CNS and the long standing knowledge of the organization of cholinergic circuitry, remarkably little is known about precisely how ACh release modulates cortical and subcortical neural activity and the behaviors these circuits subserve. Growing interest in cholinergic signaling in the CNS focuses on the mechanism(s of action by which endogenously released ACh regulates cognitive functions, acting as a neuromodulator and /or as a direct transmitter via nicotinic and muscarinic receptors. The development of optogenetic techniques has provided a valuable toolbox with which we can address these questions, as it allows the selective manipulation of the excitability of cholinergic inputs to the diverse array of cholinergic target fields within cortical and subcortical domains. Here, we review recent papers that use the light-sensitive opsins in the cholinergic system to elucidate the role of ACh in circuits related to attention and emotionally salient behaviors. In particular, we highlight recent optogenetic studies which have tried to disentangle the precise role of ACh in the modulation of cortical-, hippocampal- and striatal-dependent functions.

  2. Some aspects of integrated water resources management in central Asia

    Science.gov (United States)

    Khaydarova, V.; Penkova, N.; Pak, E.; Poberejsky, L.; Beltrao, J.

    2003-04-01

    Two main tasks are to be implemented for elaboration of the governmental water distribution criteria in Central Asia: 1 -development of the common methodological basis for the intergovernmental water distribution; and 2 - to reopen and continue both theoretical and experimental researches of various aspects of the wastewater reuse. The prospects of socio economic development of all Central Asian countries are substantially defined by the water resources availability. The water resources of Central Asia belong, mainly, watersheds of the Syr-Darya and Amu Darya rivers. The basic flow of Amu Darya is formed in territory of Tajikistan. Then the Amu Darya river proceeds along border of Afghanistan with Uzbekistan, crosses Turkmenistan and again comes back to Uzbekistan and then runs into the Aral Sea. The Syr-Darya is second river on the water discharge and is first river on length in Central Asia. The basic flow of Syr Darya is formed in territory of Kyrgyzstan. Then the Syr-Darya river crosses of Uzbekistan and Tajikistan and runs into the Aral Sea in territory of Kazakhstan. During the Soviet Union the water resources of two river watersheds were divided among the Central Asian republics on the basis of the general plans developed by the center in Moscow. In the beginning of 90s years, after taking of sovereignty by the former Soviet republics, the unified control system of water resources management was abolished and the various approaches to its transformation caused by features of the national economy developing, elected models of transition from command to market mechanisms of economic activity, and also specificity of political and social processes in each of the states of region were planned. The distinctions of modern priorities of economic development of the states of region have generated the contradiction of interests in the intergovernmental water distribution that can in the long term become complicated even more in connection with the increasing of water

  3. Indico central - events organisation, ergonomics and collaboration tools integration

    Science.gov (United States)

    Benito Gonzélez López, José; Ferreira, José Pedro; Baron, Thomas

    2010-04-01

    While the remote collaboration services at CERN slowly aggregate around the Indico event management software, its new version which is the result of a careful maturation process includes improvements which will set a new reference in its domain. The presentation will focus on the description of the new features of the tool, the user feedback process which resulted in a new record of usability. We will also describe the interactions with the worldwide community of users and server administrators and the impact this has had on our development process, as well as the tools set in place to streamline the work between the different collaborating sites. A last part will be dedicated to the use of Indico as a central hub for operating other local services around the event organisation (registration epayment, audiovisual recording, webcast, room booking, and videoconference support)

  4. Indico Central - Events Organisation, Ergonomics and Collaboration Tools Integration

    CERN Document Server

    Gonzalez Lopez, J B; Baron, T; CERN. Geneva. IT Department

    2010-01-01

    While the remote collaboration services at CERN slowly aggregate around the Indico event management software, its new version which is the result of a careful maturation process includes improvements which will set a new reference in its domain. The presentation will focus on the description of the new features of the tool, the user feedback process which resulted in a new record of usability. We will also describe the interactions with the worldwide community of users and server administrators and the impact this has had on our development process, as well as the tools set in place to streamline the work between the different collaborating sites. A last part will be dedicated to the use of Indico as a central hub for operating other local services around the event organisation (registration epayment, audiovisual recording, webcast, room booking, and videoconference support)

  5. Cholinergic enhancement reduces orientation-specific surround suppression but not visual crowding

    Directory of Open Access Journals (Sweden)

    Anna A. Kosovicheva

    2012-09-01

    Full Text Available Acetylcholine (ACh reduces the spatial spread of excitatory fMRI responses in early visual cortex and the receptive field sizes of V1 neurons. We investigated the perceptual consequences of these physiological effects of ACh with surround suppression and crowding, two tasks that involve spatial interactions between visual field locations. Surround suppression refers to the reduction in perceived stimulus contrast by a high-contrast surround stimulus. For grating stimuli, surround suppression is selective for the relative orientations of the center and surround, suggesting that it results from inhibitory interactions in early visual cortex. Crowding refers to impaired identification of a peripheral stimulus in the presence of flankers and is thought to result from excessive integration of visual features. We increased synaptic ACh levels by administering the cholinesterase inhibitor donepezil to healthy human subjects in a placebo-controlled, double-blind design. In Exp. 1, we measured surround suppression of a central grating using a contrast discrimination task with three conditions: 1 surround grating with the same orientation as the center (parallel, 2 surround orthogonal to the center, or 3 no surround. Contrast discrimination thresholds were higher in the parallel than in the orthogonal condition, demonstrating orientation-specific surround suppression (OSSS. Cholinergic enhancement reduced thresholds only in the parallel condition, thereby reducing OSSS. In Exp. 2, subjects performed a crowding task in which they reported the identity of a peripheral letter flanked by letters on either side. We measured the critical spacing between the target and flanking letters that allowed reliable identification. Cholinergic enhancement had no effect on critical spacing. Our findings suggest that ACh reduces spatial interactions in tasks involving segmentation of visual field locations but that these effects may be limited to early visual cortical

  6. Cholinergic enhancement reduces orientation-specific surround suppression but not visual crowding.

    Science.gov (United States)

    Kosovicheva, Anna A; Sheremata, Summer L; Rokem, Ariel; Landau, Ayelet N; Silver, Michael A

    2012-01-01

    Acetylcholine (ACh) reduces the spatial spread of excitatory fMRI responses in early visual cortex and receptive field size of V1 neurons. We investigated the perceptual consequences of these physiological effects of ACh with surround suppression and crowding, two phenomena that involve spatial interactions between visual field locations. Surround suppression refers to the reduction in perceived stimulus contrast by a high-contrast surround stimulus. For grating stimuli, surround suppression is selective for the relative orientations of the center and surround, suggesting that it results from inhibitory interactions in early visual cortex. Crowding refers to impaired identification of a peripheral stimulus in the presence of flankers and is thought to result from excessive integration of visual features. We increased synaptic ACh levels by administering the cholinesterase inhibitor donepezil to healthy human subjects in a placebo-controlled, double-blind design. In Experiment 1, we measured surround suppression of a central grating using a contrast discrimination task with three conditions: (1) surround grating with the same orientation as the center (parallel), (2) surround orthogonal to the center, or (3) no surround. Contrast discrimination thresholds were higher in the parallel than in the orthogonal condition, demonstrating orientation-specific surround suppression (OSSS). Cholinergic enhancement decreased thresholds only in the parallel condition, thereby reducing OSSS. In Experiment 2, subjects performed a crowding task in which they reported the identity of a peripheral letter flanked by letters on either side. We measured the critical spacing between the targets and flanking letters that allowed reliable identification. Cholinergic enhancement with donepezil had no effect on critical spacing. Our findings suggest that ACh reduces spatial interactions in tasks involving segmentation of visual field locations but that these effects may be limited to early

  7. Cholinergic regulation of the vasopressin neuroendocrine system

    Energy Technology Data Exchange (ETDEWEB)

    Michels, K.M.

    1987-01-01

    To clarify the physical and functional relationship between the cholinergic system, and the neurodocrine cells of the supraoptic nucleus, a combination of experiments on receptor binding, localization and function were carried out. The putative nicotinic receptor probe (/sup 125/I)alpha bungarotoxin ((/sup 125/I)alpha BTX) bound with high affinity and specificity to the vasopressin and oxytocin magnocellular neurons of the supraoptic nucleus, nucleus circularis, and paraventricular nucleus. Binding of (/sup 125/I)alpha BTX within the neural lobe was very low. In contrast, the muscarinic cholinergic receptor probe (/sup 3/H)quinuclidinylbenzilate ((/sup 3/H)QNB) did not bind to magnocellular vasopressin and oxytocin cell groups. The median eminence, which contains the neurosecretory axons, and the neural lobe of the pituitary contain low levels of (/sup 3/H)QNB binding. The physiological significance of these cholinergic receptors in regulation of vasopressin release was tested using an in vitro preparation of the supraoptic - neural lobe system.

  8. Rabbit Forebrain cholinergic system : Morphological characterization of nuclei and distribution of cholinergic terminals in the cerebral cortex and hippocampus

    NARCIS (Netherlands)

    Varga, C; Hartig, W; Grosche, J; Luiten, PGM; Seeger, J; Brauer, K; Harkany, T; Härtig, Wolfgang; Keijser, Jan N.

    2003-01-01

    Although the rabbit brain, in particular the basal forebrain cholinergic system, has become a common model for neuropathological changes associated with Alzheimer's disease, detailed neuroanatomical studies on the morphological organization of basal forebrain cholinergic nuclei and on their output p

  9. The cholinergic system, circadian rhythmicity, and time memory

    NARCIS (Netherlands)

    Hut, R. A.; Van der Zee, E. A.

    2011-01-01

    This review provides an overview of the interaction between the mammalian cholinergic system and circadian system, and its possible role in time memory. Several studies made clear that circadian (daily) fluctuations in acetylcholine (ACh) release, cholinergic enzyme activity and cholinergic receptor

  10. TIMING IS EVERYTHING, EVEN FOR CHOLINERGIC CONTROL

    OpenAIRE

    Berg, Darwin K.

    2011-01-01

    Synaptic plasticity is widely considered to be a cellular mechanism underlying learning and memory. In this issue of Neuron, Gu and Yakel show that the precise timing of a single cholinergic pulse of activity can determine whether plasticity will occur at a glutamatergic synapse and confer long-term potentiation versus depression.

  11. Cholinergic imaging in dementia spectrum disorders.

    Science.gov (United States)

    Roy, Roman; Niccolini, Flavia; Pagano, Gennaro; Politis, Marios

    2016-07-01

    The multifaceted nature of the pathology of dementia spectrum disorders has complicated their management and the development of effective treatments. This is despite the fact that they are far from uncommon, with Alzheimer's disease (AD) alone affecting 35 million people worldwide. The cholinergic system has been found to be crucially involved in cognitive function, with cholinergic dysfunction playing a pivotal role in the pathophysiology of dementia. The use of molecular imaging such as SPECT and PET for tagging targets within the cholinergic system has shown promise for elucidating key aspects of underlying pathology in dementia spectrum disorders, including AD or parkinsonian dementias. SPECT and PET studies using selective radioligands for cholinergic markers, such as [(11)C]MP4A and [(11)C]PMP PET for acetylcholinesterase (AChE), [(123)I]5IA SPECT for the α4β2 nicotinic acetylcholine receptor and [(123)I]IBVM SPECT for the vesicular acetylcholine transporter, have been developed in an attempt to clarify those aspects of the diseases that remain unclear. This has led to a variety of findings, such as cortical AChE being significantly reduced in Parkinson's disease (PD), PD with dementia (PDD) and AD, as well as correlating with certain aspects of cognitive function such as attention and working memory. Thalamic AChE is significantly reduced in progressive supranuclear palsy (PSP) and multiple system atrophy, whilst it is not affected in PD. Some of these findings have brought about suggestions for the improvement of clinical practice, such as the use of a thalamic/cortical AChE ratio to differentiate between PD and PSP, two diseases that could overlap in terms of initial clinical presentation. Here, we review the findings from molecular imaging studies that have investigated the role of the cholinergic system in dementia spectrum disorders. PMID:26984612

  12. Cholinergic imaging in dementia spectrum disorders

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Roman; Niccolini, Flavia; Pagano, Gennaro; Politis, Marios [Institute of Psychiatry, Psychology and Neuroscience, King' s College London, Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, London (United Kingdom)

    2016-07-15

    The multifaceted nature of the pathology of dementia spectrum disorders has complicated their management and the development of effective treatments. This is despite the fact that they are far from uncommon, with Alzheimer's disease (AD) alone affecting 35 million people worldwide. The cholinergic system has been found to be crucially involved in cognitive function, with cholinergic dysfunction playing a pivotal role in the pathophysiology of dementia. The use of molecular imaging such as SPECT and PET for tagging targets within the cholinergic system has shown promise for elucidating key aspects of underlying pathology in dementia spectrum disorders, including AD or parkinsonian dementias. SPECT and PET studies using selective radioligands for cholinergic markers, such as [{sup 11}C]MP4A and [{sup 11}C]PMP PET for acetylcholinesterase (AChE), [{sup 123}I]5IA SPECT for the α{sub 4}β{sub 2} nicotinic acetylcholine receptor and [{sup 123}I]IBVM SPECT for the vesicular acetylcholine transporter, have been developed in an attempt to clarify those aspects of the diseases that remain unclear. This has led to a variety of findings, such as cortical AChE being significantly reduced in Parkinson's disease (PD), PD with dementia (PDD) and AD, as well as correlating with certain aspects of cognitive function such as attention and working memory. Thalamic AChE is significantly reduced in progressive supranuclear palsy (PSP) and multiple system atrophy, whilst it is not affected in PD. Some of these findings have brought about suggestions for the improvement of clinical practice, such as the use of a thalamic/cortical AChE ratio to differentiate between PD and PSP, two diseases that could overlap in terms of initial clinical presentation. Here, we review the findings from molecular imaging studies that have investigated the role of the cholinergic system in dementia spectrum disorders. (orig.)

  13. Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model.

    Science.gov (United States)

    Kerbler, Georg M; Hamlin, Adam S; Pannek, Kerstin; Kurniawan, Nyoman D; Keller, Marianne D; Rose, Stephen E; Coulson, Elizabeth J

    2013-02-01

    tractography parameters of the basal forebrain tracts. These findings provide increased support for using DTI and probabilistic tractography as non-invasive tools for diagnosing and/or monitoring the progression of conditions affecting the integrity of the basal forebrain cholinergic system in humans, including Alzheimer's disease. PMID:23128077

  14. Effects of Tiantai Ⅰ on the activity of central cholinergic system in mice with spontaneous Alzheimer disease%天泰1号对自发老年性痴呆模型中枢胆碱能系统活性的影响

    Institute of Scientific and Technical Information of China (English)

    吴正治; 李明; 李耀芳; 贾秀琴; 张永锋

    2006-01-01

    BACKGROUND: Tiantai I consists of gastrodia, Chinese angelica root, areca seed. It has been considered as the roles of invigorating the liver, nourishing marrow, heightening the intelligence and causing resuscitation. OBJECTIVE: To observe the effects of Tiantai Ⅰ on the abilities of learn ing and memory and the activity of central cholinergic system in mice with spontaneous Alzheimer disease. DESIGN: A randomized control observation. SETTING: Shenzhen Institute of Integrated Chinese and Western Medicine. MATERIALS: Male Kunming mice of 13 months old were raised to 21 months old, of which 52 with spontaneous Alzheimer disease were screened. They were randomly divided into blank control group, western drug control group, Tiantai Ⅰ 6.80 and 20.41 g/kg groups, 13 mice in each group. Another 13 aged mice with normal learning and memory abilities were selected as the normal control group at the same time. METHODS: Mice in the western drug control group were treated with 0.6 mg/Kg Hydergine, those in the Tiantai Ⅰ 6.80 and 20.41 g/kg groups were given intragastric administration of Tiantai Ⅰ of 6.80 and 20.41 g/kg, respectively, and those in the normal control group and blank control group were given double distilled water of the same volume. The learning and memory results were examined by the step-down test. Freezing sections of brain tissue were prepared, acetylcholinesterase (AChE) fiber was showed according to the Hedreen method, and choline acetyltransferase (ChAT) was detected with Burt and Silver methods, the automatic image analysis system for biomedical application was applied in the quantitative analysis of AChE fiber and ChAT activity. MAIN OUTCOME MEASURES: ① Effect of Tiantai Ⅰ on the abilities of learning and memory in mice with Alzheimer disease; ② AChE fiber area density in temporal cortex and hippocampal CA1 region; ③ ChAT ac tivity in Meynert nuclei of basal forebrain. RESULTS: ① Tiantai Ⅰ in ameliorating the abilities of learning

  15. A framework for integrating heterogeneous clinical data for a disease area into a central data warehouse.

    Science.gov (United States)

    Karmen, Christian; Ganzinger, Matthias; Kohl, Christian D; Firnkorn, Daniel; Knaup-Gregori, Petra

    2014-01-01

    Structured collection of clinical facts is a common approach in clinical research. Especially in the analysis of rare diseases it is often necessary to aggregate study data from several sites in order to achieve a statistically significant cohort size. In this paper we describe a framework how to approach an integration of heterogeneous clinical data into a central register. This enables site-spanning queries for the occurrence of specific clinical facts and thus supports clinical research. The framework consists of three sequential steps, starting from a formal data harmonization process, to the data transformation methods and finally the integration into a proper data warehouse. We implemented reusable software templates that are based on our best practices in several projects in integrating heterogeneous clinical data. Our methods potentially increase the efficiency and quality for future data integration projects by reducing the implementation effort as well as the project management effort by usage of our approaches as a guideline.

  16. Case study: centralized wastewater treatment plant at Rawang Integrated Industrial Park

    International Nuclear Information System (INIS)

    Survey has been conducted at Rawang Integrated Industrial Park (RIIP) to investigate the possibility of setting up centralized industrial wastewater treatment plant. Rawang integrated industrial park is selected based on suggestion from department of environment. RIIP consists of about 150 industries with various type of activities operated in the area. Only 9 out of estimated 150 industries have individual wastewater treatment plant. The business activities of the 9 industries include food processing, textile, welding rods manufacturing, steel galvanizing and battery manufacturing. Wastewater generated by the industries are characterized by high oil and grease, cod, bod, organic matter, metal hydroxide and acidic. Besides that most of industries do the monitoring only once a month. This paper will also discuss the advantages of setting up of centralized industrial wastewater treatment plant to the government authorities, industries, people and environment. (Author)

  17. A Regional GIS of the Central Andes, South America - Integration of Satellite and Geophysical Data Sets

    OpenAIRE

    Hofmann, K; F. K. List;  

    1996-01-01

    The Central Andes of northern Chile, southwestern Bolivia and northwestern Argentina are studied by a research project supported by the Deutsche Forschungsgemeinschaft (SFB 267). The main topics of these geological and geophysical investigations are the orogeny of the Andean mountains and the crustal development at an active continental margin. The "Andean GIS" is designed as a tool for data collection, management, overview, analysis and mapping. The integration of different data supports the...

  18. Functional Integration between Salience and Central Executive Networks: A Role for Action Video Game Experience

    OpenAIRE

    Diankun Gong; Hui He; Weiyi Ma; Dongbo Liu; Mengting Huang; Li Dong; Jinnan Gong; Jianfu Li; Cheng Luo; Dezhong Yao

    2016-01-01

    Action video games (AVGs) have attracted increasing research attention as they offer a unique perspective into the relation between active learning and neural plasticity. However, little research has examined the relation between AVG experience and the plasticity of neural network mechanisms. It has been proposed that AVG experience is related to the integration between Salience Network (SN) and Central Executive Network (CEN), which are responsible for attention and working memory, respectiv...

  19. Cholinergic Mechanisms in Spinal Locomotion - Potential Target for Rehabilitation Approaches

    Directory of Open Access Journals (Sweden)

    L M Jordan

    2014-11-01

    Full Text Available Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a hyper-cholinergic state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in supressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed

  20. Cholinergic Circuit Control of Postnatal Neurogenesis

    Science.gov (United States)

    Asrican, Brent; Paez-Gonzalez, Patricia; Erb, Joshua; Kuo, Chay T.

    2016-01-01

    New neuron addition via continued neurogenesis in the postnatal/adult mammalian brain presents a distinct form of nervous system plasticity. During embryonic development, precise temporal and spatial patterns of neurogenesis are necessary to create the nervous system architecture. Similar between embryonic and postnatal stages, neurogenic proliferation is regulated by neural stem cell (NSC)-intrinsic mechanisms layered upon cues from their local microenvironmental niche. Following developmental assembly, it remains relatively unclear what may be the key driving forces that sustain continued production of neurons in the postnatal/adult brain. Recent experimental evidence suggests that patterned activity from specific neural circuits can also directly govern postnatal/adult neurogenesis. Here, we review experimental findings that revealed cholinergic modulation, and how patterns of neuronal activity and acetylcholine release may differentially or synergistically activate downstream signaling in NSCs. Higher-order excitatory and inhibitory inputs regulating cholinergic neuron firing, and their implications in neurogenesis control are also considered.

  1. Glucocorticoid programming of the mesopontine cholinergic system

    Directory of Open Access Journals (Sweden)

    Sónia eBorges

    2013-12-01

    Full Text Available Stress perception, response, adaptation and coping strategies are individually distinct, and the sequel of stress and/or glucocorticoids is also distinct between subjects. In the last years, it has become clear that early life stress is a powerful modulator of neuroendocrine stress-responsive circuits, programming intrinsic susceptibility to stress, and potentiating the appearance of stress-related disorders such as depression, anxiety and addiction. Herein we were interested in understanding how early life experiences reset the normal processing of negative stimuli, leading to emotional dysfunction. Animals prenatally exposed to glucocorticoids (iuGC present hyperanxiety, increased fear behaviour and hyper-reactivity to negative stimuli. In parallel, we found a remarkable increase in the number of aversive 22kHz ultrasonic vocalizations in response to an aversive cue. Considering the suggested role of the mesopontine tegmentum cholinergic pathway, arising from the laterodorsal tegmental nucleus (LDT and pedunculopontine tegmental nucleus (PPT, in the initiation of 22kHz vocalizations and hypothetically in the control of emotional arousal and tone, we decided to evaluate the condition of this circuit in iuGC animals. Notably, in a basal situation, iuGC animals present increased choline acetyltransferase (ChAT expression in the LDT and PPT, but not in other cholinergic nuclei, namely in the nucleus basalis of Meynert. In addition, and in accordance with the amplified response to an adverse stimulus of iuGC animals, we found marked changes in the cholinergic activation pattern of LDT and PPT regions. Altogether, our results suggest a specific cholinergic pathway programing by prenatal GC, and hint that this may be of relevance in setting individuals stress vulnerability threshold.

  2. NASA LCLUC Program: An Integrated Forest Monitoring System for Central Africa

    Science.gov (United States)

    Laporte, Nadine; LeMoigne, Jacqueline; Elkan, Paul; Desmet, Olivier; Paget, Dominique; Pumptre, Andrew; Gouala, Patrice; Honzack, Miro; Maisels, Fiona

    2004-01-01

    Central Africa has the second largest unfragmented block of tropical rain forest in the world; it is also one of the largest carbon and biodiversity reservoirs. With nearly one-third of the forest currently allocated for logging, the region is poised to undergo extensive land-use change. Through the mapping of the forests, our Integrated Forest Monitoring System for Central Africa (INFORMS) project aims to monitor habitat alteration, support biodiversity conservation, and promote better land-use planning and forest management. Designed as an interdisciplinary project, its goal is to integrate data acquired from satellites with field observations from forest inventories, wildlife surveys, and socio-economic studies to map and monitor forest resources. This project also emphasizes on collaboration and coordination with international, regional, national, and local partners-including non-profit, governmental, and commercial sectors. This project has been focused on developing remote sensing products for the needs of forest conservation and management, insuring that research findings are incorporated in forest management plans at the national level. The societal impact of INFORMS can be also appreciated through the development of a regional remote sensing network in central Africa. With a regional office in Kinshasa, (www.OSFAC.org), the contribution to the development of forest management plans for 1.5 million hectares of forests in northern Republic of Congo (www.tt-timber.com), and the monitoring of park encroachments in the Albertine region (Uganda and DRC) (www.albertinerift.org).

  3. Bar-induced central star formation as revealed by integral field spectroscopy from CALIFA

    CERN Document Server

    Lin, Lin; He, Yanqin; Xiao, Ting; Wang, Enci

    2016-01-01

    We investigate the recent star formation history (SFH) in the inner region of 57 nearly face-on spiral galaxies selected from the Calar Alto Legacy Integral Field Area (CALIFA) survey. For each galaxy we use the integral field spectroscopy from CALIFA to obtain two-dimensional maps and radial profiles of three parameters that are sensitive indicators of the recent SFH: the 4000\\AA\\ break (D$_n$(4000)), and the equivalent width of H$\\delta$ absorption (EW(H$\\delta_A$)) and H$\\alpha$ emission (EW(H$\\alpha$)). We have also performed photometric decomposition of bulge/bar/disk components based on SDSS optical image. We identify a class of 17 "turnover" galaxies whose central region present significant drop in D$_n$(4000), and most of them correspondingly show a central upturn in EW(H$\\delta_A$) and EW(H$\\alpha$). This indicates that the central region of the turnover galaxies has experienced star formation in the past 1-2 Gyr, which makes the bulge younger and more star-forming than surrounding regions. We find a...

  4. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

    OpenAIRE

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

    2015-01-01

    Purpose Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused ...

  5. The Integration of MEPs from Central and Eastern Europe into the European Parliament

    Directory of Open Access Journals (Sweden)

    Radko Hokovský

    2012-04-01

    Full Text Available This article evaluates the level of integration of Members of the European Parliament from Central and Eastern Europe in the European Parliament after the EU enlargements of 2004 and 2007. The main objective is to address the puzzle of how the European Parliament’s political groups could maintain or even increase their voting cohesion after the influx of a significantly large number of new MEPs coming from countries with different historical experience, socio-economic characteristics, and political and party systems. Three indicators of MEP integration are defined: integration into parliamentary leadership, integration into parliamentary work, and integration into voting patterns. The article uses data from the VoteWatch.eu website on MEPs’ activities and voting between the years 2004-2011, as well as data from official documents of the European Parliament and its political groups. Analysis of the data reveals that the new member states’ MEPs were significantly under-represented in parliamentary leadership and key legislative activities, despite the fact that their voting loyalty to their political groups was greater than that of their colleagues from older member states.

  6. Alterations in cholinergic sensitivity of respiratory neurons induced by pre-natal nicotine: a mechanism for respiratory dysfunction in neonatal mice

    OpenAIRE

    Coddou, Claudio; Bravo, Eduardo; Eugenín, Jaime

    2009-01-01

    Nicotine may link cigarette smoking during pregnancy with sudden infant death syndrome (SIDS). Pre-natal nicotine leads to diminished ventilatory responses to hypercarbia and reduced central chemoreception in mice at post-natal days 0–3. We studied how pre-natal nicotine exposure changes the cholinergic contribution to central respiratory chemoreception in neonatal isolated brainstem–spinal cord and slice preparations.

  7. Central limit theorem for integrated square error of kernel estimators of spherical density

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Let X1,…,Xn be iid observations of a random variable X with pr obab ility density function f(x) on the q-dimensional unit sphere Ωq I n Rq+1 ,q≥1. Let fn(x)=n-1 c(h)∑ni=1 K[(1-x′Xi)/ h2]be a kernel estimator of f(x). In this paper we establish a central limit theorem for integrated square error of fn under some mild conditions.

  8. Functional Integration between Salience and Central Executive Networks: A Role for Action Video Game Experience

    Directory of Open Access Journals (Sweden)

    Diankun Gong

    2016-01-01

    Full Text Available Action video games (AVGs have attracted increasing research attention as they offer a unique perspective into the relation between active learning and neural plasticity. However, little research has examined the relation between AVG experience and the plasticity of neural network mechanisms. It has been proposed that AVG experience is related to the integration between Salience Network (SN and Central Executive Network (CEN, which are responsible for attention and working memory, respectively, two cognitive functions essential for AVG playing. This study initiated a systematic investigation of this proposition by analyzing AVG experts’ and amateurs’ resting-state brain functions through graph theoretical analyses and functional connectivity. Results reveal enhanced intra- and internetwork functional integrations in AVG experts compared to amateurs. The findings support the possible relation between AVG experience and the neural network plasticity.

  9. Functional Integration between Salience and Central Executive Networks: A Role for Action Video Game Experience.

    Science.gov (United States)

    Gong, Diankun; He, Hui; Ma, Weiyi; Liu, Dongbo; Huang, Mengting; Dong, Li; Gong, Jinnan; Li, Jianfu; Luo, Cheng; Yao, Dezhong

    2016-01-01

    Action video games (AVGs) have attracted increasing research attention as they offer a unique perspective into the relation between active learning and neural plasticity. However, little research has examined the relation between AVG experience and the plasticity of neural network mechanisms. It has been proposed that AVG experience is related to the integration between Salience Network (SN) and Central Executive Network (CEN), which are responsible for attention and working memory, respectively, two cognitive functions essential for AVG playing. This study initiated a systematic investigation of this proposition by analyzing AVG experts' and amateurs' resting-state brain functions through graph theoretical analyses and functional connectivity. Results reveal enhanced intra- and internetwork functional integrations in AVG experts compared to amateurs. The findings support the possible relation between AVG experience and the neural network plasticity.

  10. Integration of Capital Markets from Central and Eastern Europe: Implications for EU Investors

    Directory of Open Access Journals (Sweden)

    Alexandra HOROBET

    2014-04-01

    Full Text Available Our paper investigates the extent of capital market co-movements between three emerging markets Czech Republic, Hungary and Poland and three developed markets from the European Union – Austria, France and Germany. We test whether an increase in correlations between the six markets took place in recent years, as revealing higher integration of capital markets in the region. We find a statistically significant positive trend in cross-market correlations between 1999 and 2008, before the emergence of the global financial crisis. Movements in national stock markets are not fully synchronized, but increases in market volatilities lead to increases in cross-country correlations. There is a long-term relationship between some of these countries capital markets, and information is transmitted from one market to the other. Our findings confirm previous studies and lead to the conclusion that stock markets from Central and Eastern Europe became more integrated with the developed markets in European Union.

  11. Kinematics of the Central Kiloparsec in Cygnus A from AO Integral Field Spectroscopy

    Science.gov (United States)

    Aylor, Kevin; Rude, G.; Medling, A.; Canalizo, G.; Max, C. E.; Antonucci, R. R.

    2013-01-01

    We present Keck Integral Field Unit observations and long-slit spectroscopy of the central regions of Cygnus A using laser guide star adaptive optics. Our near-IR images show a bi-conic structure clearly seen in Pa-alpha emission and a more flattened structure perpendicular to the axis of the radio jets that is only visible in H_2 emission. Both of these structures are strongly suggestive of an obscuring torus around a heavily extinguished quasar nucleus. We use the integral field spectroscopy to develop velocity maps and model the kinematics of the entire region. We thus set constraints on the torus geometry and obtain an estimate for the mass of the supermassive black hole.

  12. Functional Integration between Salience and Central Executive Networks: A Role for Action Video Game Experience.

    Science.gov (United States)

    Gong, Diankun; He, Hui; Ma, Weiyi; Liu, Dongbo; Huang, Mengting; Dong, Li; Gong, Jinnan; Li, Jianfu; Luo, Cheng; Yao, Dezhong

    2016-01-01

    Action video games (AVGs) have attracted increasing research attention as they offer a unique perspective into the relation between active learning and neural plasticity. However, little research has examined the relation between AVG experience and the plasticity of neural network mechanisms. It has been proposed that AVG experience is related to the integration between Salience Network (SN) and Central Executive Network (CEN), which are responsible for attention and working memory, respectively, two cognitive functions essential for AVG playing. This study initiated a systematic investigation of this proposition by analyzing AVG experts' and amateurs' resting-state brain functions through graph theoretical analyses and functional connectivity. Results reveal enhanced intra- and internetwork functional integrations in AVG experts compared to amateurs. The findings support the possible relation between AVG experience and the neural network plasticity. PMID:26885408

  13. Central American Economic Integration: An Introduction to the Study of Customs Union and Relations with the European Union

    OpenAIRE

    Nieto Solís, José Antonio

    2007-01-01

    This Working Paper focuses on the characteristics and challenges of the process of economic integration in Central America and it analyses the situation and alternatives of the existing customs union in the region. It also refers to the external relations of Central America, in particular with the European Union (EU), the USA (CAFTA) and Mexico (Plan Puebla Panama). In order to extend the analytical scope, Central American relations with the EU have been considered in the general context of t...

  14. Cholinergic degeneration is associated with increased plaque deposition and cognitive impairment in APPswe/PS1dE9 mice

    DEFF Research Database (Denmark)

    Laursen, Bettina; Mørk, Arne; Plath, Niels;

    2013-01-01

    Cholinergic dysfunction and deposition of plaques containing amyloid ß-peptides (Aß) are two of the characteristics of Alzheimer's disease. Here, we combine APPswe/PS1dE9 (APP/PS1) mice with the cholinergic immunotoxin mu p75-saporin (SAP) to integrate partial basal forebrain cholinergic degenera......Cholinergic dysfunction and deposition of plaques containing amyloid ß-peptides (Aß) are two of the characteristics of Alzheimer's disease. Here, we combine APPswe/PS1dE9 (APP/PS1) mice with the cholinergic immunotoxin mu p75-saporin (SAP) to integrate partial basal forebrain cholinergic...... degeneration and the neuropathology of APP/PS1 mice. By 6 months of age, APP/PS1 mice and wild type littermates (Wt) received intracerebroventricular injection of 0.6 µg SAP (lesion) or PBS (sham). Two months following surgery, APP/PS1 mice treated with SAP were significantly impaired compared to sham treated...... APP/PS1 mice in a behavioural paradigm addressing working memory. Conversely, the performance of Wt mice was unaffected by SAP treatment. Choline acetyltransferase activity was reduced in the hippocampus and frontal cortex following SAP treatment. The selective effect of a mild SAP lesion in APP/PS1...

  15. Applicability assessment of central and solar hot water systems integration in Serbia

    Directory of Open Access Journals (Sweden)

    Kljajić Miroslav V.

    2012-01-01

    Full Text Available Energy systems for consumers’ supply with sanitary hot water (SHW can be considered as a separate category of the system with many similar functions, performances and integral elements. This similarity of energy systems for SHW supply and the way in which they are used enable systemic planning, proposing and undertaking measures for improvements and advancements. This is possible not only by the reconstruction and modernization of existing technological solutions but also by their replacement with new, modern and more efficient solutions. The basic idea and the aim of this paper is the development of a concept for integrated and upgraded system of SHW supply for different types of buildings from residential to more complex buildings intended for different purposes. The analysis is based on the application of a systemic approach adapted to the conditions in urban communities and includes only modern but commercial technologies. This paper presents the results of a net energy analysis of integrated central and solar hot water supply system and compares it with the conventional sanitary hot water system in the City of Novi Sad, Serbia. The proposed methodology is demonstrated through a simulation example. It is shown that 23% reduction in the total system’s costs can be achieved as compared to the existing solution. Also, the methodology is applied to a residential block as a unit and obtained results indicate that investments in the development and construction of integrated systems are justified.

  16. Studies on the pharmacology of central cholinergic nerve terminals

    Energy Technology Data Exchange (ETDEWEB)

    Lapchak, P.A.

    1988-01-01

    The presynaptic regulation of acetylcholine (ACh) synthesis and release in the mammalian brain was studied. Vasoactive intestinal peptide (VIP) increased Ach synthesis by rat hippocampal slices; this effect was time-, concentration- and calcium-dependent. The VIP-induced increase in ACh synthesis was independent of either an alteration of high affinity choline uptake or altered ACh release. Activation of presynaptic opiate receptors by selective opiate agonists causes a concentration-dependent inhibition of potassium-evoked Ach release from rat and guinea-pig hippocampus, striatum and cerebral cortex; spontaneous ACh release was not affected by any opiate drug tested. ({sup 3}H)N-Methylcarbamylcholine (MCC) binds specifically to nicotinic binding sites in the rat brain; activation of nicotinic receptors in the rat hippocampus and frontal cortex by MCC or nicotine causes a dose-dependent facilitation of spontaneous ACh release. Chronic administration of nicotine to rats results in the upregulation of ({sup 3}H)MCC/nicotinic binding sites in certain regions of the rat brain; associated with the upregulation of the density of nicotinic sites was a concomitant down-regulation of functional nicotinic autoreceptors. This latter effect was reversible upon removal of nicotine, however, the time course of recovery of nicotinic auto-receptor function appears to be different from that of alterations of ({sup 3}H)MCC binding site number.

  17. Cholinergic pesticides cause mushroom body neuronal inactivation in honeybees

    OpenAIRE

    Palmer, Mary J; Moffat, Christopher; Saranzewa, Nastja; Harvey, Jenni; Wright, Geraldine A.; Connolly, Christopher N.

    2013-01-01

    Pesticides that target cholinergic neurotransmission are highly effective, but their use has been implicated in insect pollinator population decline. Honeybees are exposed to two widely used classes of cholinergic pesticide: neonicotinoids (nicotinic receptor agonists) and organophosphate miticides (acetylcholinesterase inhibitors). Although sublethal levels of neonicotinoids are known to disrupt honeybee learning and behaviour, the neurophysiological basis of these effects has not been shown...

  18. Cholinergic Mechanisms in the Cerebral Cortex: Beyond Synaptic Transmission.

    Science.gov (United States)

    Ovsepian, Saak V; O'Leary, Valerie B; Zaborszky, Laszlo

    2016-06-01

    Functional overviews of cholinergic mechanisms in the cerebral cortex have traditionally focused on the release of acetylcholine with modulator and transmitter effects. Recently, however, data have emerged that extend the role of acetylcholine and cholinergic innervations to a range of housekeeping and metabolic functions. These include regulation of amyloid precursor protein (APP) processing with production of amyloid β (Aβ) and other APP fragments and control of the phosphorylation of microtubule-associated protein (MAP) tau. Evidence has been also presented for receptor-ligand like interactions of cholinergic receptors with soluble Aβ peptide and MAP tau, with modulator and signaling effects. Moreover, high-affinity binding of Aβ to the neurotrophin receptor p75 (p75NTR) enriched in basalo-cortical cholinergic projections has been implicated in clearance of Aβ and nucleation of amyloid plaques. Here, we critically evaluate these unorthodox cholinergic mechanisms and discuss their role in neuronal physiology and the biology of Alzheimer's disease. PMID:26002948

  19. The basal forebrain cholinergic system in aging and dementia : Rescuing cholinergic neurons from neurotoxic amyloid-beta 42 with memantine

    NARCIS (Netherlands)

    Nyakas, Csaba; Granic, Ivica; Halmy, Laszlo G.; Banerjee, Pradeep; Luiten, Paul G. M.

    2011-01-01

    The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in the pathogenesis of Alzheimer's disease (AD). The evidence pointing to cholinergic impairments come from studies that report a decline in the activity of choli

  20. Effects of pro-cholinergic treatment in patients suffering from spatial neglect

    Directory of Open Access Journals (Sweden)

    Nadia eLucas

    2013-09-01

    Full Text Available Spatial neglect is a neurological condition characterized by a breakdown of spatial cognition contralateral to hemispheric damage. Deficits in spatial attention towards the contralesional side are considered to be central to this syndrome. Brain lesions typically involve right fronto-parietal cortices mediating attentional functions and subcortical connections in underlying white matter. Convergent findings from neuroimaging and behavioral studies in both animals and humans suggest that the cholinergic system might also be critically implicated in selective attention by modulating cortical function via widespread projections from the basal forebrain. Here we asked whether deficits in spatial attention associated with neglect could partly result from a cholinergic deafferentation of cortical areas subserving attentional functions, and whether such disturbances could be alleviated by pro-cholinergic therapy. We examined the effect of a single-dose transdermal nicotine treatment on spatial neglect in 10 stroke patients in a double-blind placebo-controlled protocol, using a standardized battery of neglect tests. Nicotine induced systematic improvement on cancellation tasks and facilitated orienting to single visual targets, but had no significant effect on other tests. These results support a global effect of nicotine on attention and arousal, but no effect on other spatial mechanisms impaired in neglect.

  1. ROLE OF CHOLINERGIC SYSTEM ON THE CONSTRUCTION OF MEMORY AND ITS INTERACTION WITH DOPAMINERGIC SYSTEM

    Directory of Open Access Journals (Sweden)

    F. Z. Zangeneh

    2006-07-01

    Full Text Available The central cholinergic system has been associated with cognitive function and memory and acetylcholine plays an important role during the early stages of memory consolidation. In this study, after training mice were tested with one way active avoidance procedure and retention were tested at 4, 8, 12, 16 and 24 hours of training and compared with non-shocked mice, in which it took 24 hours, a suitable time for retention test. Low dose administration of arecoline and physostigmine pre-training, immediate post-training and before retrieval showed that muscarinic agonist arecoline can potentiated memory in post trained and retrieval phases and reversible cholinesterase inhibitor physostigmine potentiated memory only in retrieval phase. Scopolamine disrupted acetylcholine potentiation only in retrieval phase. In the second part of this study, the effect of dopaminergic system was investigated. Low dose of apomorphine and D2 agonist bromocriptine potentiated memory when administered immediately post-training, and D2 antagonist sulpiride impaired memory. When the cholinergic system was blocked by scopolamine immediately post-training, apomorphine and bromocriptine potentiated memory and sulpiride impaired it. In conclusion, these results suggest that, cholinergic system in retrieval phase is very critical and there was no interaction between the two systems in the post-training phase.

  2. Pharmacological identification of cholinergic receptor subtypes on Drosophila melanogaster larval heart.

    Science.gov (United States)

    Malloy, Cole A; Ritter, Kyle; Robinson, Jonathan; English, Connor; Cooper, Robin L

    2016-01-01

    The Drosophila melanogaster heart is a popular model in which to study cardiac physiology and development. Progress has been made in understanding the role of endogenous compounds in regulating cardiac function in this model. It is well characterized that common neurotransmitters act on many peripheral and non-neuronal tissues as they flow through the hemolymph of insects. Many of these neuromodulators, including acetylcholine (ACh), have been shown to act directly on the D. melanogaster larval heart. ACh is a primary neurotransmitter in the central nervous system (CNS) of vertebrates and at the neuromuscular junctions on skeletal and cardiac tissue. In insects, ACh is the primary excitatory neurotransmitter of sensory neurons and is also prominent in the CNS. A full understanding regarding the regulation of the Drosophila cardiac physiology by the cholinergic system remains poorly understood. Here we use semi-intact D. melanogaster larvae to study the pharmacological profile of cholinergic receptor subtypes, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs), in modulating heart rate (HR). Cholinergic receptor agonists, nicotine and muscarine both increase HR, while nAChR agonist clothianidin exhibits no significant effect when exposed to an open preparation at concentrations as low as 100 nM. In addition, both nAChR and mAChR antagonists increase HR as well but also display capabilities of blocking agonist actions. These results provide evidence that both of these receptor subtypes display functional significance in regulating the larval heart's pacemaker activity.

  3. Chronic administration of sulbutiamine improves long term memory formation in mice: possible cholinergic mediation.

    Science.gov (United States)

    Micheau, J; Durkin, T P; Destrade, C; Rolland, Y; Jaffard, R

    1985-08-01

    Thiamine deficiency in both man and animals is known to produce memory dysfunction and cognitive disorders which have been related to an impairment of cholinergic activity. The present experiment was aimed at testing whether, inversely, chronic administration of large doses of sulbutiamine would have a facilitative effect on memory and would induce changes in central cholinergic activity. Accordingly mice received 300 mg/kg of sulbutiamine daily for 10 days. They were then submitted to an appetitive operant level press conditioning test. When compared to control subjects, sulbutiamine treated mice learned the task at the same rate in a single session but showed greatly improved performance when tested 24 hr after partial acquisition of the same task. Parallel neurochemical investigations showed that the treatment induced a slight (+ 10%) but significant increase in hippocampal sodium-dependent high affinity choline uptake. The present findings and previous results suggest that sulbutiamine improves memory formation and that this behavioral effect could be mediated by an increase in hippocampal cholinergic activity. PMID:4059305

  4. BLOCKADE OF CENTRAL NICOTINE ACETYLCHOLINE RECEPTOR SIGNALING ATTENUATE GHRELIN-INDUCED FOOD INTAKE IN RODENTS

    OpenAIRE

    S.L. Dickson; Hrabovszky, E; Hansson, C.; Jerlhag, E.; Alvarez-Crespo, M.; Skibicka, K. P.; Molnar, C. S.; Liposits, Z; Engel, J. A.; Egecioglu, E.

    2010-01-01

    Here we sought to determine whether ghrelin's central effects on food intake can be interrupted by nicotinic cholinergic receptor (nAChR) blockade. Ghrelin regulates mesolimbic dopamine neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc), partly via cholinergic VTA afferents originating in the laterodorsal tegmental area (LDTg). Given that these cholinergic projections to the VTA have been implicated in natural as well as drug-induced reinforcement, we sou...

  5. Affects as central organising and integrating factors. A new psychosocial/biological model of the psyche.

    Science.gov (United States)

    Ciompi, L

    1991-07-01

    A new psychosocial/biological model of the psyche is proposed, in which the affects play a central role in organising and integrating cognition. The psyche is understood here as a complex hierarchical structure of affective/cognitive systems of reference (or 'programmes for feeling, thinking, and behaviour'), generated by repetitive concrete action. These systems store past experience in their structure, and provide the functional basis for further cognition and communication. Affects endow these programmes with a specific qualitative value (such as motivation), connect cognitive elements synchronically and diachronically, and contribute to their storage and mobilisation according to context. They also participate in differentiating cognitive systems at higher levels of abstraction. These assumptions are supported by recent findings on the role of the limbic and hypothalamic system for the regulation of emotion, on neuronal plasticity, and on the phenomenon of state-dependent learning and memory. Refutable hypotheses are formulated for further research on the interaction of emotion and cognition.

  6. Integrated approach for understanding spatio-temporal changes in forest resource distribution in the central Himalaya

    Institute of Scientific and Technical Information of China (English)

    A K Joshi; P K Joshi; T Chauhan; Brijmohan Bairwa

    2014-01-01

    Intense anthropogenic exploitation has altered distribution of forest resources. This change was analyzed using visual interpretation of satellite data of 1979, 1999 and 2009. Field and interactive social surveys were conducted to identify spatial trends in forest degradation and data were mapped on forest cover and land use maps. Perceptions of villagers were compiled in a pictorial representation to understand changes in forest resource distribution in central Himalaya from 1970 to 2010. For-ested areas were subject to degradation and isolation due to loss of con-necting forest stands. Species like Lantana camara and Eupatorium adenophorum invaded forest landscapes. Intensity of human pressure differed by forest type and elevation. An integrated approach is needed to monitor forest resource distribution and disturbance.

  7. Integration of a central protein repository into a standard data processing application for mining proteomics data

    DEFF Research Database (Denmark)

    Fritzemeier, Kai; Kristensen, Jakob; Larsen, Martin Røssel;

    efficient data mining and categorizing of large data sets. Methods All samples were analyzed on an Orbitrap mass Spectrometer coupled to a nano Easy LC. The proteomics repository database is built using the Sun Java technology and the Microsoft mySQL database technology for optimal performance. Proteome......Novel Aspect All major protein repositories integrated into a central domain for direct analyses and interpretation in a standard proteomics data analysis software. Introduction Modern proteomics must face the challenge of performing bioinformatics analysis and comparison of large datasets....... It is a time consuming and at times nearly impossible task to distinguish known proteins from novel proteins in these data sets without proper annotation and comparison with literature sources. Tools are needed that can handle the complexity of these data including: redundancy (same protein but different...

  8. Integration of decentralized torrefaction with centralized catalytic pyrolysis to produce green aromatics from coffee grounds.

    Science.gov (United States)

    Chai, Li; Saffron, Christopher M; Yang, Yi; Zhang, Zhongyu; Munro, Robert W; Kriegel, Robert M

    2016-02-01

    The aim of this work was to integrate decentralized torrefaction with centralized catalytic pyrolysis to convert coffee grounds into the green aromatic precursors of terephthalic acid, namely benzene, toluene, ethylbenzene, and xylenes (BTEX). An economic analysis of this bioproduct system was conducted to examine BTEX yields, biomass costs and their sensitivities. Model predictions were verified experimentally using pyrolysis GC/MS to quantify BTEX yields for raw and torrefied biomass. The production cost was minimized when the torrefier temperature and residence time were 239°C and 34min, respectively. This optimization study found conditions that justify torrefaction as a pretreatment for making BTEX, provided that starting feedstock costs are below $58 per tonne. PMID:26684175

  9. Integration of decentralized torrefaction with centralized catalytic pyrolysis to produce green aromatics from coffee grounds.

    Science.gov (United States)

    Chai, Li; Saffron, Christopher M; Yang, Yi; Zhang, Zhongyu; Munro, Robert W; Kriegel, Robert M

    2016-02-01

    The aim of this work was to integrate decentralized torrefaction with centralized catalytic pyrolysis to convert coffee grounds into the green aromatic precursors of terephthalic acid, namely benzene, toluene, ethylbenzene, and xylenes (BTEX). An economic analysis of this bioproduct system was conducted to examine BTEX yields, biomass costs and their sensitivities. Model predictions were verified experimentally using pyrolysis GC/MS to quantify BTEX yields for raw and torrefied biomass. The production cost was minimized when the torrefier temperature and residence time were 239°C and 34min, respectively. This optimization study found conditions that justify torrefaction as a pretreatment for making BTEX, provided that starting feedstock costs are below $58 per tonne.

  10. Comparison of GNSS integrated water vapor and NWM reanalysis data over Central and South America

    Science.gov (United States)

    Fernández, Laura Isabel; Natali, Maria Paula; Meza, Amalia; Mendoza, Luciano; Bianchi, Clara

    2016-07-01

    Integrated water vapor (IWV) derived from Global Navigation Satellite Systems (GNSS) and Numerical Weather Models (NWM) reanalysis data were compared in order to assess the consistency between the different datasets over the extended geographical region of Central and South America. The analysis was performed for the seven years period between 2007 and 2013. We analyzed two different NWM: the European Centre for Medium-Range Weather Forecast (ECMWF) reanalysis data (ERA Interim) and the Modern-Era Retrospective analysis for Research and Applications (MERRA) from the National Aeronautics and Space Administration (NASA). The statistical analysis of the differences was performed in 110 GNSS sites (GPS + GLONASS), although the most interesting results came from the 73 sites which have more than 5 years of data. The selected area involves different climate types, from polar to tropical, and it is characterized by large temporal variability of the integrated total humidity content. Moreover, the scarce coverage of operational radio sounding stations is noticeable in large areas of the selected region; hence the contribution of IWV-GNSS is essential to improve the weather understanding. Considering that the atmospheric water vapor has a highly variable and complex distribution which knowledge is essential for weather prediction and local meteorological studies. This study aims to provide IWV-GNSS observations able to be assimilated by operational weather centers, for both prediction and simulation, as well for improving regional modeling.

  11. GABAergic actions on cholinergic laterodorsal tegmental neurons

    DEFF Research Database (Denmark)

    Kohlmeier, K A; Kristiansen, Uffe

    2010-01-01

    Cholinergic neurons of the pontine laterodorsal tegmentum (LDT) play a critical role in regulation of behavioral state. Therefore, elucidation of mechanisms that control their activity is vital for understanding of how switching between wakefulness, sleep and anesthetic states is effectuated....... In vivo studies suggest that GABAergic mechanisms within the pons play a critical role in behavioral state switching. However, the postsynaptic, electrophysiological actions of GABA on LDT neurons, as well as the identity of GABA receptors present in the LDT mediating these actions is virtually unexplored...... neurons. Post-synaptic location of GABA(A) receptors was demonstrated by persistence of muscimol-induced inward currents in TTX and low Ca(2+) solutions. THIP, a selective GABA(A) receptor agonist with a preference for d-subunit containing GABA(A) receptors, induced inward currents, suggesting...

  12. Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats

    DEFF Research Database (Denmark)

    Abelson, Klas S P; Kommalage, Mahinda; Höglund, A Urban

    2004-01-01

    Aspirin and paracetamol have been shown to suppress non-inflammatory pain conditions like thermal, visceral and mechanical pain in mice and rats. The non-inflammatory antinociception appears to be mediated by central receptor mechanisms, such as the cholinergic system. In this study, we tested...... the hypothesis that the non-inflammatory antinociception of aspirin and paracetamol could be mediated by an increase of intraspinal acetylcholine release. Microdialysis probes were placed intraspinally in anesthetized rats for acetylcholine sampling. Subcutaneously administered aspirin 100 and 300 mg...

  13. Suppression of glucocorticoid secretion enhances cholinergic transmission in rat hippocampus.

    Science.gov (United States)

    Mizoguchi, Kazushige; Shoji, Hirotaka; Ikeda, Ryuji; Tanaka, Yayoi; Maruyama, Wakako; Tabira, Takeshi

    2008-08-15

    We previously demonstrated that suppression of glucocorticoid secretion by adrenalectomy (ADX) impaired prefrontal cortex-sensitive working memory, but not reference memory. Since the cholinergic system in the hippocampus is also involved in these memories, we examined the effects of glucocorticoid suppression on cholinergic transmission in the rat hippocampus. A microdialysis study revealed that ADX did not affect the basal acetylcholine release, but enhanced the KCl-evoked response. This enhanced response was reversed by the corticosterone replacement treatment. The extracellular choline concentrations increased under both basal and KCl-stimulated conditions in the ADX rats, and these increases were also reversed by the corticosterone replacement. These results indicate that suppression of glucocorticoid secretion enhances cholinergic transmission in the hippocampus in response to stimuli. It is possible that this enhanced cholinergic transmission may not contribute to the ADX-induced working memory impairment, but it may be involved in maintenance of reference memory.

  14. Striatal cholinergic interneurons Drive GABA release from dopamine terminals.

    Science.gov (United States)

    Nelson, Alexandra B; Hammack, Nora; Yang, Cindy F; Shah, Nirao M; Seal, Rebecca P; Kreitzer, Anatol C

    2014-04-01

    Striatal cholinergic interneurons are implicated in motor control, associative plasticity, and reward-dependent learning. Synchronous activation of cholinergic interneurons triggers large inhibitory synaptic currents in dorsal striatal projection neurons, providing one potential substrate for control of striatal output, but the mechanism for these GABAergic currents is not fully understood. Using optogenetics and whole-cell recordings in brain slices, we find that a large component of these inhibitory responses derive from action-potential-independent disynaptic neurotransmission mediated by nicotinic receptors. Cholinergically driven IPSCs were not affected by ablation of striatal fast-spiking interneurons but were greatly reduced after acute treatment with vesicular monoamine transport inhibitors or selective destruction of dopamine terminals with 6-hydroxydopamine, indicating that GABA release originated from dopamine terminals. These results delineate a mechanism in which striatal cholinergic interneurons can co-opt dopamine terminals to drive GABA release and rapidly inhibit striatal output neurons.

  15. Integration of vision and central pattern generator based locomotion for path planning of a non-holonomic crawling humanoid robot

    OpenAIRE

    Gay, Sébastien; Dégallier Rochat, Sarah; Ijspeert, Auke; Santos-Victor, José

    2010-01-01

    In this paper we present our work on integrating a locomotion controller based on central pattern generator (CPG) and a motion planning algorithm using artificial potential fields for a non-holonomic crawling humanoid robot, the iCub. We also integrated a vision tracker and an inverse kinematics solver to perform reaching tasks. We study the influence of the various parameters of the potential field equations on the performance of the system and prove the efficiency of our framework by testin...

  16. Cholinergic Mechanisms in Spinal Locomotion - Potential Target for Rehabilitation Approaches

    OpenAIRE

    Jordan, L M; Noga, B. R.; Cabaj, A. M.; J Provencher

    2014-01-01

    Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Test...

  17. Astrocytes mediate in vivo cholinergic-induced synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Marta Navarrete

    2012-02-01

    Full Text Available Long-term potentiation (LTP of synaptic transmission represents the cellular basis of learning and memory. Astrocytes have been shown to regulate synaptic transmission and plasticity. However, their involvement in specific physiological processes that induce LTP in vivo remains unknown. Here we show that in vivo cholinergic activity evoked by sensory stimulation or electrical stimulation of the septal nucleus increases Ca²⁺ in hippocampal astrocytes and induces LTP of CA3-CA1 synapses, which requires cholinergic muscarinic (mAChR and metabotropic glutamate receptor (mGluR activation. Stimulation of cholinergic pathways in hippocampal slices evokes astrocyte Ca²⁺ elevations, postsynaptic depolarizations of CA1 pyramidal neurons, and LTP of transmitter release at single CA3-CA1 synapses. Like in vivo, these effects are mediated by mAChRs, and this cholinergic-induced LTP (c-LTP also involves mGluR activation. Astrocyte Ca²⁺ elevations and LTP are absent in IP₃R2 knock-out mice. Downregulating astrocyte Ca²⁺ signal by loading astrocytes with BAPTA or GDPβS also prevents LTP, which is restored by simultaneous astrocyte Ca²⁺ uncaging and postsynaptic depolarization. Therefore, cholinergic-induced LTP requires astrocyte Ca²⁺ elevations, which stimulate astrocyte glutamate release that activates mGluRs. The cholinergic-induced LTP results from the temporal coincidence of the postsynaptic activity and the astrocyte Ca²⁺ signal simultaneously evoked by cholinergic activity. Therefore, the astrocyte Ca²⁺ signal is necessary for cholinergic-induced synaptic plasticity, indicating that astrocytes are directly involved in brain storage information.

  18. Assimilation or integration: Similarities and differences between acculturation attitudes of migrants from Central Asia and Russians in Central Russia.

    OpenAIRE

    Lebedeva N. M.

    2016-01-01

    This paper is dedicated to the cultural specificities of three typical collective groups with respect to the representation of love. The research subject focuses on the cross-cultural similarities and differences in how love is conceptualized among highly educated citizens of Brazil (50), Russia (50), and Central Africa (50) (age range 21–60; M = 34). We used “The Classical ideas of love: acceptance and distancing” questionnaire (I.A. Djidaryan, E.V. Belovol, & O.V. Maslova) and the “Directed...

  19. Amyloid-β depresses excitatory cholinergic synaptic transmission in Drosophila

    Institute of Scientific and Technical Information of China (English)

    Liqun Fang; Jingjing Duan; Dongzhi Ran; Zihao Fan; Ying Yan; Naya Huang; Huaiyu Gu; Yulan Zhu

    2012-01-01

    Objective Decline,disruption,or alterations of nicotinic cholinergic mechanisms contribute to cognitive dysfunctions like Alzheimer's disease (AD).Although amyloid-β (Aβ) aggregation is a pathological hallmark of AD,the mechanisms by which Aβ peptides modulate cholinergic synaptic transmission and memory loss remain obscure.This study was aimed to investigate the potential synaptic modulation by Aβ of the cholinergic synapses between olfactory receptor neurons and projection neurons (PNs) in the olfactory lobe of the fruit fly.Methods Cholinergic spontaneous and miniature excitatory postsynaptic current (mEPSC) were recorded with whole-cell patch clamp from PNs in Drosophila AD models expressing Aβ40,Aβ42,or Aβ42Arc peptides in neural tissue.Results In fly pupae (2 days before eclosion),overexpression of Aβ42 or Aβ42Arc,but not Aβ40,led to a significant decrease of mEPSC frequency,while overexpression of Aβ40,Aβ42,or Aβ42Arc had no significant effect on mEPSC amplitude.In contrast,Pavlovian olfactory associative learning and lifespan assays showed that both short-term memory and lifespan were decreased in the Drosophila models expressing Aβ40,Aβ42,or Aβ42Arc.Conclusion Both electrophysiological and behavioral results showed an effect of Aβ peptide on cholinergic synaptic transmission and suggest a possible mechanism by which Aβ peptides cause cholinergic neuron degeneration and the consequent memory loss.

  20. Experimental investigation of integrated air purifying technology for bioaerosol removal and inactivation in central air-conditioning system

    Institute of Scientific and Technical Information of China (English)

    ZHENG Xiaohong; LIU Hongmin; YE Xiaojiang; LI Kejun; WANG Ruzhu; ZHAO Liping; Lisa. X. Xu; CHEN Yazhu; JIN Xinqiao; GU Bo; BAI Jingfeng

    2004-01-01

    In this research, high voltage static electricity and ultraviolet technologies were integrated to an air purifying device which can be used to trap and kill airborne bacteria and viruses in central air-conditioning systems. An experimental platform was built to mimic the central air system, in which the efficacy of the newly built device was examined. In addition to the standard physical and chemical tests, bacteriophages were used to simulate airborne viruses in the experimental system. The bacteriophage suspension was aerosolized into the air with ultrasonic wave atomization. The result showed that more than 86% removal efficiency of micro-particles (<10 micron in diameter) were removed after the device was in operation in a building and more than 95% of bacteriophages in the experimental system. It is concluded that the integrated air purifier is suitable for controlling air quality and preventing virus transmission through the central air system.

  1. Cytochemical demonstration of cholinergic, serotoninergic and peptidergic nerve elements in Gorgoderina vitelliloba (Trematoda: Digenea).

    Science.gov (United States)

    McKay, D M; Halton, D W; Johnston, C F; Fairweather, I; Shaw, C

    1991-02-01

    Standard enzyme cytochemical and indirect immunocytochemical techniques have been used in conjunction with light and confocal scanning laser microscopy (CSLM) to visualize cholinergic, serotoninergic and peptidergic nerve elements in whole-mount preparations of the amphibian urinary-bladder fluke, Gorgoderina vitelliloba. Cholinesterase (ChE) activity was localized in paired anterior ganglia, a connecting dorsal commissure and in the origins of the ventral nerve cords. Cholinergic ganglia were also evident in shelled embryos in the uterus. Serotonin-immunoreactivity (IR) was more extensive than ChE activity and was identified in both the central and peripheral nervous systems. Serotoninergic nerve fibres were associated with the somatic musculature and female reproductive ducts. Antisera to nine mammalian peptides and one invertebrate (FMRFamide) peptide have been used to investigate the peptidergic nervous system in the parasite. Immunoreactivity was obtained to five peptides, namely pancreatic polypeptide (PP), peptide YY (PYY), neuropeptide Y (NPY), substance P (SP) and FMRFamide. Peptidergic nerve fibres were found to be more abundant than demonstrable cholinergic or serotoninergic nerve fibres. NPY-IR was identified only in the main components of the central nervous system. However, PP- and PYY-IR occurred in the anterior ganglia, dorsal commissure, main nerve cords and in numerous small varicose fibres that ramified throughout the worm. Additionally, PP-immunoreactive nerve fibres were found to innervate the musculature of the female reproductive tracts. Six sites of IR were found in the acetabulum, using antisera directed towards the C-terminal end of PP and PYY, and these matched with the distribution of six non-ciliated rosette-like papillae observed by scanning electron microscopy. SP- and FMRFamide-IR were identified in the CNS, and FMRFamide-immunopositive nerve fibres were also evident in association with the gonopore cirrus region and with the

  2. Monitoring cholinergic activity during attentional performance in mice heterozygous for the choline transporter: a model of cholinergic capacity limits.

    Science.gov (United States)

    Paolone, Giovanna; Mallory, Caitlin S; Koshy Cherian, Ajeesh; Miller, Thomas R; Blakely, Randy D; Sarter, Martin

    2013-12-01

    Reductions in the capacity of the human choline transporter (SLC5A7, CHT) have been hypothesized to diminish cortical cholinergic neurotransmission, leading to risk for cognitive and mood disorders. To determine the acetylcholine (ACh) release capacity of cortical cholinergic projections in a mouse model of cholinergic hypofunction, the CHT+/- mouse, we assessed extracellular ACh levels while mice performed an operant sustained attention task (SAT). We found that whereas SAT-performance-associated increases in extracellular ACh levels of CHT+/- mice were significantly attenuated relative to wildtype littermates, performance on the SAT was normal. Tetrodotoxin-induced blockade of neuronal excitability reduced both dialysate ACh levels and SAT performance similarly in both genotypes. Likewise, lesions of cholinergic neurons abolished SAT performance in both genotypes. However, cholinergic activation remained more vulnerable to the reverse-dialyzed muscarinic antagonist atropine in CHT+/- mice. Additionally, CHT+/- mice displayed greater SAT-disrupting effects of reverse dialysis of the nAChR antagonist mecamylamine. Receptor binding assays revealed a higher density of α4β2* nAChRs in the cortex of CHT+/- mice compared to controls. These findings reveal compensatory mechanisms that, in the context of moderate cognitive challenges, can overcome the performance deficits expected from the significantly reduced ACh capacity of CHT+/- cholinergic terminals. Further analyses of molecular and functional compensations in the CHT+/- model may provide insights into both risk and resiliency factors involved in cognitive and mood disorders.

  3. Intrinsic cholinergic neurons in the hippocampus: fact or artefact?

    Directory of Open Access Journals (Sweden)

    Jan Krzysztof Blusztajn

    2016-03-01

    Full Text Available It is generally agreed that hippocampal acetylcholine (ACh is synthesized and released exclusively from the terminals of the long-axon afferents whose cell bodies reside in the medial septum and diagonal band. The search for intrinsic cholinergic neurons in the hippocampus has a long history; however evidence for the existence of these neurons has been inconsistent, with most investigators failing to detect them using in situ hybridization or immunohistochemical staining of the cholinergic markers, choline acetyltransferase (CHAT or vesicular acetylcholine transporter (VACHT. Advances in the use of bacterial artificial chromosome (BAC transgenic mice expressing a reporter protein under the control of the genomic elements of the Chat gene (Chat-BAC mice have facilitated studies of cholinergic neurons. Such mice show robust and faithful expression of the reporter proteins in all known cholinergic cell populations. The availability of the Chat-BAC mice re-ignited interest in hippocampal cholinergic interneurons, because a small number of such reporter-expressing cells is frequently observed in the hippocampus of these mice. However, to date, attempts to confirm that these neurons co-express the endogenous cholinergic markers CHAT or VACHT, or release ACh, have been unsuccessful. Without such confirmatory evidence it is best to conclude that there are no cholinergic neurons in the hippocampus. Similar considerations apply to other BAC transgenic lines, whose utility as a discovery tool for cell populations heretofore not known to express the genes of interest encoded by the BACs, must be validated by methods that detect expression of the endogenous genes.

  4. Effects of sustained proNGF blockade on attentional capacities in aged rats with compromised cholinergic system.

    Science.gov (United States)

    Yegla, B; Parikh, V

    2014-03-01

    Disruption in nerve growth factor (NGF) signaling via tropomyosin-related kinase A (trkA) receptors compromises the integrity of the basal forebrain (BF) cholinergic system, yielding cognitive, specifically attentional, impairments in Alzheimer's disease (AD). Although normal aging is considered a risk factor for AD, the mechanisms underlying the selective vulnerability of the aging cholinergic system to trkA disruption is not clear. The levels of proNGF, a proneurotrophin that possesses higher affinity for p75 receptors, increase in aging. The present study was designed to test the hypothesis that cholinergic and attentional dysfunction in aged rats with reduced BF trkA receptors occurs due to the overactivation of endogenous proNGF signaling. We employed a viral vector that produced trkA shRNA to suppress trkA receptors in the corticopetal cholinergic neurons of aged rats. BF trkA suppression impaired animals' performance on signal trials in both the sustained attention task (SAT) and the cognitively taxing distractor version of SAT (dSAT) and these deficits were normalized by chronic intracerebroventricular administration of proNGF antibody. Moreover, depolarization-evoked acetylcholine (ACh) release and the density of cortical cholinergic fibers were partially restored in these animals. However, SAT/dSAT scores reflecting overall performance did not improve following proNGF blockade in trkA knockdown rats due to impaired performance in non-signal trials. Sustained proNGF blockade alone did not alter baseline attentional performance but produced moderate impairments during challenging conditions. Collectively, our findings indicate that barring proNGF-p75 signaling may exert some beneficial effects on attentional capacities specifically when BF trkA signaling is abrogated. However, endogenous proNGF may also possess neurotrophic effects and blockade of this proneurotrophin may not completely ameliorate attentional impairments in AD and potentially hinder

  5. Economic Rationales for Central Banking: Historical Evolution, Policy Space, Institutional Integrity, and Paradigm Challenges

    OpenAIRE

    Poomjai Nacaskul; Kritchaya Janjaroen; Suparit Suwanik

    2012-01-01

    The late-2000s global financial crisis saw increased public profiles and balance sheets of both the US and European central banks, their combined series of financial rescue measures in effect pushing the envelope of central banking modus operandi. And in general, somewhat anecdotally amongst non-crisis Asia-Pacific/emerging economies, central banks are under increased pressure to pursue growth agenda, or at least being publicly called to task as to whether strict inflation regime is all that ...

  6. Cholinergic and adrenergic influence on the teleost heart in vivo.

    Science.gov (United States)

    Axelsson, M; Ehrenström, F; Nilsson, S

    1987-01-01

    The tonical cholinergic and adrenergic influence on the heart rate was investigated in vivo in seven species of marine teleosts (pollack, Pollachius pollachius; cuckoo wrasse, Labrus mixtus; ballan wrasse, Labrus berggylta; five-bearded rockling, Ciliata mustela; tadpole fish, Raniceps raninus; eel-pout, Zoarces viviparus and short-spined sea scorpion, Myoxocephalus scor pius) during rest and, in two of the species (P. pollachius and L. mixtus), also during moderate swimming exercise in a Blazka-type swim tunnel. Ventral aortic blood pressure and heart rate were recorded via a catheter implanted in an afferent branchial artery, and the influence of the cholinergic and adrenergic tonus on the heart rate was assessed by injection of atropine and sotalol respectively. During rest the adrenergic tonus was higher than the cholinergic tonus in all species except L. berggylta, where the reverse was true. In P. pollachius and L. mixtus, exercise appeared to produce a lowering of the cholinergic tonus on the heart and, possibly, a slight increase of the adrenergic tonus. The nature of the adrenergic tonus (humoral or neural) is not clear, but the low plasma concentrations of catecholamines both during rest and exercise could be interpreted in favour of a mainly neural adrenergic tonus on the teleost heart. These experiments are compatible with the view that both a cholinergic inhibitory tonus and an adrenergic excitatory tonus are general features in the control of the teleost heart in vivo, both at rest and during moderate swimming exercise.

  7. The Intelligence Promotion Effect and the Influence on Central Cholinergic Neuronal Function of Jieduyizhi Capsules%解毒益智胶囊的益智效应及对中枢胆碱能神经功能的影响

    Institute of Scientific and Technical Information of China (English)

    徐世军; 张文生; 赵宜军; 王永炎

    2011-01-01

    目的 观察解毒益智胶囊的益智效应及对中枢胆碱能神经功能的影响,为治疗轻度认知障碍提供实验依据.方法 建立东莨菪碱致小鼠学习记忆障碍模型.按体重随机分为正常对照组、模型对照组、安理申对照组及解毒益智胶囊高、中、低、极低剂量组.采用避暗法、跳台法和Morris水迷宫法观察解毒益智胶囊的益智效应;采用乙酰胆碱酯酶(AchE)试剂盒检测全脑AchE活性;采用实时荧光定量PCR技术,以18S rRNA为内参基因,用SYBR Green 1染料法检测海马M1受体和胆碱乙酞转移酶(ChAT)基因相对表达,双标准曲线法进行计算和数据分析.结果 解毒益智胶囊能显著延长东莨菪碱致模型小鼠学习记忆障碍模型避暗实验和跳台实验逃避潜伏期,减少错误次数,显著缩短Morris水迷宫实验平均逃避潜伏期,改善空间搜索策略;能显著提高学习记忆障碍小鼠模型全脑AchE的活性:显著增强海马M1受体和ChAT基因表达,解毒益智胶囊高、中、低、极低剂量组M1受体基因分别较模型组表达增高了14、9、7、3、8、2、1.8倍,而ChAT基因则分别较模型对照组提高了6.6、26.5、1.2、6.1倍.结论 解毒益智胶囊具有良好的益智作用.%Objective To explore the intelligence promotion effect and the influence on central cholinergic neuronal function of Jieduyizhi (JDYZ) Capsule in order to provide experimental basis for its treatment on mild cognitive impairment (MCI).Method The mice model with learning and memory deficits induced by scopolamine was established.The step through test, step down test and the Morris water maze test were applied on mice to assay the intelligence promotion effect of JDYZ Capsule.The AchE activity in the whole mice brain was tested by AchE kits.The relative gene expression of ChAT and M1 receptor in the hippocampus was tested by FQ-PCR (Time Fluorescent Quantitative PCR) and SYBR Green Ⅰ method, with the 18sRNA as a

  8. Evaluation of Integrated Community Case Management in Eight Districts of Central Uganda

    Science.gov (United States)

    Mubiru, Denis; Byabasheija, Robert; Bwanika, John Baptist; Meier, Joslyn Edelstein; Magumba, Godfrey; Kaggwa, Flavia Mpanga; Abusu, Jackson Ojera; Opio, Alex Chono; Lodda, Charles Clarke; Patel, Jaanki; Diaz, Theresa

    2015-01-01

    Objective Evidence is limited on whether Integrated Community Case Management (iCCM) improves treatment coverage of the top causes of childhood mortality (acute respiratory illnesses (ARI), diarrhoea and malaria). The coverage impact of iCCM in Central Uganda was evaluated. Methods Between July 2010 and December 2012 a pre-post quasi-experimental study in eight districts with iCCM was conducted; 3 districts without iCCM served as controls. A two-stage household cluster survey at baseline (n = 1036 and 1042) and end line (n = 3890 and 3844) was done in the intervention and comparison groups respectively. Changes in treatment coverage and timeliness were assessed using difference in differences analysis (DID). Mortality impact was modelled using the Lives Saved Tool. Findings 5,586 Village Health Team members delivered 1,907,746 treatments to children under age five. Use of oral rehydration solution (ORS) and zinc treatment of diarrhoea increased in the intervention area, while there was a decrease in the comparison area (DID = 22.9, p = 0.001). Due to national stock-outs of amoxicillin, there was a decrease in antibiotic treatment for ARI in both areas; however, the decrease was significantly greater in the comparison area (DID = 5.18; p<0.001). There was a greater increase in Artemisinin Combination Therapy treatment for fever in the intervention areas than in the comparison area but this was not significant (DID = 1.57, p = 0.105). In the intervention area, timeliness of treatments for fever and ARI increased significantly higher in the intervention area than in the comparison area (DID = 2.12, p = 0.029 and 7.95, p<0.001, respectively). An estimated 106 lives were saved in the intervention area while 611 lives were lost in the comparison area. Conclusion iCCM significantly increased treatment coverage for diarrhoea and fever, mitigated the effect of national stock outs of amoxicillin on ARI treatment, improved timeliness of treatments for fever and ARI and saved

  9. Evaluation of Integrated Community Case Management in Eight Districts of Central Uganda.

    Directory of Open Access Journals (Sweden)

    Denis Mubiru

    Full Text Available Evidence is limited on whether Integrated Community Case Management (iCCM improves treatment coverage of the top causes of childhood mortality (acute respiratory illnesses (ARI, diarrhoea and malaria. The coverage impact of iCCM in Central Uganda was evaluated.Between July 2010 and December 2012 a pre-post quasi-experimental study in eight districts with iCCM was conducted; 3 districts without iCCM served as controls. A two-stage household cluster survey at baseline (n = 1036 and 1042 and end line (n = 3890 and 3844 was done in the intervention and comparison groups respectively. Changes in treatment coverage and timeliness were assessed using difference in differences analysis (DID. Mortality impact was modelled using the Lives Saved Tool.5,586 Village Health Team members delivered 1,907,746 treatments to children under age five. Use of oral rehydration solution (ORS and zinc treatment of diarrhoea increased in the intervention area, while there was a decrease in the comparison area (DID = 22.9, p = 0.001. Due to national stock-outs of amoxicillin, there was a decrease in antibiotic treatment for ARI in both areas; however, the decrease was significantly greater in the comparison area (DID = 5.18; p<0.001. There was a greater increase in Artemisinin Combination Therapy treatment for fever in the intervention areas than in the comparison area but this was not significant (DID = 1.57, p = 0.105. In the intervention area, timeliness of treatments for fever and ARI increased significantly higher in the intervention area than in the comparison area (DID = 2.12, p = 0.029 and 7.95, p<0.001, respectively. An estimated 106 lives were saved in the intervention area while 611 lives were lost in the comparison area.iCCM significantly increased treatment coverage for diarrhoea and fever, mitigated the effect of national stock outs of amoxicillin on ARI treatment, improved timeliness of treatments for fever and ARI and saved lives.

  10. Prevalence of Chromosomally Integrated Human Herpesvirus 6 (HHV-6) in Patients with HHV-6 Central Nervous System Dysfunction

    OpenAIRE

    Hill, Joshua A; Sedlak, Ruth Hall; Zerr, Danielle M.; Huang, Meei-Li; Yeung, Cecilia; Myerson, David; Jerome, Keith R.; Boeckh, Michael J.

    2014-01-01

    We identified 37 hematopoietic cell transplantation recipients with human herpesvirus 6 (HHV-6) central nervous system dysfunction and tested donors/recipients for chromosomally integrated (ci)HHV-6. One patient had ciHHV-6A with possible HHV-6A reactivation and encephalitis. There was no ciHHV-6 enrichment in this group, but larger studies are needed to determine if patients with ciHHV-6 are at increased risk for HHV-6-associated diseases or other complications.

  11. Morphine dependence and withdrawal induced changes in cholinergic signaling

    Science.gov (United States)

    Neugebauer, Nichole M.; Einstein, Emily B.; Lopez, Maria B.; McClure-Begley, Tristan D.; Mineur, Yann S.; Picciotto, Marina R.

    2013-01-01

    Cholinergic signaling is thought to be involved in morphine dependence and withdrawal, but the specific mechanisms involved remain unclear. The current study aimed to identify alterations in the cholinergic system that may contribute to the development of morphine dependence and withdrawal. Acetylcholinesterase (AChE) activity and [3H]-epibatidine binding were evaluated in order to determine if morphine dependence and withdrawal induces alterations in cholinergic signaling or expression of high affinity nicotinic acetylcholine receptors (nAChRs) in the midbrain (MB), medial habenula (MHb) and interpeduncular nucleus (IPN). The effect of cholinergic signaling through nAChRs on morphine-withdrawal induced jumping behavior was then determined. Lastly, the contribution of β4-containing nAChRs receptors in the MHb to morphine-withdrawal induced jumping behavior and neuronal activity as indicated by c-fos expression was assessed. Chronic morphine administration decreased AChE activity in MB and MHb, an effect that was no longer present following precipitated withdrawal. Morphine dependent mice showed increased nicotinic acetylcholine receptor (nAChR) levels in MB. Further, nicotine (0.4 mg/kg) and lobeline (3 mg/kg) decreased jumping behavior while mecamylamine (1 mg/kg) had no effect. Knock-down of β4 subunit-containing nAChRs in the MHb attenuated c-fos activation, but did not decrease morphine withdrawal-induced jumping. Thus, morphine withdrawal induces cholinergic signaling in the MHb, but this does not appear to be responsible for the effects of cholinergic drugs on somatic signs of opiate withdrawal, as measured by jumping behavior. PMID:23651795

  12. The Integrated Soil Erosion Risk Management Model of Central Java, Indonesia

    Science.gov (United States)

    Setiawan, M. A.; Stoetter, J.; Sartohadi, J.; Christanto, N.

    2009-04-01

    tolerable soil erosion rate, the soil erosion management will be applied base on cost and benefit analysis. The soil erosion management measures will conduct as decision maker of defining the best alternative soil conservation method in a certain area. Besides the engineering and theoretical methods, the local wisdom also will be taken into account in defining the alternative manners of soil erosion management. As a prototype, this integrated model will be generated and simulated in Serayu Watershed, Central Java, since this area has a serious issue in soil erosion problem mainly in the upper stream area (Dieng area). The extraordinary monoculture plantation (potatoes) and very intensive soil tillage without proper soil conservation method has accelerated the soil erosion and depleted the soil fertility. Based on the potatoes productivity data (kg/ha) from 1997-2007 showed that there was a declining trend line, approximately minus 8,2% every year. On the other hand the fertilizer and pesticide consumption in agricultural land are significantly increasing every year. In the same time, the high erosion rate causes serious sedimentation problem in lower stream. Those conditions can be used as study case in determining the element at risk of soil erosion and calculation method for the total soil erosion cost (on-site and off-site effect). Moreover, The Serayu Watershed consists of complex landforms which might have variation of soil erosion tolerable rate. In the future, this integrated model can obtain valuable basis data of the soil erosion hazard in spatial and temporal information including its total cost, the sustainability time of certain land or agriculture area, also the consequences price of applying certain agriculture or soil management. Since this model give result explicitly in spatial and temporal, this model can be used by the local authority to run the land use scenario in term of soil erosion impact before applied them in the real condition. In practice, such

  13. Formal Pseudodifferential Operators in One and Several Variables, Central Extensions, and Integrable Systems

    Directory of Open Access Journals (Sweden)

    Jarnishs Beltran

    2015-01-01

    Full Text Available We review some aspects of the theory of Lie algebras of (twisted and untwisted formal pseudodifferential operators in one and several variables in a general algebraic context. We focus mainly on the construction and classification of nontrivial central extensions. As applications, we construct hierarchies of centrally extended Lie algebras of formal differential operators in one and several variables, Manin triples and hierarchies of nonlinear equations in Lax and zero curvature form.

  14. Strengthening the Regional Integration in Central and Eastern Europe through Cohesion Policy Instruments and Cooperation among Stock Exchanges

    Directory of Open Access Journals (Sweden)

    JULIA STEFANOVA

    2014-05-01

    Full Text Available The research paper is focused on the analysis of two ways of strengthening the regional integration in the Central and Eastern Europe – through the Cohesion policy instruments and cooperation among stock exchanges. Substantial benefits from the regional integration through cohesion policy include economic and social prosperity, political understanding. It should be further intensified, as it contributes to reduce regional disparities, exchange knowledge and best practices, ensure economic development. On the other hand, the deepening intra-regional cooperation among CEE stock exchanges leads to quantitative and qualitative changes in the course of their consolidation. Some assumptions are reached regarding expected changes on the Bulgarian capital market in the course of intensifying its intra-regional integrational links to CEE capital markets in conformity with set strategic priorities.

  15. Widespread expression of BDNF but not NT3 by target areas of basal forebrain cholinergic neurons

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, H.S.; Hains, J.M.; Laramee, G.R.; Rosenthal, A.; Winslow, J.W. (Genentech, San Francisco, CA (USA))

    1990-10-12

    Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) are homologs of the well-known neurotrophic factor nerve growth factor. The three members of this family display distinct patterns of target specificity. To examine the distribution in brain of messenger RNA for these molecules, in situ hybridization was performed. Cells hybridizing intensely to antisense BDNF probe were located throughout the major targets of the rat basal forebrain cholinergic system, that is, the hippocampus, amygdala, and neocortex. Strongly hybridizing cells were also observed in structures associated with the olfactory system. The distribution of NT3 mRNA in forebrain was much more limited. Within the hippocampus, labeled cells were restricted to CA2, the most medial portion of CA1, and the dentate gyrus. In human hippocampus, cells expressing BDNF and mRNA are distributed in a fashion similar to that observed in the rat. These findings point to both basal forebrain cholinergic cells and olfactory pathways as potential central targets for BDNF.

  16. Centrally patterned rhythmic activity integrated by a peripheral circuit linking multiple oscillators.

    Science.gov (United States)

    Jellies, John; Kueh, Daniel

    2012-08-01

    The central pattern generator for heartbeat in the medicinal leech, Hirudo generates rhythmic activity conveyed by heart excitor motor neurons in segments 3-18 to coordinate the bilateral tubular hearts and side vessels. We focus on behavior and the influence of previously un-described peripheral nerve circuitry. Extracellular recordings from the valve junction (VJ) where afferent vessels join the heart tube were combined with optical recording of contractions. Action potential bursts at VJs occurred in advance of heart tube and afferent vessel contractions. Transections of nerves were performed to reduce the output of the central pattern generator reaching the heart tube. Muscle contractions persisted but with a less regular rhythm despite normal central pattern generator rhythmicity. With no connections between the central pattern generator and heart tube, a much slower rhythm became manifest. Heart excitor neuron recordings showed that peripheral activity might contribute to the disruption of centrally entrained contractions. In the model presented, peripheral activity would normally modify the activity actually reaching the muscle. We also propose that the fundamental efferent unit is not a single heart excitor neuron, but rather is a functionally defined unit of about three adjacent motor neurons and the peripheral assembly of coupled peripheral oscillators.

  17. Basal ganglia cholinergic and dopaminergic function in progressive supranuclear palsy.

    Science.gov (United States)

    Warren, Naomi M; Piggott, Margaret A; Greally, Elizabeth; Lake, Michelle; Lees, Andrew J; Burn, David J

    2007-08-15

    Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative disorder. In contrast to Parkinson's disease (PD) and dementia with Lewy bodies (DLB), replacement therapy with dopaminergic and cholinergic agents in PSP has been disappointing. The neurochemical basis for this is unclear. Our objective was to measure dopaminergic and cholinergic receptors in the basal ganglia of PSP and control brains. We measured, autoradiographically, dopaminergic (dopamine transporter, 125I PE2I and dopamine D2 receptors, 125I epidepride) and cholinergic (nicotinic alpha4beta2 receptors, 125I 5IA85380 and muscarinic M1 receptors, 3H pirenzepine) parameters in the striatum and pallidum of pathologically confirmed PSP cases (n=15) and controls (n=32). In PSP, there was a marked loss of dopamine transporter and nicotinic alpha4beta2 binding in the striatum and pallidum, consistent with loss of nigrostriatal neurones. Striatal D2 receptors were increased in the caudate and muscarinic M1 receptors were unchanged compared with controls. These results do not account for the poor response to dopaminergic and cholinergic replacement therapies in PSP, and suggest relative preservation of postsynaptic striatal projection neurones bearing D2/M1 receptors. PMID:17534953

  18. Cholinergic Abnormalities, Endosomal Alterations and Up-Regulation of Nerve Growth Factor Signaling in Niemann-Pick Type C Disease

    Directory of Open Access Journals (Sweden)

    Cabeza Carolina

    2012-03-01

    Full Text Available Abstract Background Neurotrophins and their receptors regulate several aspects of the developing and mature nervous system, including neuronal morphology and survival. Neurotrophin receptors are active in signaling endosomes, which are organelles that propagate neurotrophin signaling along neuronal processes. Defects in the Npc1 gene are associated with the accumulation of cholesterol and lipids in late endosomes and lysosomes, leading to neurodegeneration and Niemann-Pick type C (NPC disease. The aim of this work was to assess whether the endosomal and lysosomal alterations observed in NPC disease disrupt neurotrophin signaling. As models, we used i NPC1-deficient mice to evaluate the central cholinergic septo-hippocampal pathway and its response to nerve growth factor (NGF after axotomy and ii PC12 cells treated with U18666A, a pharmacological cellular model of NPC, stimulated with NGF. Results NPC1-deficient cholinergic cells respond to NGF after axotomy and exhibit increased levels of choline acetyl transferase (ChAT, whose gene is under the control of NGF signaling, compared to wild type cholinergic neurons. This finding was correlated with increased ChAT and phosphorylated Akt in basal forebrain homogenates. In addition, we found that cholinergic neurons from NPC1-deficient mice had disrupted neuronal morphology, suggesting early signs of neurodegeneration. Consistently, PC12 cells treated with U18666A presented a clear NPC cellular phenotype with a prominent endocytic dysfunction that includes an increased size of TrkA-containing endosomes and reduced recycling of the receptor. This result correlates with increased sensitivity to NGF, and, in particular, with up-regulation of the Akt and PLC-γ signaling pathways, increased neurite extension, increased phosphorylation of tau protein and cell death when PC12 cells are differentiated and treated with U18666A. Conclusions Our results suggest that the NPC cellular phenotype causes neuronal

  19. Assessing incentive policies for integrating centralized solar power generation in the Brazilian electric power system

    International Nuclear Information System (INIS)

    This study assesses the impacts of promoting, through auctions, centralized solar power generation (concentrated solar power – CSP, and photovoltaic solar panels – PV) on the Brazilian power system. Four types of CSP plants with parabolic troughs were simulated at two sites, Bom Jesus da Lapa and Campo Grande, and PV plants were simulated at two other sites, Recife and Rio de Janeiro. The main parameters obtained for each plant were expanded to other suitable sites in the country (totaling 17.2 GW in 2040), as inputs in an optimization model for evaluating the impacts of the introduction of centralized solar power on the expansion of the electricity grid up to 2040. This scenario would be about USD$ 185 billion more expensive than a business as usual scenario, where expansion solely relies on least-cost options. Hence, for the country to incentivize the expansion of centralized solar power, specific auctions for solar energy should be adopted, as well as complementary policies to promote investments in R and D and the use of hybrid systems based on solar and fuels in CSP plants. - Highlights: • We assess the impacts of promoting centralized CSP and PV by auctions in Brazil. • We simulate energy scenarios with and without solar power. • Our solar scenario leads to 17 GW of solar capacity installed between 2020 and 2040. • This solar scenario is some USD$ 185 billion more expensive than the base case

  20. Measurement Levels of the Spatial Integration – Suggestions for a Central-European Factor Group

    Directory of Open Access Journals (Sweden)

    Andrea Uszkai

    2015-10-01

    Full Text Available The objective of the study is to point out, what kind of measurement methodologies and factor groups are used to determinate the depth of the spatial integration in the national and international scientific literature. Integration means in this sense the interconnection of several (spatial units (Kulcsár-Rostás, 1989; Kovács, 2001; Kiss, 2005. One of the most widely interpreted types of the integration is the economic integration, which can be applied to enterprises and spatial units as well. This study focuses on the last one and examines it at three territorial levels, distinguishing global, supranational (among national states and subnational levels. The possible measurement methods are significantly determined by the spatial levels. The paper makes some suggestions for the possible measurement method in Cenrtral-European context.

  1. Cholinergic and perfusion brain networks in Parkinson disease dementia

    Science.gov (United States)

    McKeith, Ian G.; Burn, David J.; Wyper, David J.; O'Brien, John T.; Taylor, John-Paul

    2016-01-01

    Objective: To investigate muscarinic M1/M4 cholinergic networks in Parkinson disease dementia (PDD) and their association with changes in Mini-Mental State Examination (MMSE) after 12 weeks of treatment with donepezil. Methods: Forty-nine participants (25 PDD and 24 elderly controls) underwent 123I-QNB and 99mTc-exametazime SPECT scanning. We implemented voxel principal components (PC) analysis, producing a series of PC images of patterns of interrelated voxels across individuals. Linear regression analyses derived specific M1/M4 and perfusion spatial covariance patterns (SCPs). Results: We found an M1/M4 SCP of relative decreased binding in basal forebrain, temporal, striatum, insula, and anterior cingulate (F1,47 = 31.9, p < 0.001) in cholinesterase inhibitor–naive patients with PDD, implicating limbic-paralimbic and salience cholinergic networks. The corresponding regional cerebral blood flow SCP showed relative decreased uptake in temporoparietal and prefrontal areas (F1,47 = 177.5, p < 0.001) and nodes of the frontoparietal and default mode networks (DMN). The M1/M4 pattern that correlated with an improvement in MMSE (r = 0.58, p = 0.005) revealed relatively preserved/increased pre/medial/orbitofrontal, parietal, and posterior cingulate areas coinciding with the DMN and frontoparietal networks. Conclusion: Dysfunctional limbic-paralimbic and salience cholinergic networks were associated with PDD. Established cholinergic maintenance of the DMN and frontoparietal networks may be prerequisite for cognitive remediation following cholinergic treatment in this condition. PMID:27306636

  2. ESC-Derived Basal Forebrain Cholinergic Neurons Ameliorate the Cognitive Symptoms Associated with Alzheimer’s Disease in Mouse Models

    Directory of Open Access Journals (Sweden)

    Wei Yue

    2015-11-01

    Full Text Available Degeneration of basal forebrain cholinergic neurons (BFCNs is associated with cognitive impairments of Alzheimer’s disease (AD, implying that BFCNs hold potentials in exploring stem cell-based replacement therapy for AD. However, studies on derivation of BFCNs from embryonic stem cells (ESCs are limited, and the application of ESC-derived BFCNs remains to be determined. Here, we report on differentiation approaches for directing both mouse and human ESCs into mature BFCNs. These ESC-derived BFCNs exhibit features similar to those of their in vivo counterparts and acquire appropriate functional properties. After transplantation into the basal forebrain of AD model mice, ESC-derived BFCN progenitors predominantly differentiate into mature cholinergic neurons that functionally integrate into the endogenous basal forebrain cholinergic projection system. The AD mice grafted with mouse or human BFCNs exhibit improvements in learning and memory performances. Our findings suggest a promising perspective of ESC-derived BFCNs in the development of stem cell-based therapies for treatment of AD.

  3. Delirium Accompanied by Cholinergic Deficiency and Organ Failure in a 73-Year-Old Critically Ill Patient: Physostigmine as a Therapeutic Option

    Directory of Open Access Journals (Sweden)

    Benedikt Zujalovic

    2015-01-01

    Full Text Available Delirium is a common problem in ICU patients, resulting in prolonged ICU stay and increased mortality. A cholinergic deficiency in the central nervous system is supposed to be a relevant pathophysiologic process in delirium. Acetylcholine is a major transmitter of the parasympathetic nervous system influencing several organs (e.g., heart and kidneys and the inflammatory response too. This perception might explain that delirium is not an individual symptom, but rather a part of a symptom complex with various disorders of the whole organism. The cholinergic deficiency could not be quantified up to now. Using the possibility of bedside determination of the acetylcholinesterase activity (AChE activity, we assumed to objectify the cholinergic homeostasis within minutes. As reported here, the postoperative delirium was accompanied by a massive hemodynamic and renal deterioration of unclear genesis. We identified the altered AChE activity as a plausible pathophysiological mechanism. The pharmacological intervention with the indirect parasympathomimetic physostigmine led to a quick and lasting improvement of the patient’s cognitive, hemodynamic, and renal status. In summary, severe delirium is not always an attendant phenomenon of critical illness. It might be causal for multiple organ deterioration if it is based on cholinergic deficiency and has to be treated at his pathophysiological roots whenever possible.

  4. Central Colorado Assessment Project - Application of integrated geologic, geochemical, biologic, and mineral resource studies

    Science.gov (United States)

    Klein, T.L.; Church, S.E.; Caine, J.S.; Schmidt, T.S.; deWitt, E.H.

    2008-01-01

    Central Colorado is one of the fastest-growing regions in the Western United States. Population along the Front Range increased more than 30 percent between 1990 and 2000 (http://www.demographia.com/db-metro3newworld.htm) with some counties within the study area, such as Park County, experiencing greater than 100-percent growth (http://www.censusscope.org/us/s8/rank_popl_growth.html). This growth has caused tremendous demand for natural resources and has created challenging land-management issues related to the interface between wilderness and urban expansion. Management of this wilderness/urban interface will benefit from current digital geoscience information collected by the U.S. Geological Survey (USGS) Central Colorado Assessment Project that began in 2003. Approximately 20,800 square miles (53,800 km2) of land divided almost equally between the public and private sectors were part of the assessment.

  5. Distributed control of PV strings with module integrated converters in presence of a central MPPT

    DEFF Research Database (Denmark)

    Sera, Dezso; Mathe, Laszlo; Blaabjerg, Frede

    2014-01-01

    in that the MIC should ensure the string voltage stability and MPP operation in presence of other MICs and ‘plain’ panels. It must also be transparent to the main inverters' MPPT, so that it can track during normal operation. In this paper, a system layout with local MPPT without voltage control is proposed......, which is able to ensure string voltage stability and MPP tracking in presence of a central MPPT....

  6. Internal combustion engine with a central crankshaft and integral tandem annular pistons

    Science.gov (United States)

    Esparbes, Bernard

    1993-08-01

    An internal combustion engine with tandem annular pistons and a central crankshaft is disclosed, based on that found in British patent 11027 of 11 May 1914. The piston block formed by the two pistons presents, at each axial extremity, a double axial skirt fitted with an outer crown forming the head of the piston as such, and an inner crown forming an inlet pump with a holding chamber radially located at the inside of the corresponding annular cylinder, in which the piston head delimits a combustion chamber. Radial fingers, crossing axial openings of the crankcase and radial holes of the piston block, have their inner radial ends engaged within wavy sinusoidal peripheral slots arranged in a bulging central portion of the central crankshaft set into rotation by alternating axial movements of the piston block. The admission of fuel or combustion sustaining gas is ensured axially by the extremities, valves, and openings in the end plates closing the holding chambers in which the inner crowns slide, fitted with valves to act as an inlet pump. The invention is particularly applicable to aircraft engines in view of the ease in which the shaft rotation can be adapted to such a use.

  7. Las Áreas Centrales de Montevideo: En Procura de una Revitalización Integral

    Directory of Open Access Journals (Sweden)

    María del Huerto Delgado Dopazo

    2004-01-01

    Full Text Available Comenzando por una reseña histórica acerca de la conformación y evolución de la ciudad de Montevideo, capital del Uruguay, el presente artículo profundiza en los procesos de despoblamiento y degradación que sufrieron sus áreas centrales, en las últimas décadas del siglo XX; para finalmente reseñar las acciones y programas que a partir de los ’90 se han propuesto e implementado, para revertir dichos procesos. Del análisis se desprenden las potencialidades y debilidades de áreas centrales y de las propuestas de rehabilitación planteadas y en curso. Las mismas deberían enmarcarse en una planificación estratégica participativa y consensuada por todos los actores involucrados, para lograr un desarrollo local sustentable y sostenible en el tiempo. Es fundamental, para que las áreas centrales vuelvan a ser “centros vivos” de la ciudad y reconstruir la heterogeneidad tradicional del tejido social y funcional de sus barrios, el devolverles la función residencial que han ido perdiendo, y fomentar y fortalecer la participación ciudadana en los distintos niveles de los procesos.

  8. An Integrated Model of the Cardiovascular and Central Nervous Systems for Analysis of Microgravity Induced Fluid Redistribution

    Science.gov (United States)

    Price, R.; Gady, S.; Heinemann, K.; Nelson, E. S.; Mulugeta, L.; Ethier, C. R.; Samuels, B. C.; Feola, A.; Vera, J.; Myers, J. G.

    2015-01-01

    A recognized side effect of prolonged microgravity exposure is visual impairment and intracranial pressure (VIIP) syndrome. The medical understanding of this phenomenon is at present preliminary, although it is hypothesized that the headward shift of bodily fluids in microgravity may be a contributor. Computational models can be used to provide insight into the origins of VIIP. In order to further investigate this phenomenon, NASAs Digital Astronaut Project (DAP) is developing an integrated computational model of the human body which is divided into the eye, the cerebrovascular system, and the cardiovascular system. This presentation will focus on the development and testing of the computational model of an integrated model of the cardiovascular system (CVS) and central nervous system (CNS) that simulates the behavior of pressures, volumes, and flows within these two physiological systems.

  9. Whole-Brain Monosynaptic Afferent Inputs to Basal Forebrain Cholinergic System

    Science.gov (United States)

    Hu, Rongfeng; Jin, Sen; He, Xiaobin; Xu, Fuqiang; Hu, Ji

    2016-01-01

    The basal forebrain cholinergic system (BFCS) robustly modulates many important behaviors, such as arousal, attention, learning and memory, through heavy projections to cortex and hippocampus. However, the presynaptic partners governing BFCS activity still remain poorly understood. Here, we utilized a recently developed rabies virus-based cell-type-specific retrograde tracing system to map the whole-brain afferent inputs of the BFCS. We found that the BFCS receives inputs from multiple cortical areas, such as orbital frontal cortex, motor cortex, and insular cortex, and that the BFCS also receives dense inputs from several subcortical nuclei related to motivation and stress, including lateral septum, central amygdala, paraventricular nucleus of hypothalamus, dorsal raphe, and parabrachial nucleus. Interestingly, we found that the BFCS receives inputs from the olfactory areas and the entorhinal–hippocampal system. These results greatly expand our knowledge about the connectivity of the mouse BFCS and provided important preliminary indications for future exploration of circuit function. PMID:27777554

  10. A global economic integration zone in Central Europe? Vienna-Bratislava-Györ as a laboratory for EU territorial cohesion policy

    NARCIS (Netherlands)

    Tatzberger, G.

    2006-01-01

    Central Europe is facing dramatic changes and huge challenges since the 40 years closed borders opened up. As part of central Europe the Vienna-Bratislava-Gyor area that straddles Austria, Hungary and Slovakia, faces new opportunities for co-operation and integration. The book gives a fascinating vi

  11. Functional Analysis and Preliminary Specifications for a Single Integrated Central Computer System for Secondary Schools and Junior Colleges. A Feasibility and Preliminary Design Study. Interim Report.

    Science.gov (United States)

    Computation Planning, Inc., Bethesda, MD.

    A feasibility analysis of a single integrated central computer system for secondary schools and junior colleges finds that a central computing facility capable of serving 50 schools with a total enrollment of 100,000 students is feasible at a cost of $18 per student per year. The recommended system is a multiprogrammed-batch operation. Preliminary…

  12. The Centrality of Character and Integrity Education in Kenya’s Institutions of Higher Learning

    Directory of Open Access Journals (Sweden)

    Dr. John Koskey Chang’ach

    2014-02-01

    Full Text Available Education remains an important enterprise and asset by which any society models and determines its existence. It consists in a process of propagating desirable survival skills to succeeding generations. Through education, society sets and defines its basic survival needs. Thus, besides other components such as cognitive, creative and dialogical, the overriding significance of education can be summed up in its normative definitions. This is due to the fact that its impact is to be identified in the extent to which it affects and modifies one’s behavior in society. Based on this understanding, this paper focuses on the place of character and integrity education in institutions of learning. Its aim is to define, justify and affirm the importance of character as an irreplaceable component in holistic development of learners. Being a library-based study, its data is mainly obtained from internet sources and from discussions with educationists. A purely qualitative method was adopted so as to gain deeper understanding of the pertinent issues involved in character and integrity education. Thus, the principle methods used included critical analysis, speculative and dialectic methods of investigation. On the overall, the normative essence of education is critically discussed. Similarly, an exploration of various trends in character and integrity education has been made. Finally, the role of the teacher in character education of the learner is examined. The study concludes by making practical recommendations on possible ways and avenues through which character and integrity education can be enhanced in learning institutions.

  13. Exogenous testosterone attenuates the integrated central stress response in healthy young women.

    NARCIS (Netherlands)

    Hermans, E.J.; Putman, P.; Baas, J.M.; Gecks, N.M.; Kenemans, J.L.; Honk, J. van

    2007-01-01

    Animal research has shown that the androgen steroid testosterone, the end product of the hypothalamic-pituitary-gonadal (HPG) axis, down regulates the integrated stress response at multiple levels. These effects have been demonstrated at the level of the amygdala and the bed nucleus of the stria ter

  14. The Integrative Role of Danube River in Central and Eastern Europe

    Directory of Open Access Journals (Sweden)

    Andy Pusca

    2013-08-01

    Full Text Available Source of life and welfare, the Danube River is fundamental for eastern and central European countries, and marked the history of all its cultures and civilizations. The aim of this article is to present its social, cultural, economic role and the essential and fundamental valor of biodiversity. The approach proposed in this paper is based on the recognition of the multinational and multicultural particularities in the Danube area and is focused on the analysis and the importance of the local cultural synergy. We use the pragmatic interdisciplinary paradigm and our academic observation would be impartial, objective and ethical.

  15. Las Áreas Centrales de Montevideo: En Procura de una Revitalización Integral

    OpenAIRE

    María del Huerto Delgado Dopazo

    2004-01-01

    Comenzando por una reseña histórica acerca de la conformación y evolución de la ciudad de Montevideo, capital del Uruguay, el presente artículo profundiza en los procesos de despoblamiento y degradación que sufrieron sus áreas centrales, en las últimas décadas del siglo XX; para finalmente reseñar las acciones y programas que a partir de los 90 se han propuesto e implementado, para revertir dichos procesos. Del análisis se desprenden las potencialidades y de...

  16. The Experiential Component as a Central Factor in Integrating Technology into Teaching and Research.

    OpenAIRE

    Marcelo, Marcelo

    2015-01-01

    En este trabajo nos proponemos analizar la problemática de la integración de las tecnologías en la enseñanza y en la investigación, entre docentes e investigadores pertenecientes a instituciones de enseñanza superior. El objetivo de la investigación es identificar los factores centrales que influyen en la predisposición de docentes e investigadores a integrar tecnologías en la enseñanza y en la investigación. Esta investigación se llevó a cabo mediante el seguimiento de dos cursos de capacita...

  17. From Spinal Central Pattern Generators to Cortical Network: Integrated BCI for Walking Rehabilitation

    Directory of Open Access Journals (Sweden)

    G. Cheron

    2012-01-01

    Full Text Available Success in locomotor rehabilitation programs can be improved with the use of brain-computer interfaces (BCIs. Although a wealth of research has demonstrated that locomotion is largely controlled by spinal mechanisms, the brain is of utmost importance in monitoring locomotor patterns and therefore contains information regarding central pattern generation functioning. In addition, there is also a tight coordination between the upper and lower limbs, which can also be useful in controlling locomotion. The current paper critically investigates different approaches that are applicable to this field: the use of electroencephalogram (EEG, upper limb electromyogram (EMG, or a hybrid of the two neurophysiological signals to control assistive exoskeletons used in locomotion based on programmable central pattern generators (PCPGs or dynamic recurrent neural networks (DRNNs. Plantar surface tactile stimulation devices combined with virtual reality may provide the sensation of walking while in a supine position for use of training brain signals generated during locomotion. These methods may exploit mechanisms of brain plasticity and assist in the neurorehabilitation of gait in a variety of clinical conditions, including stroke, spinal trauma, multiple sclerosis, and cerebral palsy.

  18. European integration, financial resources and the absorption of European funds in Central and Eastern European Countries

    Directory of Open Access Journals (Sweden)

    Valentin NECULITA

    2013-08-01

    Full Text Available The regional integration has the purpose to enhance the income in the region, which may be achieved through getting higher economic results by using the production factors more efficiently, increasing their mobility and benefiting from the access to a comprehensive knowledge base. This paper aims to provide insights in European integration, financial resources and, absorption of European funds. The paper proposes an analysis of financial framework by means of data and statistics provided by European institution, national statistics institutions and international statistics institutions. The financial framework is a mechanism designed to ensure a strict budgetary discipline of the maximum spending cap for each major area of European Union budget. This mechanism is drawing on the basis of political and economic priorities. One of the main objectives should be the expenditure forecasting, annual budgets, so they be situated under overall cap, knowing that achieving long-term economic growth depends on the financial incentives that the European Union can sustain.

  19. Understanding the central kinematics of globular clusters with simulated integrated-light IFU observations

    CERN Document Server

    Bianchini, Paolo; van de Ven, Glenn; Schinnerer, Eva

    2015-01-01

    The detection of intermediate mass black holes in the centres of globular clusters is highly controversial, as complementary observational methods often deliver significantly different results. In order to understand these discrepancies, we develop a procedure to simulate integral field unit (IFU) observations of globular clusters: Simulating IFU Star Cluster Observations (SISCO). The input of our software are realistic dynamical models of globular clusters that are then converted in a spectral data cube. We apply SISCO to Monte Carlo cluster simulations from Downing et al. (2010), with a realistic number of stars and concentrations. Using independent realisations of a given simulation we are able to quantify the stochasticity intrinsic to the problem of observing a partially resolved stellar population with integrated-light spectroscopy. We show that the luminosity-weighted IFU observations can be strongly biased by the presence of a few bright stars that introduce a scatter in the velocity dispersion measur...

  20. Integration Platform As Central Service Of Data Replication In Distributed Medical System

    Directory of Open Access Journals (Sweden)

    Wiesław Wajs

    2007-01-01

    Full Text Available The paper presents the application of Java Integration Platform (JIP to data replicationin the distributed medical system. After an introductory part on the medical system’s architecture,the focus shifts to a comparison of different approaches that exist with regard totransferring data between the system’s components. A description is given of the historicaldata processing and of the whole area of the JIP application to the medical system.

  1. PI3K: An Attractive Candidate for the Central Integration of Metabolism and Reproduction

    OpenAIRE

    Maricedes eAcosta-Martinez

    2012-01-01

    In neurons, as in a variety of other cell types, the enzyme phosphatidylinositol-3-kinase (PI3K) is a key intermediate that is common to the signaling pathways of a number of peripheral metabolic cues, including insulin and leptin, which are well known to regulate both metabolic and reproductive functions. In this article, I explore the possibility that PI3K is a key integrator of metabolic and neural signals regulating gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH) release a...

  2. Speciation on the rocks: integrated systematics of the Heteronotia spelea species complex (Gekkota; Reptilia from Western and Central Australia.

    Directory of Open Access Journals (Sweden)

    Mitzy Pepper

    Full Text Available The isolated uplands of the Australian arid zone are known to provide mesic refuges in an otherwise xeric landscape, and divergent lineages of largely arid zone taxa have persisted in these regions following the onset of Miocene aridification. Geckos of the genus Heteronotia are one such group, and have been the subject of many genetic studies, including H. spelea, a strongly banded form that occurs in the uplands of the Pilbara and Central Ranges regions of the Australian arid zone. Here we assess the systematics of these geckos based on detailed examination of morphological and genetic variation. The H. spelea species complex is a monophyletic lineage to the exclusion of the H. binoei and H. planiceps species complexes. Within the H. spelea complex, our previous studies based on mtDNA and nine nDNA loci found populations from the Central Ranges to be genetically divergent from Pilbara populations. Here we supplement our published molecular data with additional data gathered from central Australian samples. In the spirit of integrative species delimitation, we combine multi-locus, coalescent-based lineage delimitation with extensive morphological analyses to test species boundaries, and we describe the central populations as a new species, H. fasciolatus sp. nov. In addition, within the Pilbara there is strong genetic evidence for three lineages corresponding to northeastern (type, southern, and a large-bodied melanic population isolated in the northwest. Due to its genetic distinctiveness and extreme morphological divergence from all other Heteronotia, we describe the melanic form as a new species, H. atra sp. nov. The northeastern and southern Pilbara populations are morphologically indistinguishable with the exception of a morpho-type in the southeast that has a banding pattern resembling H. planiceps from the northern monsoonal tropics. Pending more extensive analyses, we therefore treat Pilbara H. spelea as a single species with

  3. Cholinergic signals in mouse barrel cortex during active whisker sensing.

    Science.gov (United States)

    Eggermann, Emmanuel; Kremer, Yves; Crochet, Sylvain; Petersen, Carl C H

    2014-12-11

    Internal brain states affect sensory perception, cognition, and learning. Many neocortical areas exhibit changes in the pattern and synchrony of neuronal activity during quiet versus active behaviors. Active behaviors are typically associated with desynchronized cortical dynamics. Increased thalamic firing contributes importantly to desynchronize mouse barrel cortex during active whisker sensing. However, a whisking-related cortical state change persists after thalamic inactivation, which is mediated at least in part by acetylcholine, as we show here by using whole-cell recordings, local pharmacology, axonal calcium imaging, and optogenetic stimulation. During whisking, we find prominent cholinergic signals in the barrel cortex, which suppress spontaneous cortical activity. The desynchronized state of barrel cortex during whisking is therefore driven by at least two distinct signals with opposing functions: increased thalamic activity driving glutamatergic excitation of the cortex and increased cholinergic input suppressing spontaneous cortical activity.

  4. Cholinergic Signals in Mouse Barrel Cortex during Active Whisker Sensing

    Directory of Open Access Journals (Sweden)

    Emmanuel Eggermann

    2014-12-01

    Full Text Available Internal brain states affect sensory perception, cognition, and learning. Many neocortical areas exhibit changes in the pattern and synchrony of neuronal activity during quiet versus active behaviors. Active behaviors are typically associated with desynchronized cortical dynamics. Increased thalamic firing contributes importantly to desynchronize mouse barrel cortex during active whisker sensing. However, a whisking-related cortical state change persists after thalamic inactivation, which is mediated at least in part by acetylcholine, as we show here by using whole-cell recordings, local pharmacology, axonal calcium imaging, and optogenetic stimulation. During whisking, we find prominent cholinergic signals in the barrel cortex, which suppress spontaneous cortical activity. The desynchronized state of barrel cortex during whisking is therefore driven by at least two distinct signals with opposing functions: increased thalamic activity driving glutamatergic excitation of the cortex and increased cholinergic input suppressing spontaneous cortical activity.

  5. Cholinergic receptor binding in the frontal cortex of suicide victims

    International Nuclear Information System (INIS)

    Because there is a high incidence of individuals diagnosed as having an affective disorder who subsequently commit suicide, the author thought it would be of interest to determine QNB binding in the brains of a large sample of suicide victims, and to compare the findings with a well-matched control group. Brain samples were obtained at autopsy from 22 suicide victims and 22 controls. Frontal cortex samples were diseected, frozen, and stored until assayed. Samples of tissue homogenate were incubated in duplicate with 10 concentrations of tritium-QNB. Specific binding was determined with and without atropine. The results confirmed previous studies in which no changes were noted in suicide versus control brains. While the findings neither disprove nor support the cholinergic hypothesis of depression, they do suggest that the neurochemical basis for the in vivo observations of increased responsivity of depressed individuals to muscarinic cholinergic agents might not involve changes in receptors estimated by QNB binding

  6. Inhibition of airway surface fluid absorption by cholinergic stimulation

    OpenAIRE

    Nam Soo Joo; Krouse, Mauri E.; Jae Young Choi; Hyung-Ju Cho; Wine, Jeffrey J.

    2016-01-01

    In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated ...

  7. Animal model of vascular dementia and its cholinergic mechanism

    Institute of Scientific and Technical Information of China (English)

    FAN Wen-hui; LI Lu-si; LIU Zhi-rong; ZHU Hong-yan; CHEN Kang-ning

    2001-01-01

    Objective: To establish a model of vascular dementia (VD) in aging rats and study primarily the cholinergic mechanism of hypomnesia. Methods: Chronic hypoperfusion of cerebral blood flow (CBF) in the forebrain was performed in aging rats with permanent bilateral common carotid arteries occlusion (PBCCAO). Then the rats were tested with a computerized shuttle-training case. The changes of cerebrovascular system were observed with digital subtraction angiography (DSA). The brain tissues were studied with immunohistochemical method with cholinergic acetyltransferase (ChAT) as a marker. Results: The cognitive function of rats was obviously reduced in 2 months after chronic cerebral hypoperfusion and became worse 2 months later, showing a more marked decrease of ChAT positive neurons and fibers in CA1 of the hippocampus as compared with the rats of the control, which had a significant positive correlation with memory ability. Conclusion: This rat model is successfully established to imitate human VD induced with chronic cerebral hypoperfusion. The mechanism of the hypomnesia of VD might be the impairment of cholinergic neurons in frontal cortex and hippocampus.

  8. Dysfunctional penile cholinergic nerves in diabetic impotent men

    Energy Technology Data Exchange (ETDEWEB)

    Blanco, R.; Saenz de Tejada, I.; Goldstein, I.; Krane, R.J.; Wotiz, H.H.; Cohen, R.A. (Boston Univ. School of Medicine, MA (USA))

    1990-08-01

    Impotence in the diabetic man may be secondary to a neuropathic condition of the autonomic penile nerves. The relationship between autonomic neuropathy and impotence in diabetes was studied in human corporeal tissue obtained during implantation of a penile prosthesis in 19 impotent diabetic and 15 nondiabetic patients. The functional status of penile cholinergic nerves was assessed by determining their ability to accumulate tritiated choline (34), and synthesize (34) and release (19) tritiated-acetylcholine after incubation of corporeal tissue with tritiated-choline (34). Tritiated-choline accumulation, and tritiated-acetylcholine synthesis and release were significantly reduced in the corporeal tissue from diabetic patients compared to that from nondiabetic patients (p less than 0.05). The impairment in acetylcholine synthesis worsened with the duration of diabetes (p less than 0.025). No differences in the parameters measured were found between insulin-dependent (11) and noninsulin-dependent (8) diabetic patients. The ability of the cholinergic nerves to synthesize acetylcholine could not be predicted clinically with sensory vibration perception threshold testing. It is concluded that there is a functional penile neuropathic condition of the cholinergic nerves in the corpus cavernosum of diabetic impotent patients that may be responsible for the erectile dysfunction.

  9. A cholinergic hypothesis of the unconscious in affective disorders.

    Directory of Open Access Journals (Sweden)

    Costa eVakalopoulos

    2013-11-01

    Full Text Available The interactions between distinct pharmacological systems are proposed as a key dynamic in the formation of unconscious memories underlying rumination and mood disorder, but also reflect the plastic capacity of neural networks that can aid recovery. An inverse and reciprocal relationship is postulated between cholinergic and monoaminergic receptor subtypes. M1-type muscarinic receptor transduction facilitates encoding of unconscious, prepotent behavioural repertoires at the core of affective disorders and ADHD. Behavioural adaptation to new contingencies is mediated by the classic prototype receptor: 5-HT1A (Gi/o and its modulation of m1-plasticity. Reversal of learning is dependent on increased phasic activation of midbrain monoaminergic nuclei and is a function of hippocampal theta. Acquired hippocampal dysfunction due to abnormal activation of the hypothalamic-pituitary-adrenal (HPA axis predicts deficits in hippocampal-dependent memory and executive function and further impairments to cognitive inhibition. Encoding of explicit memories is mediated by Gq/11 and Gs signalling of monoamines only. A role is proposed for the phasic activation of the basal forebrain cholinergic nucleus by cortical projections from the complex consisting of the insula and claustrum. Although controversial. recent studies suggest a common ontogenetic origin of the two structures and a functional coupling. Lesions of the region result in loss of motivational behaviour and familiarity based judgements. A major hypothesis of the paper is that these lost faculties result indirectly, from reduced cholinergic tone.

  10. Cholinergic mediation of small intestinal transit in the rat

    International Nuclear Information System (INIS)

    It has been reported that small intestinal transit (SIT) in the rat is not cholinergically mediated. The geometric mean of a marker may be a more powerful method for SIT studies. Therefore, it was their goal to evaluate the effect of muscarinic blockade in normal and prostaglandin E2 (PGE2)-enhanced SIT using this method. Male, food-fasted rats (190 to 240 g) were first dosed subcutaneously with atropine. 30 min after the atropine the rats received an oral dose of PGE2 at 5.0 mg/kg. 5 min after PGE2, a 51Cr-labeled marker was dosed intraduodenally, and a 25 min transit period followed. The results are: (1) 5.0 mg/kg of PGE2 significantly stimulates the geometric mean of the marker in agreement with previous findings and (2) atropine is inhibitory at doses as low as 0.20 mg/kg for basal SIT and 0.10 mg/kg for PGE2-stimulated SIT. This indicates (1) the rat has cholinergically mediated SIT, and (2) cholinergic activation may be important for PGE2 effects on SIT in the rat

  11. A Centralized Control and Dynamic Dispatch Architecture for File Integrity Analysis

    Directory of Open Access Journals (Sweden)

    Ronald DeMara

    2006-02-01

    Full Text Available The ability to monitor computer file systems for unauthorized changes is a powerful administrative tool. Ideally this task could be performed remotely under the direction of the administrator to allow on-demand checking, and use of tailorable reporting and exception policies targeted to adjustable groups of network elements. This paper introduces M-FICA, a Mobile File Integrity and Consistency Analyzer as a prototype to achieve this capability using mobile agents. The M-FICA file tampering detection approach uses MD5 message digests to identify file changes. Two agent types, Initiator and Examiner, are used to perform file integrity tasks. An Initiator travels to client systems, computes a file digest, then stores those digests in a database file located on write-once media. An Examiner agent computes a new digest to compare with the original digests in the database file. Changes in digest values indicate that the file contents have been modified. The design and evaluation results for a prototype developed in the Concordia agent framework are described.

  12. Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep

    OpenAIRE

    Van Dort, Christa J.; Zachs, Daniel P.; Kenny, Jonathan D.; Zheng, Shu; Goldblum, Rebecca R.; Gelwan, Noah A.; Ramos, Daniel M; Nolan, Michael A.; Wang, Karen; Weng, Feng-Ju; Lin, Yingxi; Wilson, Matthew A.; Emery N Brown

    2014-01-01

    Rapid eye movement (REM) sleep is a critical component of restful sleep, yet the mechanisms that control REM sleep are incompletely understood. Brainstem cholinergic neurons have been implicated in REM sleep regulation, but heterogeneous cell types in the area have made it difficult to determine the specific role of each population, leading to a debate about the importance of cholinergic neurons. Therefore, we selectively activated brainstem cholinergic neurons to determine their role in REM ...

  13. Aging-related deficits in orexin/hypocretin modulation of the septo-hippocampal cholinergic system

    OpenAIRE

    Stanley, Emily M.; Fadel, Jim

    2012-01-01

    The medial septum (MS) of the basal forebrain contains cholinergic neurons that project to the hippocampus, support cognitive function, and are implicated in age-related cognitive decline. Hypothalamic orexin/hypocretin neurons innervate and modulate basal forebrain cholinergic neurons and provide direct inputs to the hippocampus. However, the precise role of orexin in modulating hippocampal cholinergic transmission—and how these interactions are altered in aging—is unknown. Here, orexin A wa...

  14. Cholinergic signal activated renin angiotensin system associated with cardiovascular changes in the ovine fetus

    OpenAIRE

    Geng, Chunsong; Mao, Caiping; Wu, Lei; Cheng, Yu; Liu, Rulu; Chen, Bingxin; Chen, Ling; Zhang, Lubo; Xu, Zhice

    2010-01-01

    Aim: Cholinergic regulation is important in the control of cardiovascular and endocrine responses. The mechanisms behind cardiovascular responses induced by cholinergic activation are explored by studying hormonal systems, including renin-angiotensin and vasopressin (VP). Results: In chronically prepared fetal sheep, intravenous infusion of the cholinergic agonist carbachol increased fetal systolic, diastolic, and mean arterial pressure accompanied with bradycardia at near-term. Although int...

  15. Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-signaling cytokines in rodents.

    Science.gov (United States)

    Kanazawa, Hideaki; Ieda, Masaki; Kimura, Kensuke; Arai, Takahide; Kawaguchi-Manabe, Haruko; Matsuhashi, Tomohiro; Endo, Jin; Sano, Motoaki; Kawakami, Takashi; Kimura, Tokuhiro; Monkawa, Toshiaki; Hayashi, Matsuhiko; Iwanami, Akio; Okano, Hideyuki; Okada, Yasunori; Ishibashi-Ueda, Hatsue; Ogawa, Satoshi; Fukuda, Keiichi

    2010-02-01

    Although several cytokines and neurotrophic factors induce sympathetic neurons to transdifferentiate into cholinergic neurons in vitro, the physiological and pathophysiological roles of this remain unknown. During congestive heart failure (CHF), sympathetic neural tone is upregulated, but there is a paradoxical reduction in norepinephrine synthesis and reuptake in the cardiac sympathetic nervous system (SNS). Here we examined whether cholinergic transdifferentiation can occur in the cardiac SNS in rodent models of CHF and investigated the underlying molecular mechanism(s) using genetically modified mice. We used Dahl salt-sensitive rats to model CHF and found that, upon CHF induction, the cardiac SNS clearly acquired cholinergic characteristics. Of the various cholinergic differentiation factors, leukemia inhibitory factor (LIF) and cardiotrophin-1 were strongly upregulated in the ventricles of rats with CHF. Further, LIF and cardiotrophin-1 secreted from cultured failing rat cardiomyocytes induced cholinergic transdifferentiation in cultured sympathetic neurons, and this process was reversed by siRNAs targeting Lif and cardiotrophin-1. Consistent with the data in rats, heart-specific overexpression of LIF in mice caused cholinergic transdifferentiation in the cardiac SNS. Further, SNS-specific targeting of the gene encoding the gp130 subunit of the receptor for LIF and cardiotrophin-1 in mice prevented CHF-induced cholinergic transdifferentiation. Cholinergic transdifferentiation was also observed in the cardiac SNS of autopsied patients with CHF. Thus, CHF causes target-dependent cholinergic transdifferentiation of the cardiac SNS via gp130-signaling cytokines secreted from the failing myocardium.

  16. Cholinergic control of visual categorisation in macaques

    Directory of Open Access Journals (Sweden)

    Nikolaos C. Aggelopoulos

    2011-11-01

    Full Text Available Acetylcholine (ACh is a neurotransmitter acting via muscarinic and nicotinic receptors that is implicated in several cognitive functions and impairments, such as Alzheimer’s disease. It is believed to especially affect the acquisition of new information, which is particularly important when behaviour needs to be adapted to new situations and to novel sensory events. Categorisation, the process of assigning stimuli to a category, is a cognitive function that also involves information acquisition. The role of ACh on categorisation has not been previously studied. We have examined the effects of scopolamine, an antagonist of muscarinic ACh receptors, on visual categorisation in macaque monkeys using familiar and novel stimuli. When the peripheral effects of scopolamine on the parasympathetic nervous system were controlled for, categorisation performance was disrupted following systemic injections of scopolamine. This impairment was observed only when the stimuli that needed to be categorised had not been seen before. In other words, the monkeys were not impaired by the central action of scopolamine in categorising a set of familiar stimuli (stimuli which they had categorised successfully in previous sessions. Categorisation performance also deteriorated as the stimulus became less salient by an increase in the level of visual noise. However, scopolamine did not cause additional performance disruptions for difficult categorisation judgements at lower coherence levels. Scopolamine, therefore, specifically affects the assignment of new exemplars to established cognitive categories, presumably by impairing the processing of novel information. Since we did not find an effect of scopolamine in the categorisation of familiar stimuli, scopolamine had no significant central action on other cognitive functions such as perception, attention, memory or executive control within the context of our categorisation task.

  17. Cholinergic control of visual categorization in macaques.

    Science.gov (United States)

    Aggelopoulos, Nikolaos C; Liebe, Stefanie; Logothetis, Nikos K; Rainer, Gregor

    2011-01-01

    Acetylcholine (ACh) is a neurotransmitter acting via muscarinic and nicotinic receptors that is implicated in several cognitive functions and impairments, such as Alzheimer's disease. It is believed to especially affect the acquisition of new information, which is particularly important when behavior needs to be adapted to new situations and to novel sensory events. Categorization, the process of assigning stimuli to a category, is a cognitive function that also involves information acquisition. The role of ACh on categorization has not been previously studied. We have examined the effects of scopolamine, an antagonist of muscarinic ACh receptors, on visual categorization in macaque monkeys using familiar and novel stimuli. When the peripheral effects of scopolamine on the parasympathetic nervous system were controlled for, categorization performance was disrupted following systemic injections of scopolamine. This impairment was observed only when the stimuli that needed to be categorized had not been seen before. In other words, the monkeys were not impaired by the central action of scopolamine in categorizing a set of familiar stimuli (stimuli which they had categorized successfully in previous sessions). Categorization performance also deteriorated as the stimulus became less salient by an increase in the level of visual noise. However, scopolamine did not cause additional performance disruptions for difficult categorization judgments at lower coherence levels. Scopolamine, therefore, specifically affects the assignment of new exemplars to established cognitive categories, presumably by impairing the processing of novel information. Since we did not find an effect of scopolamine in the categorization of familiar stimuli, scopolamine had no significant central action on other cognitive functions such as perception, attention, memory, or executive control within the context of our categorization task. PMID:22110428

  18. Development of index of biotic integrity expectations for the ecoregions of Indiana. I. Central corn belt plain

    International Nuclear Information System (INIS)

    The Clean Water Act Amendments of 1987 mandate the development of biological criteria for evaluating the nation's surface waters. The requirements of Section 304(a) was implemented in Indiana to determine water resource degradation. A total of 197 headwater and wading stream sites were sampled in the Central Corn Belt Plain ecoregion in order to develop and calibrate an Index of Biotic Integrity for use in Indiana. Based on inherent variance within the ecoregion, sub-basins were established based on the concept of natural areas as recognized by Homoya et al. (1985). Site specific data; locality information; and species specific scoring criteria for tolerance classification, trophic guilds, and reproductive guilds are included in the appendix

  19. Integrating sustainable hunting in biodiversity protection in Central Africa: hot spots, weak spots, and strong spots.

    Science.gov (United States)

    Fa, John E; Olivero, Jesús; Farfán, Miguel Ángel; Márquez, Ana Luz; Vargas, Juan Mario; Real, Raimundo; Nasi, Robert

    2014-01-01

    Wild animals are a primary source of protein (bushmeat) for people living in or near tropical forests. Ideally, the effect of bushmeat harvests should be monitored closely by making regular estimates of offtake rate and size of stock available for exploitation. However, in practice, this is possible in very few situations because it requires both of these aspects to be readily measurable, and even in the best case, entails very considerable time and effort. As alternative, in this study, we use high-resolution, environmental favorability models for terrestrial mammals (N = 165) in Central Africa to map areas of high species richness (hot spots) and hunting susceptibility. Favorability models distinguish localities with environmental conditions that favor the species' existence from those with detrimental characteristics for its presence. We develop an index for assessing Potential Hunting Sustainability (PHS) of each species based on their ecological characteristics (population density, habitat breadth, rarity and vulnerability), weighted according to restrictive and permissive assumptions of how species' characteristics are combined. Species are classified into five main hunting sustainability classes using fuzzy logic. Using the accumulated favorability values of all species, and their PHS values, we finally identify weak spots, defined as high diversity regions of especial hunting vulnerability for wildlife, as well as strong spots, defined as high diversity areas of high hunting sustainability potential. Our study uses relatively simple models that employ easily obtainable data of a species' ecological characteristics to assess the impacts of hunting in tropical regions. It provides information for management by charting the geography of where species are more or less likely to be at risk of extinction from hunting. PMID:25372705

  20. Integrating in Silico and in Vitro Approaches To Predict Drug Accessibility to the Central Nervous System.

    Science.gov (United States)

    Zhang, Yan-Yan; Liu, Houfu; Summerfield, Scott G; Luscombe, Christopher N; Sahi, Jasminder

    2016-05-01

    Estimation of uptake across the blood-brain barrier (BBB) is key to designing central nervous system (CNS) therapeutics. In silico approaches ranging from physicochemical rules to quantitative structure-activity relationship (QSAR) models are utilized to predict potential for CNS penetration of new chemical entities. However, there are still gaps in our knowledge of (1) the relationship between marketed human drug derived CNS-accessible chemical space and preclinical neuropharmacokinetic (neuroPK) data, (2) interpretability of the selected physicochemical descriptors, and (3) correlation of the in vitro human P-glycoprotein (P-gp) efflux ratio (ER) and in vivo rodent unbound brain-to-blood ratio (Kp,uu), as these are assays routinely used to predict clinical CNS exposure, during drug discovery. To close these gaps, we explored the CNS druglike property boundaries of 920 market oral drugs (315 CNS and 605 non-CNS) and 846 compounds (54 CNS drugs and 792 proprietary GlaxoSmithKline compounds) with available rat Kp,uu data. The exact permeability coefficient (Pexact) and P-gp ER were determined for 176 compounds from the rat Kp,uu data set. Receiver operating characteristic curves were performed to evaluate the predictive power of human P-gp ER for rat Kp,uu. Our data demonstrates that simple physicochemical rules (most acidic pKa ≥ 9.5 and TPSA methods were investigated using multiple sets of in silico molecular descriptors. We present a random forest model with excellent predictive power (∼0.75 overall accuracy) using the rat neuroPK data set. We also observed good concordance between the structural interpretation results and physicochemical descriptor importance from the Kp,uu classification QSAR model. In summary, we propose a novel, hybrid in silico/in vitro approach and an in silico screening model for the effective development of chemical series with the potential to achieve optimal CNS exposure.

  1. Integrated hydrochemical and geophysical studies for assessment of groundwater pollution in basaltic settings in Central India.

    Science.gov (United States)

    Pujari, Paras R; Padmakar, C; SuriNaidu, L; Vaijnath, V U; Kachawe, Bhusan; Gurunadha Rao, V V S; Labhasetwar, P K

    2012-05-01

    The Pithampur Industrial sectors I, II, and III, located approximately, 45 km from Indore in Central India have emerged as one of the largest industrial clusters in the region. Various types of industries ranging from automobiles to chemicals and pharmaceuticals have been set up in the region since 1990. Most of the industries have effluent treatment plants (ETP) for treating wastewater before its disposal on land and/or in water body. The present study is an attempt to assess the groundwater quality in the watersheds surrounding these industrial sectors to develop the baseline groundwater quality in order to enable the policy makers to facilitate decisions on the development of industries in this region. The industries are located in two sub-watersheds, namely, Gambhir river sub-watershed and Chambal river sub-watershed. Geologically, the study area is located in the Deccan traps of Cretaceous to Paleocene age. The different basaltic flow units underlie clayey soils varying in thickness from 2-3 m. The aquifer is mostly of unconfined nature. Samples have been collected from a network of observation wells set up in the watersheds. The water quality analysis of the groundwater samples has been carried out six times during three hydrological cycles of 2004, 2005, and 2006. The results indicate that a few observation wells in the vicinity of the industrial clusters have very high TDS concentration and exceed the Bureau of Indian Standards (BIS) guideline for TDS concentration. The contamination of groundwater has been more severe in the Gambhir watershed as compared to the Chambal watershed. The presence of the impermeable clay layers has resulted in a slow migration of contaminants from the sources. The findings reveal that there is no significant groundwater contamination in the Pithampur industrial sectors except in the vicinity of the industrial clusters, which indicates that there is good environmental space available for the expansion of industrial units in

  2. Human responses to upright tilt: a window on central autonomic integration

    Science.gov (United States)

    Cooke, W. H.; Hoag, J. B.; Crossman, A. A.; Kuusela, T. A.; Tahvanainen, K. U.; Eckberg, D. L.

    1999-01-01

    1. We examined interactions between haemodynamic and autonomic neural oscillations during passive upright tilt, to gain better insight into human autonomic regulatory mechanisms. 2. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in nine healthy young adults. Subjects breathed in time with a metronome at 12 breaths min-1 (0.2 Hz) for 5 min each, in supine, and 20, 40, 60, 70 and 80 deg head-up positions. We performed fast Fourier transform (and autoregressive) power spectral analyses and integrated low-frequency (0.05-0.15 Hz) and respiratory-frequency (0. 15-0.5 Hz) spectral powers. 3. Integrated areas of muscle sympathetic bursts and their low- and respiratory-frequency spectral powers increased directly and significantly with the tilt angle. The centre frequency of low-frequency sympathetic oscillations was constant before and during tilt. Sympathetic bursts occurred more commonly during expiration than inspiration at low tilt angles, but occurred equally in expiration and inspiration at high tilt angles. 4. Systolic and diastolic pressures and their low- and respiratory-frequency spectral powers increased, and R-R intervals and their respiratory-frequency spectral power decreased progressively with the tilt angle. Low-frequency R-R interval spectral power did not change. 5. The cross-spectral phase angle between systolic pressures and R-R intervals remained constant and consistently negative at the low frequency, but shifted progressively from positive to negative at the respiratory frequency during tilt. The arterial baroreflex modulus, calculated from low-frequency cross-spectra, decreased at high tilt angles. 6. Our results document changes of baroreflex responses during upright tilt, which may reflect leftward movement of subjects on their arterial pressure sympathetic and vagal response relations. The intensity, but not the centre frequency of low

  3. Integrating oculomotor and perceptual training to induce a pseudofovea: A model system for studying central vision loss

    Science.gov (United States)

    Liu, Rong; Kwon, MiYoung

    2016-01-01

    People with a central scotoma often adopt an eccentric retinal location (Preferred Retinal Locus, PRL) for fixation. Here, we proposed a novel training paradigm as a model system to study the nature of the PRL formation and its impacts on visual function. The training paradigm was designed to effectively induce a PRL at any intended retinal location by integrating oculomotor control and pattern recognition. Using a gaze-contingent display, a simulated central scotoma was induced in eight normally sighted subjects. A subject's entire peripheral visual field was blurred, except for a small circular aperture with location randomly assigned to each subject (to the left, right, above, or below the scotoma). Under this viewing condition, subjects performed a demanding oculomotor and visual recognition task. Various visual functions were tested before and after training at both PRL and nonPRL locations. After 6–10 hr of the training, all subjects formed their PRL within the clear window. Both oculomotor control and visual recognition performance significantly improved. Moreover, there was considerable improvement at PRL location in high-level function, such as trigram letter-recognition, reading, and spatial attention, but not in low-level function, such as acuity and contrast sensitivity. Our results demonstrated that within a relatively short time, a PRL could be induced at any intended retinal location in normally-sighted subjects with a simulated scotoma. Our training paradigm might not only hold promise as a model system to study the dynamic nature of the PRL formation, but also serve as a rehabilitation regimen for individuals with central vision loss. PMID:27089065

  4. Age-dependent improvement in passive avoidance learning of the young chick: cholinergic mediation?

    Science.gov (United States)

    Zolman, J F; Mattingly, B A

    1982-06-01

    Cholinergic mediation of the age-dependent improvement in response suppression of the young chick was studied by determining the performance of 4-day-old chicks, pretreated with scopolamine, during passive avoidance (PA) and extinction testing. In Experiment 1, chicks were trained briefly to key peck for heat reward (prepunishment training), and then tested for PA learning under immediate, 2-sec-delayed, or no shock condition. Half of the chicks in each wing-shock (5 mA, 5 sec) condition received saline injections before prepunishment training and .5 mg/kg scopolamine injections after prepunishment training. The rest of the chicks received .5 mg/kg scopolamine injections both before and after prepunishment training. For chicks in both scopolamine groups, delaying shock onset resulted in significantly less response suppression than immediate response-contingent shock. In Experiment 2, 4-day-old chicks injected with either saline or scopolamine were trained to key peck for heat reward and then tested for resistance to extinction under either response-contingent shock or nonshock conditions. Punishment decreased the number of extinction responses for both saline and scopolamine groups of chicks. Previous studies have shown that normal 1-day-old chicks do not show a significant delay of punishment effect during PA testing and that response-contingent punishment increases the number of their responses during extinction. Hence, the results of the present experiments indicate that the age-dependent improvement in response suppression of the young chick cannot be explained solely by a significant increase in central cholinergic functioning. PMID:7096681

  5. Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system.

    Science.gov (United States)

    Sunkin, Susan M; Ng, Lydia; Lau, Chris; Dolbeare, Tim; Gilbert, Terri L; Thompson, Carol L; Hawrylycz, Michael; Dang, Chinh

    2013-01-01

    The Allen Brain Atlas (http://www.brain-map.org) provides a unique online public resource integrating extensive gene expression data, connectivity data and neuroanatomical information with powerful search and viewing tools for the adult and developing brain in mouse, human and non-human primate. Here, we review the resources available at the Allen Brain Atlas, describing each product and data type [such as in situ hybridization (ISH) and supporting histology, microarray, RNA sequencing, reference atlases, projection mapping and magnetic resonance imaging]. In addition, standardized and unique features in the web applications are described that enable users to search and mine the various data sets. Features include both simple and sophisticated methods for gene searches, colorimetric and fluorescent ISH image viewers, graphical displays of ISH, microarray and RNA sequencing data, Brain Explorer software for 3D navigation of anatomy and gene expression, and an interactive reference atlas viewer. In addition, cross data set searches enable users to query multiple Allen Brain Atlas data sets simultaneously. All of the Allen Brain Atlas resources can be accessed through the Allen Brain Atlas data portal.

  6. Integrating in Silico and in Vitro Approaches To Predict Drug Accessibility to the Central Nervous System.

    Science.gov (United States)

    Zhang, Yan-Yan; Liu, Houfu; Summerfield, Scott G; Luscombe, Christopher N; Sahi, Jasminder

    2016-05-01

    Estimation of uptake across the blood-brain barrier (BBB) is key to designing central nervous system (CNS) therapeutics. In silico approaches ranging from physicochemical rules to quantitative structure-activity relationship (QSAR) models are utilized to predict potential for CNS penetration of new chemical entities. However, there are still gaps in our knowledge of (1) the relationship between marketed human drug derived CNS-accessible chemical space and preclinical neuropharmacokinetic (neuroPK) data, (2) interpretability of the selected physicochemical descriptors, and (3) correlation of the in vitro human P-glycoprotein (P-gp) efflux ratio (ER) and in vivo rodent unbound brain-to-blood ratio (Kp,uu), as these are assays routinely used to predict clinical CNS exposure, during drug discovery. To close these gaps, we explored the CNS druglike property boundaries of 920 market oral drugs (315 CNS and 605 non-CNS) and 846 compounds (54 CNS drugs and 792 proprietary GlaxoSmithKline compounds) with available rat Kp,uu data. The exact permeability coefficient (Pexact) and P-gp ER were determined for 176 compounds from the rat Kp,uu data set. Receiver operating characteristic curves were performed to evaluate the predictive power of human P-gp ER for rat Kp,uu. Our data demonstrates that simple physicochemical rules (most acidic pKa ≥ 9.5 and TPSA < 100) in combination with P-gp ER < 1.5 provide mechanistic insights for filtering BBB permeable compounds. For comparison, six classification modeling methods were investigated using multiple sets of in silico molecular descriptors. We present a random forest model with excellent predictive power (∼0.75 overall accuracy) using the rat neuroPK data set. We also observed good concordance between the structural interpretation results and physicochemical descriptor importance from the Kp,uu classification QSAR model. In summary, we propose a novel, hybrid in silico/in vitro approach and an in silico screening model for the

  7. PI3K: An attractive candidate for the central integration of metabolism and reproduction

    Directory of Open Access Journals (Sweden)

    Maricedes eAcosta-Martinez

    2012-01-01

    Full Text Available In neurons, as in a variety of other cell types, the enzyme phosphatidylinositol-3-kinase (PI3K is a key intermediate that is common to the signaling pathways of a number of peripheral metabolic cues, including insulin and leptin, which are well known to regulate both metabolic and reproductive functions. In this article, I explore the possibility that PI3K is a key integrator of metabolic and neural signals regulating gonadotropin releasing hormone (GnRH/luteinizing hormone (LH release and explore the hypothesis that this enzyme is pivotal in many disorders where gonadotropin release is at risk. Although the mechanisms mediating the influence of metabolism and nutrition on fertility are currently unclear, the strong association between metabolic disorders and infertility is undeniable. For example, women suffering from anorectic disorders experience amenorrhea as a consequence of malnutrition-induced impairment of LH release, and at the other extreme, obesity is also commonly co-morbid with menstrual dysfunction and infertility. Impaired hypothalamic insulin and leptin receptor signaling is thought to be at the core of reproductive disorders associated with metabolic dysfunction. While low levels of leptin and insulin characterize states of negative energy balance, prolonged nutrient excess is associated with insulin and leptin resistance. Metabolic models known to alter GnRH/LH release such as diabetes, diet-induced obesity, and caloric restriction are also accompanied by impairment of PI3K signaling in insulin and leptin sensitive tissues including the hypothalamus. However, a clear link between this signaling pathway and the control of GnRH release by peripheral metabolic cues has not been established. Investigating the role of the signaling pathways shared by metabolic cues that are critical for a normal reproductive state can help identify possible targets in the treatment of metabolic and reproductive disorders such as Polycystic Ovarian

  8. Inside the polygonal walls of Amelia (Central Italy): A multidisciplinary data integration, encompassing geodetic monitoring and geophysical prospections

    Science.gov (United States)

    Ercoli, M.; Brigante, R.; Radicioni, F.; Pauselli, C.; Mazzocca, M.; Centi, G.; Stoppini, A.

    2016-04-01

    We investigate a portion of the ancient (VI and IV centuries BC) polygonal walls of Amelia, in Central Italy. After the collapse of a portion of the walls which occurred in January 2006, a wide project started in order to monitor their external facade and inspect the characteristics of the internal structure, currently not clearly known. In this specific case, the preservation of such an important cultural heritage was mandatory, therefore invasive methods like drilling or archaeological essays cannot be used. For this purpose, a multidisciplinary approach represents an innovative way to shed light on their inner structure. We combine several non-invasive techniques such as Ground Penetrating Radar (GPR) and Electrical Resistivity Tomography (ERT), specifically adapted for this study, Laser Scanning and Digital Terrestrial Photogrammetry, integrated with other geomatic measures provided by a Total Station and Global Navigation Satellite Systems (GNSS). After collecting some historical information, we gather the whole datasets exploring for their integration an interpretation approach borrowed from the reflection seismic (attribute analysis and three dimensional visualization). The results give rise for the first time to the internal imaging of this ancient walls, highlighting features associable to different building styles related to different historical periods. Among the result, we define a max wall thickness of about 3.5 m for the cyclopic sector, we show details of the internal block organization and we detect low resistivity values interpretable with high water content behind the basal part of the walls. Then, quantitative analyses to assess their reliable geotechnical stability are done, integrating new geometrical constrains provided by the geophysics and geo-technical ground parameters available in literature. From this analysis, we highlight how the Amelia walls are interested, in the investigated sector, by a critical pseudo-static equilibrium.

  9. New concepts of the central control of reproduction, integrating influence of stress, metabolic state, and season.

    Science.gov (United States)

    Clarke, I J; Arbabi, L

    2016-07-01

    negative energy balance; this may be the cause of lowered GnRH and gonadotropin secretion in this state. There is a complex interaction between appetite-regulating peptide neurons and kisspeptin neurons that enables the former to regulate the latter both positively and negatively. In terms of how GnRH secretion is reduced during stress, recent data indicate that GnIH cells are integrally involved, with increased input to the GnRH cells. The secretion of GnIH into the portal blood is not increased during stress, so the negative effect is most likely effected at the level of GnRH neuronal cell bodies. PMID:27345314

  10. Hippocampal formation is involved in movement selection: evidence from medial septal cholinergic modulation and concurrent slow-wave (theta rhythm) recording.

    Science.gov (United States)

    Oddie, S D; Kirk, I J; Whishaw, I Q; Bland, B H

    1997-11-01

    Hippocampal rhythmical slow-wave field activity which occurs in response to sensory stimulation is predominantly cholinergic (atropine-sensitive theta rhythm), can precede movement initiation, and co-occurs during non-cholinergic theta rhythm associated with ongoing movement (atropine-resistant). This relationship suggests that theta rhythm plays some role in movement control. The present naturalistic experiments tested the idea that atropine-sensitive theta rhythm plays a role in sensory integration and planning required for initiating appropriate movements. One of a pair of hungry rats, the victim, implanted with hippocampal field recording electrodes, a septal injection cannula, and a posterior hypothalamic stimulating electrode, was given food which the other, the robber, tries to steal. Since the victim dodges from the robber with a latency, distance, and velocity dependent upon the size of the food, elapsed eating time, and proximity of the robber, the movement requires sensory integration and planning. Although eating behavior seemed normal, atropine-sensitive theta rhythm and dodging were disrupted by an infusion of a cholinergic antagonist into the medial septum. When the victim in turn attempted to steal the food back, Type 1 theta rhythm was present and robbery attempts seemed normal. Prior to cholinergic blockade, posterior hypothalamic stimulation produced theta rhythm and dodges, even in the absence of the robber, but following injections, atropine-sensitive theta rhythm and dodging were absent as the animals dropped the food and ran. The results provide the first evidence to link atropine-sensitive theta rhythm and hippocampal structures to a role in sensory integration and planning for the initiation of movement. PMID:9404626

  11. Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia

    Science.gov (United States)

    Dobrovinskaya, Oxana; Valencia-Cruz, Georgina; Castro-Sánchez, Luis; Bonales-Alatorre, Edgar O.; Liñan-Rico, Liliana; Pottosin, Igor

    2016-01-01

    Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells. Cell lines derived from acute lymphoblastic leukemias of T lineage (T-ALL) were found to produce a considerably higher amount of ACh than healthy T lymphocytes. Additionally, ACh produced by T-ALL is not efficiently hydrolyzed, because acetylcholinesterase (AChE) activity is drastically decreased in these cells. Up-regulation of muscarinic ACh receptors was also demonstrated at expression and functional level, whereas nicotinic ACh receptors seem to play a less important role and not form functional channels in cells derived from T-ALL. We hypothesized that ACh over-produced in T-ALL may act as an autocrine growth factor and play an important role in leukemic clonal expansion through shaping of intracellular Ca2+ signals. We suggest that cholinergic machinery may be attractive targets for new drugs against T-ALL. Specifically, testing of high affinity antagonists of muscarinic ACh receptors as well as antagomiRs, which interfere with miRNAs involved in the suppression of AChE expression, may be the first choice options. PMID:27630569

  12. Novel aspects of cholinergic regulation of colonic ion transport.

    Science.gov (United States)

    Bader, Sandra; Diener, Martin

    2015-06-01

    Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiments with putative nicotinic agonists and antagonists were performed at rat colon combined with reverse transcription polymerase chain reaction (RT-PCR) detection of nicotinic receptor subunits within the epithelium. Dimethylphenylpiperazinium (DMPP) and nicotine induced a tetrodotoxin-resistant anion secretion leading to an increase in short-circuit current (I sc) across colonic mucosa. The response was suppressed by the nicotinic receptor antagonist hexamethonium. RT-PCR experiments revealed the expression of α2, α4, α5, α6, α7, α10, and β4 nicotinic receptor subunits in colonic epithelium. Choline, the product of acetylcholine hydrolysis, is known for its affinity to several nicotinic receptor subtypes. As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on I sc was examined. Choline induced a concentration-dependent, tetrodotoxin-resistant chloride secretion which was, however, resistant against hexamethonium, but was inhibited by atropine. Experiments with inhibitors of muscarinic M1 and M3 receptors revealed that choline-evoked secretion was mainly due to a stimulation of epithelial M3 receptors. Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion. Thus the cholinergic regulation of colonic ion transport - up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors - is more complex than previously assumed. PMID:26236483

  13. Cholinergic neurons in the dorsomedial hypothalamus regulate mouse brown adipose tissue metabolism

    Directory of Open Access Journals (Sweden)

    Jae Hoon Jeong

    2015-06-01

    Conclusion: DMH cholinergic neurons directly send efferent signals to sympathetic premotor neurons in the Rpa. Elevated cholinergic input to this area reduces BAT activity through activation of M2 mAChRs on serotonergic neurons. Therefore, the direct DMHACh–Rpa5-HT pathway may mediate physiological heat-defense responses to elevated environmental temperature.

  14. Ultrastructural localization of cholinergic muscarinic receptors in rat brain cortical capillaries

    NARCIS (Netherlands)

    Luiten, PGM; deJong, GI; VanderZee, EA; vanDijken, H; Dijken, H. van

    1996-01-01

    Cholinergic innervation of the cerebrovasculature is known to regulate vascular tone, perfusion rate and permeability of the microvascular wall. Notably the cholinergic innervation of cerebral capillaries is of interest since these capillaries form the blood-brain barrier. Although there is a genera

  15. Mechanisms mediating cholinergic antral circular smooth muscle contraction in rats

    Institute of Scientific and Technical Information of China (English)

    Helena F Wrzos; Tarun Tandon; Ann Ouyang

    2004-01-01

    AIM: To investigate the pathway (s) mediating rat antral circular smooth muscle contractile responses to the cholinomimetic agent, bethanechol and the subtypes of muscarinic receptors mediating the cholinergic contraction.METHODS: Circular smooth muscle strips from the antrum of Sprague-Dawley rats were mounted in muscle baths in Krebs buffer. Isometric tension was recorded. Cumulative concentration-response curves were obtained for (+)-cisdioxolane (cD), a nonspecific muscarinic agonist, at 10-8-10-4 mol/L, in the presence of tetrodotoxin (TTX, 10-7 mol/L).Results were normalized to cross sectional area. A repeat concentration-response curve was obtained after incubation of the muscle for 90 min with antagonists for M1 (pirenzepine),M2 (methoctramine) and M3 (darifenacin) muscarinic receptor subtypes. The sensitivity to PTX was tested by the ip injection of 100 mg/kg of PTX 5 d before the experiment. The antral circular smooth muscles were removed from PTX-treated and non-treated rats as strips and dispersed smooth muscle cells to identify whether PTX-linked pathway mediated the contractility to bethanechol.RESULTS: A dose-dependent contractile response observed with bethanechol, was not affected by TTX. The pretreatment of rats with pertussis toxin decreased the contraction induced by bethanechol. Lack of calcium as Well as the presence of the L-type calcium channel blocker, nifedipine, also inhibited the cholinergic contraction, with a reduction in response from 2.5±0.4 g/mm2 to 1.2±0.4 g/mm2 (P<0.05). The doseresponse curves were shifted to the right by muscarinic antagonists in the following order of affinity: darifenacin(M3)>methocramine (M2)>pirenzepine (M1).CONCLUSION: The muscarinic receptors-dependent contraction of rat antral circular smooth muscles was linked to the signal transduction pathway(s) involving pertussis-toxin sensitive GTP-binding proteins and to extracellular calcium via L-type voltage gated calcium channels. The presence of the

  16. Lessons learned from the integration of local stakeholders in water management approaches in central-northern Namibia

    Science.gov (United States)

    Jokisch, A.; Urban, W.

    2012-04-01

    Water is the main limiting factor for economic and agricultural development in central-northern Namibia, where approximately 50% of the Namibian population lives on less than 10% of the country's surface area. The climate in the region can be characterized as semi-arid, with distinctive rainy and dry seasons and an average precipitation of 470 mm/a. Central-northern Namibia can furthermore be characterized by a system of so-called Oshanas, very shallow ephemeral river streams which drain the whole region from north to south towards the Etosha-Saltpan. Water quality within these ephemeral river streams rapidly decreases towards the end of the dry season due to high rates of evaporation (2,700 mm/a) which makes the water unsuitable for human consumption and in certain times of the year also for irrigation purposes. Other local water resources are scarce or of low quality. Therefore, the local water supply is mainly secured via a pipeline scheme which is fed by the Namibian-Angolan border river Kunene. Within the research project CuveWaters - Integrated Water Resources Management in central-northern Namibia different small scale water supply and sanitation technologies are implemented and tested as part of the projects multi-resource mix. The aim is to decentralize the regional water supply and make it more sustainable especially in the face of climate change. To gain understanding and to create ownership within the local population for the technologies implemented, stakeholder participation and capacity development are integral parts of the project. As part of the implementation process of rainwater harvesting and water harvesting from ephemeral river streams, pilot plants for the storage of water were constructed with the help of local stakeholders who will also be the beneficiaries of the pilot plants. The pilot plants consist of covered storage tanks and infrastructure for small scale horticultural use of the water stored. These small scale horticultural

  17. Linking Cholinergic Interneurons, Synaptic Plasticity, and Behavior during the Extinction of a Cocaine-Context Association.

    Science.gov (United States)

    Lee, Junuk; Finkelstein, Joel; Choi, Jung Yoon; Witten, Ilana B

    2016-06-01

    Despite the fact that cholinergic interneurons are a key cell type within the nucleus accumbens, a relationship between synaptic plasticity and the in vivo activity of cholinergic interneurons remains to be established. Here, we identify a three-way link between the activity of cholinergic interneurons, synaptic plasticity, and learning in mice undergoing the extinction of a cocaine-context association. We found that activity of cholinergic interneurons regulates extinction learning for a cocaine-context association and generates a sustained reduction in glutamatergic presynaptic strength onto medium spiny neurons. Interestingly, activation of cholinergic interneurons does not support reinforcement learning or plasticity by itself, suggesting that these neurons have a modulatory rather than a reinforcing function. PMID:27210555

  18. Cholinergic deficiency involved in vascular dementia:possible mechanism and strategy of treatment

    Institute of Scientific and Technical Information of China (English)

    Juan WANG; Hai-yan ZHANG; Xi-can TANG

    2009-01-01

    Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence.Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment.Moreover,cholinergic therapies have shown promising effects on cognitive improvement in VaD patients.The precise mechanisms of these cholinergic agents are currently not fully understood;however,accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway,in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation,although regulation of oxidative stress and energy metabolism,alleviation of apoptosis may also be involved.In this paper,we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

  19. Integrated geophysical and geological studies of selected major tectonic features in south-central U.S

    Science.gov (United States)

    Alrefaee, Hamed

    The current dissertation includes three separate chapters, each utilizing the power of the integration of different geophysical datasets with geology to investigate tectonic and structural processes responsible for the geological evolution of selected major tectonic features in south-central U. S. These tectonic features are; the Arkoma basin of Oklahoma and Arkansas, the Llano uplift of central Texas, and the Meers fault of the southwestern Oklahoma. The Arkoma basin is an arcuate structural feature that extends from the Gulf coastal plain in central Arkansas westward 400 km to the Arbuckle Mountains in south-central Oklahoma. The interpretation of the 3-D seismic data reveals an E-W zone of crustal weakness in the northern part of the study area, which could be a Late Paleozoic tectonic inversion of the extension faulting that developed during Cambrian rifting and later foreland basin development. The seismic interpretation reveals a compressive deformation of the Late Paleozoic strata related to the Ouachita orogeny. Magnetic boundaries such as faults andor body edges extending E-W, NE-SW and NW-SE have been delineated using magnetic edge detector techniques in the northern, southeastern, and western parts of the study area, respectively. The Euler magnetic depth estimation method delineated the same faults determined using magnetic edge detector techniques. The maximum depth to faults dominating the basement and/or the intrabasement features determined by the Euler's method is about 3850 m. The fault trends delineated by the seismic interpretation and those determined by the Euler's method and the edge detector techniques show a very clear correlation. The Llano Uplift is a broad structural dome in central Texas with 2 to 3 km of structural relief relative to the subsurface Fort Worth and Kerr basins to the northeast and southwest. The initial uplift due to an arc-continent collision was followed by a continent-continent collision between the Laurentia and a

  20. The cholinergic anti-inflammatory pathway delays TLR-induced skin allograft rejection in mice: cholinergic pathway modulates alloreactivity.

    Directory of Open Access Journals (Sweden)

    Claude Sadis

    Full Text Available Activation of innate immunity through Toll-like receptors (TLR can abrogate transplantation tolerance by revealing hidden T cell alloreactivity. Separately, the cholinergic anti-inflammatory pathway has the capacity to dampen macrophage activation and cytokine release during endotoxemia and ischemia reperfusion injury. However, the relevance of the α7 nicotinic acetylcholine receptor (α7nAChR-dependent anti-inflammatory pathway in the process of allograft rejection or maintenance of tolerance remains unknown. The aim of our study is to investigate whether the cholinergic pathway could impact T cell alloreactivity and transplant outcome in mice. For this purpose, we performed minor-mismatched skin allografts using donor/recipient combinations genetically deficient for the α7nAChR. Minor-mismatched skin grafts were not rejected unless the mice were housed in an environment with endogenous pathogen exposure or the graft was treated with direct application of imiquimod (a TLR7 ligand. The α7nAChR-deficient recipient mice showed accelerated rejection compared to wild type recipient mice under these conditions of TLR activation. The accelerated rejection was associated with enhanced IL-17 and IFN-γ production by alloreactive T cells. An α7nAChR-deficiency in the donor tissue facilitated allograft rejection but not in recipient mice. In addition, adoptive T cell transfer experiments in skin-grafted lymphopenic animals revealed a direct regulatory role for the α7nAChR on T cells. Taken together, our data demonstrate that the cholinergic pathway regulates alloreactivity and transplantation tolerance at multiple levels. One implication suggested by our work is that, in an organ transplant setting, deliberate α7nAChR stimulation of brain dead donors might be a valuable approach for preventing donor tissue inflammation prior to transplant.

  1. Integration of geophysical and geological data for delimitation of mineralized zones in Um Naggat area, Central Eastern Desert, Egypt

    Science.gov (United States)

    Gaafar, Ibrahim

    2015-06-01

    An integrated approach for geophysical, geological and mineralogical data was followed for Um Naggat area, Central Eastern Desert, Egypt, in order to delineate its mineralized zones. The albitized granites are well-defined on the Th- and U-channel images, by their anomalous shapes, reaching 150 ppm and 90 ppm respectively, beside low K content. Interpretations of the aeromagnetic maps delineated four regional structural trends oriented due NNW, NW, ENE and E-W directions. They are identified as strike-slip faults, which coincide well with field observations, where NW-trending faults cut and displace right laterally ENE-trending older ones. The interaction between these two strike-slip fault systems confining the albite granite is easily identified on the regional data presenting longer wavelength anomalies, implying deep-seated structures. They could represent potential pathways for migration of enriched mineralized fluids. Geochemically, albite granites of peraluminous characteristics that had suffered extensive post-magmatic metasomatic reworking, resulted into development of (Zr, Hf, Nb, Ta, U, Th, Sn) and albite-enriched and greisenized granite body of about 600 m thick, and more than 3 km in strike length. The albite granite is characterized by sharp increase in average rare metal content: Zr (830 ppm), Hf (51 ppm), Nb (340 ppm), Ta (44 ppm), and U (90 ppm). Thorite, uranothorite, uraninite and zircon are the main uranium-bearing minerals of magmatic origin within the enclosing granite. However, with respect to Zr, Nb, and Ta, the albitized granite can be categorized as rare metal granite. The integration of airborne geophysical (magnetic and γ-ray spectrometric), geological, geochemical and mineralogical data succeeded in assigning the albite granite of Um Naggat pluton as a mineralized zone. This zone is characterized by its high thorium and uranium of hydrothermal origin as indicated by its low Th/U ratio, with rare metals mineralization controlled by two

  2. Somatostatin modulates cholinergic neurotransmission in canine antral muscle

    International Nuclear Information System (INIS)

    Somatostatin has been shown to inhibit antral motility in vivo. To examine the effect of somatostatin on cholinergic neurotransmission in the canine antrum, we studied the mechanical response of and the release of [3H]acetylcholine from canine longitudinal antral muscle in response to substance P, gastrin 17, and electrical stimulation. In unstimulated tissues, somatostatin had a positive inotropic effect on spontaneous phasic contractions. In tissues stimulated with substance P and gastrin 17, but not with electrical stimulation, somatostatin inhibited the phasic inotropic response dose dependently. This inhibitory effect was abolished by indomethacin. Somatostatin stimulated the release of prostaglandin E2 radioimmunoreactivity, and prostaglandin E2 inhibited the release of [3H]acetylcholine induced by substance P and electrical stimulation. Somatostatin increased the release of [3H]acetylcholine from unstimulated tissues by a tetrodotoxin-sensitive mechanism but inhibited the release induced by substance P and electrical stimulation. These results suggest that somatostatin has a dual modulatory effect on cholinergic neutrotransmission in canine longitudinal antral muscle. This effect is excitatory in unstimulated tissues and inhibitory in stimulated tissues. The inhibitory effect is partially mediated by prostaglandins

  3. Quantifying Freshwater Mass Balance in the Central Tibetan Plateau by Integrating Satellite Remote Sensing, Altimetry, and Gravimetry

    Directory of Open Access Journals (Sweden)

    Kuo-Hsin Tseng

    2016-05-01

    Full Text Available The Tibetan Plateau (TP has been observed by satellite optical remote sensing, altimetry, and gravimetry for a variety of geophysical parameters, including water storage change. However, each of these sensors has its respective limitation in the parameters observed, accuracy and spatial-temporal resolution. Here, we utilized an integrated approach to combine remote sensing imagery, digital elevation model, and satellite radar and laser altimetry data, to quantify freshwater storage change in a twin lake system named Chibuzhang Co and Dorsoidong Co in the central TP, and compared that with independent observations including mass changes from the Gravity Recovery and Climate Experiment (GRACE data. Our results show that this twin lake, located within the Tanggula glacier system, remained almost steady during 1973–2000. However, Dorsoidong Co has experienced a significant lake level rise since 2000, especially during 2000–2005, that resulted in the plausible connection between the two lakes. The contemporary increasing lake level signal at a rate of 0.89 ± 0.05 cm·yr−1, in a 2° by 2° grid equivalent water height since 2002, is higher than the GRACE observed trend at 0.41 ± 0.17 cm·yr−1 during the same time span. Finally, a down-turning trend or inter-annual variability shown in the GRACE signal is observed after 2012, while the lake level is still rising at a consistent rate.

  4. Serum Anticholinergic Activity: A Possible Peripheral Marker of the Anticholinergic Burden in the Central Nervous System in Alzheimer’s Disease

    OpenAIRE

    Koji Hori; Kimiko Konishi; Masayuki Tani; Hiroi Tomioka; Ryo Akita; Yuka Kitajima; Mari Aoki; Sachiko Yokoyama; Kazunari Azuma; Daisuke Ikuse; Norihisa Akashi; Misa Hosoi; Koichi Jinbo; Mitsugu Hachisu

    2014-01-01

    We review the utility of serum anticholinergic activity (SAA) as a peripheral marker of anticholinergic activity (AA) in the central nervous system (CAA). We hypothesize that the compensatory mechanisms of the cholinergic system do not contribute to SAA if their system is intact and that if central cholinergic system deteriorates alone in conditions such as Alzheimer’s disease or Lewy body dementia, CAA and SAA are caused by way of hyperactivity of inflammatory system and SAA is a marker of t...

  5. Trade Policies in Central Asia after EU Enlargement and before Russian WTO Accession: Regionalism and Integration into the World Economy

    OpenAIRE

    Richard Pomfret

    2004-01-01

    This paper analyses the choices between regionalism and multilateralism, and the impact of WTO membership on the five Central Asian countries. The two main sections analyse (1) why the large number of regional trade agreements which the Central Asian countries have signed have had little economic impact, and (2) the consequences for the Central Asian countries of Chinese and Russian WTO membership and the consequences of the current Central Asian applicants’ (Kazakhstan, Tajikistan and Uzbeki...

  6. Reconstruction of cryospheric changes in the Maipo and Juncal river basins, central Andes of Chile: an integrative geomorphological approach

    Science.gov (United States)

    Nussbaumer, Samuel U.; García, Juan L.; Gómez, Gabriel; Vega, Rodrigo M.; Gärtner-Roer, Isabelle; Salzmann, Nadine

    2016-04-01

    Water in the central Andes (32-38° S), a semi-arid mountainous area with elevations over 6000 m asl., is of great importance and a critical resource especially in the dry summer months. Ice bodies, such as glaciers and rock glaciers (permafrost) in the high mountains, provide a substantial part of the fresh-water resources but also for intensive economical use for the lowlands including Santiago metropolitan region, Chile. However the evolution of these ice bodies since the last deglaciation (i.e., Holocene, last ˜12,000 years), and in particular during historical times, and their feedback with climate is fairly unknown. In view of projected climate change, this is striking because it is also unknown whether these natural resources could be used as sustainable fresh-water source in the future. Within the presented project, we develop and apply an integrative geomorphologic approach to study glaciers and their long-term evolution in the central Andes of Chile. Apart from glaciers (with variable debris-coverage), rock glaciers have evolved over time as striking geomorphological landforms in this area. We combine geomorphologic mapping using remote-sensing and in-situ data with an innovative surface exposure dating technique to determine the ages of distinct moraine ridges at three study sites in watersheds of the Santiago region: Juncal Norte, Loma Larga and Nieves Negras glaciers. First results of the project are presented, including a detailed geomorphological mapping and first analysis of the landform dynamics. At all three sites, we distinguished at least three moraine systems of a Holocene putative age. These prominent moraine belts show that glaciers were at least 5 km longer than at present. Deglaciation from these ice marginal positions was gradual and complex in response to the detrital cover on the glaciers. Differences in ice thickness of the main glaciers in the respective valleys amount to about 100 m. Due to the partial, extensive debris coverage, the

  7. Involvement of dopaminergic and cholinergic pathways in the induction of yawning and genital grooming by the aqueous extract of Saccharum officinarum L. (sugarcane) in rats.

    Science.gov (United States)

    Gamberini, Maria T; Gamberini, Maria C; Nasello, Antonia G

    2015-01-01

    Yawning, associated with genital grooming, is a physiological response that may be used for elucidating the mechanism of action of drugs. Preliminary analysis showed that aqueous extract (AE) of Saccharum induced yawns in rats. So, we aimed to quantify these behavioral responses and investigate the pharmacological mechanisms involved in these actions. During 120 min, after AE administration, the yawns and the genital grooming were quantified at 10 min intervals. Since dopaminergic and cholinergic pathways are implied in these responses, AE were evaluated in the presence of haloperidol 0.5 mg/kg and atropine 2 mg/kg. AE 0.5 g/kg increased the yawns, effect that was blocked both by haloperidol and atropine. Genital grooming could only be stimulated by AE 0.5 g/kg when dopaminergic receptors were blocked by haloperidol. However, it was inhibited when atropine was previously administered. So, we demonstrated a central action of Saccharum and it was postulated that neural circuits with the participation of dopaminergic and cholinergic pathways are involved. The fact that AE is comprised of innumerous compounds could justify the extract's distinct responses. Also, we cannot disregard the presence of different neural circuits that count on the participation of dopaminergic and cholinergic pathways and could be activated by the same induction agent.

  8. Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage.

    Science.gov (United States)

    He, Yifan; Zhu, Jihong; Huang, Fang; Qin, Liu; Fan, Wenguo; He, Hongwen

    2014-11-15

    The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer's disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer's disease, and indicate that

  9. Integrative taxonomy of the Russet Bush Warbler Locustella mandelli complex reveals a new species from central China

    Institute of Scientific and Technical Information of China (English)

    Per Alström; Tianlong Cai1; Paul I Holt; Hung Le Manh; Gang Song; Yang Liu; Yanyun Zhang; Fumin Lei; Canwei Xia; Pamela C Rasmussen; Urban Olsson; Bo Dai; Jian Zhao; Paul J Leader; Geoff J Carey; Lu Dong

    2015-01-01

    Background:The Russet Bush Warbler Locustel a (previously Bradypterus) mandel i complex occurs in mountains in the eastern Himalayas, southern China, Vietnam, the Philippines, and Indonesia. The taxonomy has been debated, with one (L. seebohmi) to four (L. seebohmi, L. mandel i, L. montis and L. timorensis) species having been recognised. Methods:We used an integrative approach, incorporating analyses of morphology, vocalizations and a molecular marker, to re-evaluate species limits in the L. mandel i complex. Results:We found that central Chinese L. mandel i differed from those from India through northern Southeast Asia to southeast China in plumage, morphometrics and song. All were easily classified by song, and (wing+culmen)/tail ratio overlapped only marginally. Both groups were reciprocally monophyletic in a mitochondrial cytochrome b (cytb) gene tree, with a mean divergence of 1.0 ± 0.2%. They were sympatric and mostly altitudinally segregated in the breeding season in southern Sichuan province. We found that the Mt Victoria (western Myanmar) population differed vocally from other L. mandel i, but no specimens are available. Taiwan Bush Warbler L. alishanensis was sister to the L. mandel i complex, with the most divergent song. Plumage, vocal and cytb evidence supported the distinctness of the south Vietnamese L. mandel i idonea. The Timor Bush Warbler L. timorensis, Javan Bush Warbler L. montis and Benguet Bush Warbler L. seebohmi differed distinctly in plumage, but among-population song variation in L. montis exceeded the differences between some populations of these taxa, and mean pairwise cytb divergences were only 0.5–0.9%. We also found that some L. montis populations differed morphologically. Conclusions:We conclude that the central Chinese population of Russet Bush Warbler represents a new species, which we describe herein, breeding at mid elevations in Sichuan, Shaanxi, Hubei, Hunan and Guizhou provinces. The taxonomic status of the other

  10. Integrative taxonomy of the Russet Bush Warbler Locustella mandelli complex reveals a new species from central China

    Institute of Scientific and Technical Information of China (English)

    Per; Alstr?m; Canwei; Xia; Pamela; C; Rasmussen; Urban; Olsson; Bo; Dai; Jian; Zhao; Paul; J; Leader; Geoff; J; Carey; Lu; Dong; Tianlong; Cai; Paul; I; Holt; Hung; Le; Manh; Gang; Song; Yang; Liu; Yanyun; Zhang; Fumin; Lei

    2015-01-01

    Background: The Russet Bush Warbler Locustella(previously Bradypterus) mandelli complex occurs in mountains in the eastern Himalayas, southern China, Vietnam, the Philippines, and Indonesia. The taxonomy has been debated,with one(L. seebohmi) to four(L. seebohmi, L. mandelli, L. montis and L. timorensis) species having been recognised.Methods: We used an integrative approach, incorporating analyses of morphology, vocalizations and a molecular marker, to re-evaluate species limits in the L. mandelli complex.Results: We found that central Chinese L. mandelli differed from those from India through northern Southeast Asia to southeast China in plumage, morphometrics and song. All were easily classified by song, and(wing + culmen)/tail ratio overlapped only marginally. Both groups were reciprocally monophyletic in a mitochondrial cytochrome b(cytb) gene tree, with a mean divergence of 1.0 ± 0.2%. They were sympatric and mostly altitudinally segregated in the breeding season in southern Sichuan province. We found that the Mt Victoria(western Myanmar) population differed vocally from other L. mandelli, but no specimens are available. Taiwan Bush Warbler L. alishanensis was sister to the L. mandelli complex, with the most divergent song. Plumage, vocal and cytb evidence supported the distinctness of the south Vietnamese L. mandelli idonea. The Timor Bush Warbler L. timorensis, Javan Bush Warbler L.montis and Benguet Bush Warbler L. seebohmi differed distinctly in plumage, but among-population song variation in L. montis exceeded the differences between some populations of these taxa, and mean pairwise cytb divergences were only 0.5–0.9%. We also found that some L. montis populations differed morphologically.Conclusions: We conclude that the central Chinese population of Russet Bush Warbler represents a new species,which we describe herein, breeding at mid elevations in Sichuan, Shaanxi, Hubei, Hunan and Guizhou provinces.The taxonomic status of the other allopatric

  11. Cholinergic Mesopontine Signals Govern Locomotion and Reward through Dissociable Midbrain Pathways.

    Science.gov (United States)

    Xiao, Cheng; Cho, Jounhong Ryan; Zhou, Chunyi; Treweek, Jennifer B; Chan, Ken; McKinney, Sheri L; Yang, Bin; Gradinaru, Viviana

    2016-04-20

    The mesopontine tegmentum, including the pedunculopontine and laterodorsal tegmental nuclei (PPN and LDT), provides major cholinergic inputs to midbrain and regulates locomotion and reward. To delineate the underlying projection-specific circuit mechanisms, we employed optogenetics to control mesopontine cholinergic neurons at somata and at divergent projections within distinct midbrain areas. Bidirectional manipulation of PPN cholinergic cell bodies exerted opposing effects on locomotor behavior and reinforcement learning. These motor and reward effects were separable via limiting photostimulation to PPN cholinergic terminals in the ventral substantia nigra pars compacta (vSNc) or to the ventral tegmental area (VTA), respectively. LDT cholinergic neurons also form connections with vSNc and VTA neurons; however, although photo-excitation of LDT cholinergic terminals in the VTA caused positive reinforcement, LDT-to-vSNc modulation did not alter locomotion or reward. Therefore, the selective targeting of projection-specific mesopontine cholinergic pathways may offer increased benefit in treating movement and addiction disorders.

  12. Huperzine A protects sepsis associated encephalopathy by promoting the deficient cholinergic nervous function.

    Science.gov (United States)

    Zhu, Sen-Zhi; Huang, Wei-Ping; Huang, Lin-Qiang; Han, Yong-Li; Han, Qian-Peng; Zhu, Gao-Feng; Wen, Miao-Yun; Deng, Yi-Yu; Zeng, Hong-Ke

    2016-09-19

    Neuroinflammatory deregulation in the brain plays a crucial role in the pathogenesis of sepsis associated encephalopathy (SAE). Given the mounting evidence of anti-inflammatory and neuroprotective effects of the cholinergic nervous system, it is surprising that there is little information about its changes in the brain during sepsis. To elucidate the role of the cholinergic nervous system in SAE, hippocampal choline acetyltransferase, muscarinic acetylcholine receptor-1, acetylcholinesterase and acetylcholine were evaluated in LPS-induced sepsis rats. Expression of pro-inflammatory cytokines, neuronal apoptosis, and animal cognitive performance were also assessed. Furthermore, therapeutic effects of the acetylcholinesterase inhibitor Huperzine A (HupA) on the hippocampal cholinergic nervous function and neuroinflammation were evaluated. A deficiency of the cholinergic nervous function was revealed in SAE, accompanied with over-expressed pro-inflammatory cytokines, increase in neuronal apoptosis and brain cognitive impairment. HupA remarkably promoted the deficient cholinergic nervous function and attenuated the abnormal neuroinflammation in SAE, paralleled with the recovery of brain function. We suggest that the deficiency of the cholinergic nervous function and the abnormal neuroinflammation are synergistically implicated in the pathogenesis of SAE. Thus, HupA is a potential therapeutic candidate for SAE, as it improves the deficient cholinergic nervous function and exerts anti-inflammatory action.

  13. Quaternary paleoceanography of the central Arctic based on Integrated Ocean Drilling Program Arctic Coring Expedition 302 foraminiferal assemblages

    Science.gov (United States)

    Cronin, T. M.; Smith, S.A.; Eynaud, F.; O'Regan, M.; King, J.

    2008-01-01

    The Integrated Ocean Drilling Program (IODP) Arctic Coring Expedition (ACEX) Hole 4C from the Lomonosov Ridge in the central Arctic Ocean recovered a continuous 18 in record of Quaternary foraminifera yielding evidence for seasonally ice-free interglacials during the Matuyama, progressive development of large glacials during the mid-Pleistocene transition (MPT) ???1.2-0.9 Ma, and the onset of high-amplitude 100-ka orbital cycles ???500 ka. Foraminiferal preservation in sediments from the Arctic is influenced by primary (sea ice, organic input, and other environmental conditions) and secondary factors (syndepositional, long-term pore water dissolution). Taking these into account, the ACEX 4C record shows distinct maxima in agglutinated foraminiferal abundance corresponding to several interglacials and deglacials between marine isotope stages (MIS) 13-37, and although less precise dating is available for older sediments, these trends appear to continue through the Matuyama. The MPT is characterized by nearly barren intervals during major glacials (MIS 12, 16, and 22-24) and faunal turnover (MIS 12-24). Abundant calcareous planktonic (mainly Neogloboquadrina pachyderma sin.) and benthic foraminifers occur mainly in interglacial intervals during the Brunhes and very rarely in the Matuyama. A distinct faunal transition from calcareous to agglutinated foraminifers 200-300 ka in ACEX 4C is comparable to that found in Arctic sediments from the Lomonosov, Alpha, and Northwind ridges and the Morris Jesup Rise. Down-core disappearance of calcareous taxa is probably related to either reduced sea ice cover prior to the last few 100-ka cycles, pore water dissolution, or both. Copyright 2008 by the American Geophysical Union.

  14. The involvement of cholinergic neurons in the spreading of tau pathology

    Directory of Open Access Journals (Sweden)

    Diana eSimon

    2013-06-01

    Full Text Available Long time ago, it was described the selective loss of cholinergic neurons during the development of Alzheimer disease. Recently, it has been suggested that tau protein may play a role in that loss of cholinergic neurons through a mechanism involving the interaction of extracellular tau with M1/M3 muscarinic receptors present in the cholinergic neurons. This interaction between tau and muscarinic receptors may be a way, although not the only one, to explain the spreading of tau pathology occurring in Alzheimer disease.

  15. Cholinergic denervation of the hippocampal formation does not produce long-term changes in glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Harrell, L.E.; Davis, J.N.

    1984-07-01

    Decreased glucose metabolism is found in Alzheimer's disease associated with a loss of cholinergic neurons. The relationship between the chronic cholinergic denervation produced by medial septal lesions and glucose metabolism was studied using 2-deoxy-D-(/sup 3/H)glucose in the rat hippocampal formation. Hippocampal glucose metabolism was increased 1 week after medial septal lesions. Three weeks after lesions, glucose metabolism was profoundly suppressed in all regions. By 3 months, intraregional hippocampal glucose metabolism had returned to control values. Our results demonstrate that chronic cholinergic denervation of the hippocampal formation does not result in permanent alterations of metabolic activity.

  16. Tolerance of nestin+ cholinergic neurons in the basal forebrain against colchicine-induced cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Jing Yu; Kaihua Guo; Dongpei Li; Jinhai Duan; Juntao Zou; Junhua Yang; Zhibin Yao

    2011-01-01

    In the present study we injected colchicine into the lateral ventricle of Sprague-Dawley rats to investigate the effects of colchicine on the number of different-type neurons in the basal forebrain and to search for neurons resistant to injury. After colchicine injection, the number of nestin+ cholinergic neurons was decreased at 1 day, but increased at 3 days and peaked at 14-28 days. The quantity of nestin- cholinergic neurons, parvalbumin-positive neurons and choline acetyl transferase-positive neurons decreased gradually. Our results indicate that nestin+ cholinergic neurons possess better tolerance to colchicine-induced neurotoxicity.

  17. Electroacupuncture at Zusanli (ST36 Prevents Intestinal Barrier and Remote Organ Dysfunction following Gut Ischemia through Activating the Cholinergic Anti-Inflammatory-Dependent Mechanism

    Directory of Open Access Journals (Sweden)

    Sen Hu

    2013-01-01

    Full Text Available This study investigated the protective effect and mechanism of electroacupuncture at ST36 points on the intestinal barrier dysfunction and remote organ injury after intestinal ischemia and reperfusion injury in rats. Rats were subjected to gut ischemia for 30 min, and then received electroacupuncture for 30 min with or without abdominal vagotomy or intraperitoneal administration of cholinergic α7 nicotinic acetylcholine receptor (α7nAChR inhibitor. Then we compared its effects with electroacupuncture at nonchannel points, vagal nerve stimulation, or intraperitoneal administration of cholinergic agonist. Cytokine levels in plasma and tissue of intestine, lung, and liver were assessed 60 min after reperfusion. Intestinal barrier injury was detected by histology, gut injury score, the permeability to 4 kDa FITC-dextran, and changes in tight junction protein ZO-1 using immunofluorescence and Western blot. Electroacupuncture significantly lowered the levels of tumor necrosis factor-α and interleukin-8 in plasma and organ tissues, decreased intestinal permeability to FITC-dextran, and prevented changes in ZO-1 protein expression and localization. However, abdominal vagotomy or intraperitoneal administration of cholinergic α7nAChR inhibitor reversed these effects of electroacupuncture. These findings suggest that electroacupuncture attenuates the systemic inflammatory response through protection of intestinal barrier integrity after intestinal ischemia injury in the presence of an intact vagus nerve.

  18. Cholinergic urethral brush cells are widespread throughout placental mammals.

    Science.gov (United States)

    Deckmann, Klaus; Krasteva-Christ, Gabriela; Rafiq, Amir; Herden, Christine; Wichmann, Judy; Knauf, Sascha; Nassenstein, Christina; Grevelding, Christoph G; Dorresteijn, Adriaan; Chubanov, Vladimir; Gudermann, Thomas; Bschleipfer, Thomas; Kummer, Wolfgang

    2015-11-01

    We previously identified a population of cholinergic epithelial cells in murine, human and rat urethrae that exhibits a structural marker of brush cells (villin) and expresses components of the canonical taste transduction signaling cascade (α-gustducin, phospholipase Cβ2 (PLCβ2), transient receptor potential cation channel melanostatin 5 (TRPM5)). These cells serve as sentinels, monitoring the chemical composition of the luminal content for potentially hazardous compounds such as bacteria, and initiate protective reflexes counteracting further ingression. In order to elucidate cross-species conservation of the urethral chemosensory pathway we investigated the occurrence and molecular make-up of urethral brush cells in placental mammals. We screened 11 additional species, at least one in each of the five mammalian taxonomic units primates, carnivora, perissodactyla, artiodactyla and rodentia, for immunohistochemical labeling of the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), villin, and taste cascade components (α-gustducin, PLCβ2, TRPM5). Corresponding to findings in previously investigated species, urethral epithelial cells with brush cell shape were immunolabeled in all 11 mammals. In 8 species, immunoreactivities against all marker proteins and ChAT were observed, and double-labeling immunofluorescence confirmed the cholinergic nature of villin-positive and chemosensory (TRPM5-positive) cells. In cat and horse, these cells were not labeled by the ChAT antiserum used in this study, and unspecific reactions of the secondary antiserum precluded conclusions about ChAT-expression in the bovine epithelium. These data indicate that urethral brush cells are widespread throughout the mammalian kingdom and evolved not later than about 64.5millionyears ago. PMID:26044348

  19. Cholinergic urethral brush cells are widespread throughout placental mammals.

    Science.gov (United States)

    Deckmann, Klaus; Krasteva-Christ, Gabriela; Rafiq, Amir; Herden, Christine; Wichmann, Judy; Knauf, Sascha; Nassenstein, Christina; Grevelding, Christoph G; Dorresteijn, Adriaan; Chubanov, Vladimir; Gudermann, Thomas; Bschleipfer, Thomas; Kummer, Wolfgang

    2015-11-01

    We previously identified a population of cholinergic epithelial cells in murine, human and rat urethrae that exhibits a structural marker of brush cells (villin) and expresses components of the canonical taste transduction signaling cascade (α-gustducin, phospholipase Cβ2 (PLCβ2), transient receptor potential cation channel melanostatin 5 (TRPM5)). These cells serve as sentinels, monitoring the chemical composition of the luminal content for potentially hazardous compounds such as bacteria, and initiate protective reflexes counteracting further ingression. In order to elucidate cross-species conservation of the urethral chemosensory pathway we investigated the occurrence and molecular make-up of urethral brush cells in placental mammals. We screened 11 additional species, at least one in each of the five mammalian taxonomic units primates, carnivora, perissodactyla, artiodactyla and rodentia, for immunohistochemical labeling of the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), villin, and taste cascade components (α-gustducin, PLCβ2, TRPM5). Corresponding to findings in previously investigated species, urethral epithelial cells with brush cell shape were immunolabeled in all 11 mammals. In 8 species, immunoreactivities against all marker proteins and ChAT were observed, and double-labeling immunofluorescence confirmed the cholinergic nature of villin-positive and chemosensory (TRPM5-positive) cells. In cat and horse, these cells were not labeled by the ChAT antiserum used in this study, and unspecific reactions of the secondary antiserum precluded conclusions about ChAT-expression in the bovine epithelium. These data indicate that urethral brush cells are widespread throughout the mammalian kingdom and evolved not later than about 64.5millionyears ago.

  20. Impact of basal forebrain cholinergic inputs on basolateral amygdala neurons.

    Science.gov (United States)

    Unal, Cagri T; Pare, Denis; Zaborszky, Laszlo

    2015-01-14

    In addition to innervating the cerebral cortex, basal forebrain cholinergic (BFc) neurons send a dense projection to the basolateral nucleus of the amygdala (BLA). In this study, we investigated the effect of near physiological acetylcholine release on BLA neurons using optogenetic tools and in vitro patch-clamp recordings. Adult transgenic mice expressing cre-recombinase under the choline acetyltransferase promoter were used to selectively transduce BFc neurons with channelrhodopsin-2 and a reporter through the injection of an adeno-associated virus. Light-induced stimulation of BFc axons produced different effects depending on the BLA cell type. In late-firing interneurons, BFc inputs elicited fast nicotinic EPSPs. In contrast, no response could be detected in fast-spiking interneurons. In principal BLA neurons, two different effects were elicited depending on their activity level. When principal BLA neurons were quiescent or made to fire at low rates by depolarizing current injection, light-induced activation of BFc axons elicited muscarinic IPSPs. In contrast, with stronger depolarizing currents, eliciting firing above ∼ 6-8 Hz, these muscarinic IPSPs lost their efficacy because stimulation of BFc inputs prolonged current-evoked afterdepolarizations. All the effects observed in principal neurons were dependent on muscarinic receptors type 1, engaging different intracellular mechanisms in a state-dependent manner. Overall, our results suggest that acetylcholine enhances the signal-to-noise ratio in principal BLA neurons. Moreover, the cholinergic engagement of afterdepolarizations may contribute to the formation of stimulus associations during fear-conditioning tasks where the timing of conditioned and unconditioned stimuli is not optimal for the induction of synaptic plasticity.

  1. Effects of cholinergic and noradrenergic agents on locomotion in the mudpuppy (Necturus maculatus).

    Science.gov (United States)

    Fok, M; Stein, R B

    2002-08-01

    Some neurotransmitters act consistently on the central pattern generator (CPG) for locomotion in a wide range of vertebrates. In contrast, acetylcholine (ACh) and noradrenaline (NA) have various effects on locomotion in different preparations. The roles of ACh and NA have not been studied in amphibian walking, so we examined their effects in an isolated spinal cord preparation of the mudpuppy ( Necturus maculatus). This preparation contains a CPG that produces locomotor activity when N-methyl- D-aspartic acid (NMDA), an excitatory amino acid agonist, is added to the bath. The addition of carbachol, a long acting ACh agonist, to the bath disrupted the walking rhythm induced by NMDA, while not changing the level of activity in flexor and extensor motoneurons. Adding clonidine, an alpha(2)-noradrenergic agonist, had no effect on the NMDA-induced walking rhythm. Physostigmine, an ACh-esterase inhibitor, disrupted the walking rhythm, presumably by potentiating the effects of endogenously released ACh. Atropine, an ACh antagonist that binds to muscarinic ACh receptors, blocked the effects of carbachol, indicating that the action is mediated, at least in part, by muscarinic receptors. In the absence of carbachol, atropine had no effect. Locomotion was not induced by carbachol, atropine or clonidine in a resting spinal cord preparation. Cholinergic actions do not seem to be essential to the CPG for walking in the mudpuppy, but ACh may convert a rhythmic walking state to a more tonic state with occasional bursts of EMG activity for postural adjustments.

  2. The Role of Gut Microflora and the Cholinergic Anti-inflammatory Neuroendocrine System in Diabetes Mellitus

    Science.gov (United States)

    Parekh, Parth J.; Nayi, Vipul R.; Johnson, David A.; Vinik, Aaron I.

    2016-01-01

    The obesity epidemic has drastically impacted the state of health care in the United States. Paralleling this epidemic is the incidence of diabetes mellitus, with a notable shift toward a much younger age of onset. While central to the pathogenesis of diabetes associated with obesity is the role of inflammation attributed to “adiposopathy.” Emerging data suggest that changes in sympathetic/parasympathetic balance regulated by the brain precede changes in the inflammatory cascade. It has now been established that the gut microflora contributes significantly to the activation and inhibition of autonomic control and impact the set of the neuroinflammatory inhibitory reflex mediated by the cholinergic nervous system. There has been a paradigm shift toward further investigating commensal bacteria in the pathogenesis of obesity and diabetes mellitus and its complications, as dysbiosis is thought to play a pivotal role in diabetic-associated disorders. This paper is intended to evaluate the role of intestinal dysbiosis in the pathogenesis of diabetes mellitus and examine the potential for restoration of balance via use of probiotics.

  3. The Role of Gut Microflora and the Cholinergic Anti-inflammatory Neuroendocrine System in Diabetes Mellitus

    Science.gov (United States)

    Parekh, Parth J.; Nayi, Vipul R.; Johnson, David A.; Vinik, Aaron I.

    2016-01-01

    The obesity epidemic has drastically impacted the state of health care in the United States. Paralleling this epidemic is the incidence of diabetes mellitus, with a notable shift toward a much younger age of onset. While central to the pathogenesis of diabetes associated with obesity is the role of inflammation attributed to “adiposopathy.” Emerging data suggest that changes in sympathetic/parasympathetic balance regulated by the brain precede changes in the inflammatory cascade. It has now been established that the gut microflora contributes significantly to the activation and inhibition of autonomic control and impact the set of the neuroinflammatory inhibitory reflex mediated by the cholinergic nervous system. There has been a paradigm shift toward further investigating commensal bacteria in the pathogenesis of obesity and diabetes mellitus and its complications, as dysbiosis is thought to play a pivotal role in diabetic-associated disorders. This paper is intended to evaluate the role of intestinal dysbiosis in the pathogenesis of diabetes mellitus and examine the potential for restoration of balance via use of probiotics. PMID:27375553

  4. The Role of Gut Microflora and the Cholinergic Anti-inflammatory Neuroendocrine System in Diabetes Mellitus.

    Science.gov (United States)

    Parekh, Parth J; Nayi, Vipul R; Johnson, David A; Vinik, Aaron I

    2016-01-01

    The obesity epidemic has drastically impacted the state of health care in the United States. Paralleling this epidemic is the incidence of diabetes mellitus, with a notable shift toward a much younger age of onset. While central to the pathogenesis of diabetes associated with obesity is the role of inflammation attributed to "adiposopathy." Emerging data suggest that changes in sympathetic/parasympathetic balance regulated by the brain precede changes in the inflammatory cascade. It has now been established that the gut microflora contributes significantly to the activation and inhibition of autonomic control and impact the set of the neuroinflammatory inhibitory reflex mediated by the cholinergic nervous system. There has been a paradigm shift toward further investigating commensal bacteria in the pathogenesis of obesity and diabetes mellitus and its complications, as dysbiosis is thought to play a pivotal role in diabetic-associated disorders. This paper is intended to evaluate the role of intestinal dysbiosis in the pathogenesis of diabetes mellitus and examine the potential for restoration of balance via use of probiotics. PMID:27375553

  5. Ecosystem disturbances in Central European spruce forests: a multi-proxy integration of dendroecology and sedimentary records

    Science.gov (United States)

    Clear, Jennifer; Chiverrell, Richard; Kunes, Petr; Svoboda, Miroslav; Boyle, John

    2016-04-01

    Disturbance dynamics in forest ecosystems shows signs of perturbation in the light of changing climate regimes with the frequency and intensity of events (e.g. pathogens in North America and Central Europe) amplified, becoming more frequent and severe. The montane Norway spruce (Picea abies) dominated forests of Central Europe are a niche habitat and environment; situated outside their natural boreal distribution (e.g. Fenno-Scandinavia). These communities are at or near their ecological limits and are vulnerable to both short term disturbances (e.g. fire, windstorm and pathogens) and longer-term environmental change (e.g. climate induced stress and changing disturbance patterns). Researches have linked negative impacts on spruce forest with both wind disturbance (wind-throw) and outbreaks of spruce bark beetle (Ips typographus), and there is growing evidence for co-association with wind damage enhancing pathogenic outbreaks. Examples include: in the Bohemian Forest (Czech Republic) the mid-1990s spruce bark beetle outbreak and the 2007 windstorm and subsequent bark beetle outbreak. In the High Tatra Mountains (Slovakia) there is a further co-association of forest disturbance with windstorms (2004 and 2014) and an ongoing bark beetle outbreak. The scale and severity of these recent outbreaks of spruce bark beetle are unprecedented in the historical forest records. Here, findings from ongoing research developing and integrating data from dendroecological, sedimentary palaeoecological and geochemical time series to develop a longer-term perspective on forest dynamics in these regions. Tree-ring series from plots or forest stands (>500) are used alongside lake (5) and forest hollow (3) sediments from the Czech and Slovak Republics to explore the local, regional and biogeographical scale of forest disturbances. Dendroecological data showing tree-ring gap recruitment and post-suppression growth release highlight frequent disturbance events focused on tree or forest

  6. Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys

    Science.gov (United States)

    Turchi, Janita; Saunders, Richard C.; Mishkin, Mortimer

    2005-01-01

    Excitotoxic lesion studies have confirmed that the rhinal cortex is essential for visual recognition ability in monkeys. To evaluate the mnemonic role of cholinergic inputs to this cortical region, we compared the visual recognition performance of monkeys given rhinal cortex infusions of a selective cholinergic immunotoxin, ME20.4-SAP, with the performance of monkeys given control infusions into this same tissue. The immunotoxin, which leads to selective cholinergic deafferentation of the infused cortex, yielded recognition deficits of the same magnitude as those produced by excitotoxic lesions of this region, providing the most direct demonstration to date that cholinergic activation of the rhinal cortex is essential for storing the representations of new visual stimuli and thereby enabling their later recognition. PMID:15684066

  7. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons

    Science.gov (United States)

    Wurtman, R. J.

    1992-01-01

    The unique propensity of cholinergic neurons to use choline for two purposes--ACh and membrane phosphatidylcholine synthesis--may contribute to their selective vulnerability in Alzheimer's disease and other cholinergic neurodegenerative disorders. When physiologically active, the neurons use free choline taken from the 'reservoir' in membrane phosphatidylcholine to synthesize ACh; this can lead to an actual decrease in the quantity of membrane per cell. Alzheimer's disease (but not Down's syndrome, or other neurodegenerative disorders) is associated with characteristic neurochemical lesions involving choline and ethanolamine: brain levels of these compounds are diminished, while those of glycerophosphocholine and glycerophosphoethanolamine (breakdown products of their respective membrane phosphatides) are increased, both in cholinergic and noncholinergic brain regions. Perhaps this metabolic disturbance and the tendency of cholinergic neurons to 'export' choline--in the form of ACh--underlie the selective vulnerability of the neurons. Resulting changes in membrane composition could abnormally expose intramembraneous proteins such as amyloid precursor protein to proteases.

  8. Outcome of Patients with Cholinergic Insecticide Poisoning Treated with Gastric Lavage: A Prospective Observational Cohort Study

    Directory of Open Access Journals (Sweden)

    Mekkattukunnel Andrews

    2014-12-01

    Conclusion: Number or timing of GL does not show any association with mortality while multiple GL had protective effect against development of late RF and IMS. Hence, GL might be beneficial in cholinergic insecticide poisoning.

  9. Transplantation of cholinergic neural stem cells in a mouse model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    WANG Qing-hua; XU Ru-xiang; Seigo Nagao

    2005-01-01

    @@ It is believed that the degeneration of cholinergic cells in the nucleus basalis of Meynert (NBM) and the loss of cortical cholinergic innervation cause dementia of Alzheimer's disease (AD).1 Currently available therapeutic interventions are mainly aimed at alleviating the cholinergic deficits. Unfortunately, these strategies do not prevent the disease, but instead offer limited symptomatic improvement.2 A recent study demonstrated that transplantation of in vitro expanded neural stem cells (NSCs) in an animal model of Parkinson's disease (PD) resulted in functional recovery of the animals to some extent,2 suggesting that such neural precursors might offer a useful future therapy for AD. In this study, we tried to find whether mouse embryonic stem (ES) cell derived cholinergic NSCs grafted in the prefrontal and parietal cortex have effects on the disruption of spatial memory following development of lesion in NBM.

  10. Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep.

    Science.gov (United States)

    Van Dort, Christa J; Zachs, Daniel P; Kenny, Jonathan D; Zheng, Shu; Goldblum, Rebecca R; Gelwan, Noah A; Ramos, Daniel M; Nolan, Michael A; Wang, Karen; Weng, Feng-Ju; Lin, Yingxi; Wilson, Matthew A; Brown, Emery N

    2015-01-13

    Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep.

  11. Integration

    DEFF Research Database (Denmark)

    Emerek, Ruth

    2004-01-01

    Bidraget diskuterer de forskellige intergrationsopfattelse i Danmark - og hvad der kan forstås ved vellykket integration......Bidraget diskuterer de forskellige intergrationsopfattelse i Danmark - og hvad der kan forstås ved vellykket integration...

  12. Integrated assessment of a new Waste-to-Energy facility in Central Greece in the context of regional perspectives.

    Science.gov (United States)

    Perkoulidis, G; Papageorgiou, A; Karagiannidis, A; Kalogirou, S

    2010-07-01

    The main aim of this study is the integrated assessment of a proposed Waste-to-Energy facility that could contribute in the Municipal Solid Waste Management system of the Region of Central Greece. In the context of this paper alternative transfer schemes for supplying the candidate facility were assessed considering local conditions and economical criteria. A mixed-integer linear programming model was applied for the determination of optimum locations of Transfer Stations for an efficient supplying chain between the waste producers and the Waste-to-Energy facility. Moreover different Regional Waste Management Scenarios were assessed against multiple criteria, via the Multi Criteria Decision Making method ELECTRE III. The chosen criteria were total cost, Biodegradable Municipal Waste diversion from landfill, energy recovery and Greenhouse Gas emissions and the analysis demonstrated that a Waste Management Scenario based on a Waste-to-Energy plant with an adjacent landfill for disposal of the residues would be the best performing option for the Region, depending however on the priorities of the decision makers. In addition the study demonstrated that efficient planning is necessary and the case of three sanitary landfills operating in parallel with the WtE plant in the study area should be avoided. Moreover alternative cases of energy recovery of the candidate Waste-to-Energy facility were evaluated against the requirements of the new European Commission Directive on waste in order for the facility to be recognized as recovery operation. The latter issue is of high significance and the decision makers in European Union countries should take it into account from now on, in order to plan and implement facilities that recover energy efficiently. Finally a sensitivity check was performed in order to evaluate the effects of increased recycling rate, on the calorific value of treated Municipal Solid Waste and the gate fee of the candidate plant and found that increased

  13. Integrated assessment of a new Waste-to-Energy facility in Central Greece in the context of regional perspectives

    International Nuclear Information System (INIS)

    The main aim of this study is the integrated assessment of a proposed Waste-to-Energy facility that could contribute in the Municipal Solid Waste Management system of the Region of Central Greece. In the context of this paper alternative transfer schemes for supplying the candidate facility were assessed considering local conditions and economical criteria. A mixed-integer linear programming model was applied for the determination of optimum locations of Transfer Stations for an efficient supplying chain between the waste producers and the Waste-to-Energy facility. Moreover different Regional Waste Management Scenarios were assessed against multiple criteria, via the Multi Criteria Decision Making method ELECTRE III. The chosen criteria were total cost, Biodegradable Municipal Waste diversion from landfill, energy recovery and Greenhouse Gas emissions and the analysis demonstrated that a Waste Management Scenario based on a Waste-to-Energy plant with an adjacent landfill for disposal of the residues would be the best performing option for the Region, depending however on the priorities of the decision makers. In addition the study demonstrated that efficient planning is necessary and the case of three sanitary landfills operating in parallel with the WtE plant in the study area should be avoided. Moreover alternative cases of energy recovery of the candidate Waste-to-Energy facility were evaluated against the requirements of the new European Commission Directive on waste in order for the facility to be recognized as recovery operation. The latter issue is of high significance and the decision makers in European Union countries should take it into account from now on, in order to plan and implement facilities that recover energy efficiently. Finally a sensitivity check was performed in order to evaluate the effects of increased recycling rate, on the calorific value of treated Municipal Solid Waste and the gate fee of the candidate plant and found that increased

  14. Neuroinflammation not associated with cholinergic degeneration in aged-impaired brain

    OpenAIRE

    McQuail, Joseph A.; Riddle, David R.; Nicolle, Michelle M.

    2010-01-01

    Degeneration of the cholinergic neurons in the basal forebrain and elevation of inflammatory markers are well-established hallmarks of Alzheimer's disease; however, the interplay of these processes in normal aging is not extensively studied. Consequently, we conducted a neuroanatomical investigation to quantify cholinergic neurons and activated microglia in the medial septum/vertical diagonal band (MS/VDB) of young (6 months) and aged (28 months) Fisher 344 × Brown Norway F1 rats. Aged rats i...

  15. Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene

    OpenAIRE

    Kratsios, Paschalis; Stolfi, Alberto; Levine, Michael; Hobert, Oliver

    2011-01-01

    Cholinergic motor neurons are defined by the co-expression of a battery of genes which encode proteins that act sequentially to synthesize, package and degrade acetylcholine and reuptake its breakdown product, choline. How expression of these critical motor neuron identity determinants is controlled and coordinated is not understood. We show here that in the nematode Caenorhabditis elegans all members of the cholinergic gene battery, as well as many other markers of terminal motor neuron fate...

  16. Cholinergic axon length reduced by 300 meters in the brain of an Alzheimer mouse model

    DEFF Research Database (Denmark)

    Nikolajsen, Gitte; Jensen, Morten Skovgaard; West, Mark J.

    2011-01-01

    Modern stereological techniques have been used to show that the total length of the cholinergic fibers in the cerebral cortex of the APPswe/PS1deltaE9 mouse is reduced by almost 300 meters at 18 months of age and has a nonlinear relationship to the amount of transgenetically-induced amyloidosis. ....... These data provide rigorous quantitative morphological evidence that Alzheimer's-like amyloidosis affects the axons of the cholinergic enervation of the cerebral cortex....

  17. Ultrastructural localization of cholinergic muscarinic receptors in rat brain cortical capillaries

    OpenAIRE

    Luiten, PGM; DEJONG, GI; VANDERZEE, EA; vanDijken, H; van Dijken, H.

    1996-01-01

    Cholinergic innervation of the cerebrovasculature is known to regulate vascular tone, perfusion rate and permeability of the microvascular wall. Notably the cholinergic innervation of cerebral capillaries is of interest since these capillaries form the blood-brain barrier. Although there is a general consensus as to the presence of nicotinic and muscarinic receptors in the domain of the capillary wall, their precise anatomical position is unknown. The subcellular localization of muscarinic re...

  18. EEG sleep and the cholinergic REM induction test in anorexic and bulimic patients

    OpenAIRE

    Lauer, C.; Zulley, Jürgen; Krieg, J. C.; Riemann, D.; Berger , M.

    1988-01-01

    The electroencephalographic (EEG) sleep of 20 anorexic patients, 10 bulimic patients, and 10 age-matched healthy controls was studied. In addition, six anorexic patients and six bulimic patients had a cholinergic rapid eye movement (REM) sleep induction test (RIT) performed with the cholinergic agent RS 86. The three samples showed no major differences in sleep patterns. The same held true when attention was focused on patients who additionally met DSM-III criteria for major depression. The R...

  19. Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats.

    Science.gov (United States)

    Ferencz, I; Leanza, G; Nanobashvili, A; Kokaia, M; Lindvall, O

    2000-06-01

    Intraventricular administration of the immunotoxin 192 IgG-saporin in rats has been shown to cause a selective loss of cholinergic afferents to the hippocampus and cortical areas, and to facilitate seizure development in hippocampal kindling. Here we demonstrate that this lesion also accelerates seizure progression when kindling is induced by electrical stimulations in the amygdala. However, whereas intraventricular 192 IgG-saporin facilitated the development of the initial stages of hippocampal kindling, the same lesion promoted the late stages of amygdala kindling. To explore the role of various parts of the basal forebrain cholinergic system in amygdala kindling, selective lesions of the cholinergic projections to either hippocampus or cortex were produced by intraparenchymal injections of 192 IgG-saporin into medial septum/vertical limb of the diagonal band or nucleus basalis, respectively. Cholinergic denervation of the cortical regions caused acceleration of amygdala kindling closely resembling that observed after the more widespread lesion induced by intraventricular 192 IgG-saporin. In contrast, removal of the cholinergic input to the hippocampus had no effect on the development of amygdala kindling. These data indicate that basal forebrain cholinergic neurons suppress kindling elicited from amygdala, and that this dampening effect is mediated via cortical but not hippocampal projections.

  20. Cholinergic Depletion in Alzheimer’s Disease Shown by [18F]FEOBV Autoradiography

    Directory of Open Access Journals (Sweden)

    Maxime J. Parent

    2013-01-01

    Full Text Available Rationale. Alzheimer’s Disease (AD is a neurodegenerative condition characterized in part by deficits in cholinergic basalocortical and septohippocampal pathways. [18F]Fluoroethoxybenzovesamicol ([18F]FEOBV, a Positron Emission Tomography ligand for the vesicular acetylcholine transporter (VAChT, is a potential molecular agent to investigate brain diseases associated with presynaptic cholinergic losses. Purpose. To demonstrate this potential, we carried out an [18F]FEOBV autoradiography study to compare postmortem brain tissues from AD patients to those of age-matched controls. Methods. [18F]FEOBV autoradiography binding, defined as the ratio between regional grey and white matter, was estimated in the hippocampus (13 controls, 8 AD and prefrontal cortex (13 controls, 11 AD. Results. [18F]FEOBV binding was decreased by 33% in prefrontal cortex, 25% in CA3, and 20% in CA1. No changes were detected in the dentate gyrus of the hippocampus, possibly because of sprouting or upregulation toward the resilient glutamatergic neurons of the dentate gyrus. Conclusion. This is the first demonstration of [18F]FEOBV focal binding changes in cholinergic projections to the cortex and hippocampus in AD. Such cholinergic synaptic (and more specifically VAChT alterations, in line with the selective basalocortical and septohippocampal cholinergic losses documented in AD, indicate that [18F]FEOBV is indeed a promising ligand to explore cholinergic abnormalities in vivo.

  1. Impairment of reward-related learning by cholinergic cell ablation in the striatum.

    Science.gov (United States)

    Kitabatake, Yasuji; Hikida, Takatoshi; Watanabe, Dai; Pastan, Ira; Nakanishi, Shigetada

    2003-06-24

    The striatum in the basal ganglia-thalamocortical circuitry is a key neural substrate that is implicated in motor balance and procedural learning. The projection neurons in the striatum are dynamically modulated by nigrostriatal dopaminergic input and intrastriatal cholinergic input. The role of intrastriatal acetylcholine (ACh) in learning behaviors, however, remains to be fully clarified. In this investigation, we examine the involvement of intrastriatal ACh in different categories of learning by selectively ablating the striatal cholinergic neurons with use of immunotoxin-mediated cell targeting. We show that selective ablation of cholinergic neurons in the striatum impairs procedural learning in the tone-cued T-maze memory task. Spatial delayed alternation in the T-maze learning test is also impaired by cholinergic cell elimination. In contrast, the deficit in striatal ACh transmission has no effect on motor learning in the rota-rod test or spatial learning in the Morris water-maze test or on contextual- and tone-cued conditioning fear responses. We also report that cholinergic cell elimination adaptively up-regulates nicotinic ACh receptors not only within the striatum but also in the cerebral cortex and substantia nigra. The present investigation indicates that cholinergic modulation in the local striatal circuit plays a pivotal role in regulation of neural circuitry involving reward-related procedural learning and working memory. PMID:12802017

  2. Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction

    DEFF Research Database (Denmark)

    Christensen, Mark Holm; Ishibashi, Masaru; Nielsen, Michael Linnemann;

    2014-01-01

    The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved...... intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15–P34). Nicotine increased neuronal firing of cholinergic cells...

  3. Acetylcholinesterase in central vocal control nuclei of the zebra finch (Taeniopygia guttata)

    Indian Academy of Sciences (India)

    Monika Sadananda

    2004-06-01

    The distribution of acetylcholinesterase (AChE) in the central vocal control nuclei of the zebra finch was studied using enzyme histochemistry. AChE fibres and cells are intensely labelled in the forebrain nucleus area X, strongly labelled in high vocal centre (HVC) perikarya, and moderately to lightly labelled in the somata and neuropil of vocal control nuclei robust nucleus of arcopallium (RA), medial magnocellular nucleus of the anterior nidopallium (MMAN) and lateral magnocellular nucleus of the anterior nidopallium (LMAN). The identified sites of cholinergic and/or cholinoceptive neurons are similar to the cholinergic presence in vocal control regions of other songbirds such as the song sparrow, starling and another genus of the zebra finch (Poephila guttata), and to a certain extent in parallel vocal control regions in vocalizing birds such as the budgerigar. AChE presence in the vocal control system suggests innervation by either afferent projecting cholinergic systems and/or local circuit cholinergic neurons. Co-occurrence with choline acetyltransferase (ChAT) indicates efferent cholinergic projections. The cholinergic presence in parts of the zebra finch vocal control system, such as the area X, that is also intricately wired with parts of the basal ganglia, the descending fibre tracts and brain stem nuclei could underlie this circuitry’s involvement in sensory processing and motor control of song.

  4. Neurogenic abnormalities in Alzheimer's disease differ between stages of neurogenesis and are partly related to cholinergic pathology.

    Science.gov (United States)

    Perry, Elaine K; Johnson, Mary; Ekonomou, Antigoni; Perry, Robert H; Ballard, Clive; Attems, Johannes

    2012-08-01

    Neurogenesis occurs in the subventricular zone and the sub-granular layer of the hippocampus and is thought to take place in 5 stages, including proliferation, differentiation, migration, targeting, and integration phases, respectively. In Alzheimer's disease (AD) both increased and decreased neurogenesis has been reported and cholinergic activity is assumed to be involved in neurogenesis. The aim of this study was to systematically assess different phases of neurogenesis and their relation to AD and cholinergic pathology. We investigated post-mortem brain tissue from 20 AD patients and 21 non-demented controls that was neuropathologically characterized according to standardized criteria. Hippocampal sections were stained with antibodies against neurogenic markers Musashi-1, nestin, PSA-NCAM, doublecortin, and β-III-tubulin as well as ChAT (choline-acetyltransferase). Using image analysis immunoreactivity was assessed in the subventricular zone, the sub-granular layer, and the granule cell layer by determining the integrated optical density. In the sub-granular layer and the granule cell layer Musashi-1 and ChAT immunoreactivities were significantly lower in AD and decreased with increasing Braak stages. Conversely, immunorreactivities of both nestin and PSA-NCAM were significantly higher in AD and increased with increasing Braak stages while no changes were seen for doublecortin and β-III-tubulin, except for significantly higher doublecortin levels in the granule cell layer of AD cases. Of note, Musashi-1 immunoreactivity significantly correlated with ChAT immuonoreactivity across different Braak stages. In the subventricular zone only nestin immunoreactivity was significantly higher in AD and significantly increased with increasing Braak stages, while no significant differences were seen for all other markers. Our finding of a reduction of ChAT and Musashi-1 levels in AD is compatible with the assumption that cholinergic pathology per se has a detrimental

  5. Integrating ecosystem services analysis into scenario planning practice: accounting for street tree benefits with i-Tree valuation in Central Texas.

    Science.gov (United States)

    Hilde, Thomas; Paterson, Robert

    2014-12-15

    Scenario planning continues to gain momentum in the United States as an effective process for building consensus on long-range community plans and creating regional visions for the future. However, efforts to integrate more sophisticated information into the analytical framework to help identify important ecosystem services have lagged in practice. This is problematic because understanding the tradeoffs of land consumption patterns on ecological integrity is central to mitigating the environmental degradation caused by land use change and new development. In this paper we describe how an ecosystem services valuation model, i-Tree, was integrated into a mainstream scenario planning software tool, Envision Tomorrow, to assess the benefits of public street trees for alternative future development scenarios. The tool is then applied to development scenarios from the City of Hutto, TX, a Central Texas Sustainable Places Project demonstration community. The integrated tool represents a methodological improvement for scenario planning practice, offers a way to incorporate ecosystem services analysis into mainstream planning processes, and serves as an example of how open source software tools can expand the range of issues available for community and regional planning consideration, even in cases where community resources are limited. The tool also offers room for future improvements; feasible options include canopy analysis of various future land use typologies, as well as a generalized street tree model for broader U.S. application.

  6. Edible oil crops and their integration with the major cereals in North Shewa and South Welo, Central Highlands of Ethiopia: an ethnobotanical perspective.

    Science.gov (United States)

    Geleta, Mulatu; Asfaw, Zemede; Bekele, Endashaw; Teshome, Awegechew

    2002-01-01

    A total of 1050 sorghum (Sorghum bicolor) and tef (Eragrostis tef) fields distributed in six study sites within north Shewa and south Welo (Central Highlands of Ethiopia) were systematically surveyed to examine the status of integration of edible oil crops into the cereal-based farming system. Farmers' criteria for, and perception on, integration between edible oil crops and the major cereals at field level as well as integration between the cereal grains and the oilseeds in food making at home were studied and analyzed based on formal semi-structured interview and informal discussion with local expert farmers as key informants. Farmers' traditional space optimization technique has been instrumental in rightly fitting edible oil crops (as intercrops and border crops) into the cereal-based system. Six species of edible oil crops are integrated (70.3%) in various proportions in fields of sorghum and tef. At least one oil crop was significantly intercropped and/or border cropped in sorghum fields. Noog (Guizotia abyssinica) and sesame (Sesamum indicum) were the most important edible oil crops of the study area having strong integration with sorghum both at field and home level. On average, noog was more frequently intercropped with sorghum (8.3%) than with tef (4.5%), while it was more frequently border cropped with tef (32.4%) than with sorghum (19%). Sorghum was more frequently inter/border cropped with sesame (39/2%) than with tef (10.1/0.5%). The stronger the integration of a given oilseed with sorghum-based foods, the higher the companionship between sorghum fields and the oil crop in the landscape. This cultural practice by farmers has positive contributions to on-farm conservation of oil crops along with tef and specific sorghum landraces. The central theme of this paper therefore converges on the issue of on-farm in-situ agrobiodiversity conservation that was shaped by successive ancestral generations and passed on to the present.

  7. Cholinergic modulation of cognitive processing: insights drawn from computational models

    Directory of Open Access Journals (Sweden)

    Ehren L Newman

    2012-06-01

    Full Text Available Acetylcholine plays an important role in cognitive function, as shown by pharmacological manipulations that impact working memory, attention, episodic memory and spatial memory function. Acetylcholine also shows striking modulatory influences on the cellular physiology of hippocampal and cortical neurons. Modeling of neural circuits provides a framework for understanding how the cognitive functions may arise from the influence of acetylcholine on neural and network dynamics. We review the influences of cholinergic manipulations on behavioral performance in working memory, attention, episodic memory and spatial memory tasks, the physiological effects of acetylcholine on neural and circuit dynamics, and the computational models that provide insight into the functional relationships between the physiology and behavior. Specifically, we discuss the important role of acetylcholine in governing mechanisms of active maintenance in working memory tasks and in regulating network dynamics important for effective processing of stimuli in attention and episodic memory tasks. We also propose that theta rhythm play a crucial role as an intermediary between the physiological influences of acetylcholine and behavior in episodic and spatial memory tasks. We conclude with a synthesis of the existing modeling work and highlight future directions that are likely to be rewarding given the existing state of the literature for both empiricists and modelers.

  8. Neuroligin 2 is expressed in synapses established by cholinergic cells in the mouse brain.

    Directory of Open Access Journals (Sweden)

    Virág T Takács

    Full Text Available Neuroligin 2 is a postsynaptic protein that plays a critical role in the maturation and proper function of GABAergic synapses. Previous studies demonstrated that deletion of neuroligin 2 impaired GABAergic synaptic transmission, whereas its overexpression caused increased inhibition, which suggest that its presence strongly influences synaptic function. Interestingly, the overexpressing transgenic mouse line showed increased anxiety-like behavior and other behavioral phenotypes, not easily explained by an otherwise strengthened GABAergic transmission. This suggested that other, non-GABAergic synapses may also express neuroligin 2. Here, we tested the presence of neuroligin 2 at synapses established by cholinergic neurons in the mouse brain using serial electron microscopic sections double labeled for neuroligin 2 and choline acetyltransferase. We found that besides GABAergic synapses, neuroligin 2 is also present in the postsynaptic membrane of cholinergic synapses in all investigated brain areas (including dorsal hippocampus, somatosensory and medial prefrontal cortices, caudate putamen, basolateral amygdala, centrolateral thalamic nucleus, medial septum, vertical- and horizontal limbs of the diagonal band of Broca, substantia innominata and ventral pallidum. In the hippocampus, the density of neuroligin 2 labeling was similar in GABAergic and cholinergic synapses. Moreover, several cholinergic contact sites that were strongly labeled with neuroligin 2 did not resemble typical synapses, suggesting that cholinergic axons form more synaptic connections than it was recognized previously. We showed that cholinergic cells themselves also express neuroligin 2 in a subset of their input synapses. These data indicate that mutations in human neuroligin 2 gene and genetic manipulations of neuroligin 2 levels in rodents will potentially cause alterations in the cholinergic system as well, which may also have a profound effect on the functional properties

  9. Strategic integration of public transport networks with airport infrastructure in the megalopolis of Central Mexico: Evolution and challenges

    NARCIS (Netherlands)

    Salinas, C.R.; Garcia Cejudo, D.; Van Timmeren, A.

    2014-01-01

    Airports represent the contemporary global gateways of metropolitan areas worldwide. In the case of the megalopolis of Central Mexico, air transport was traditionally used only by upper social segments of the population, however, during the last years, the introduction of low-cost airlines in the co

  10. The central nervous system of ascidian larvae.

    Science.gov (United States)

    Hudson, Clare

    2016-09-01

    Ascidians are marine invertebrate chordates. Their tadpole larvae contain a dorsal tubular nervous system, resulting from the rolling up of a neural plate. Along the anterior-posterior (A-P) axis, the central nervous system (CNS) is organized into a sensory vesicle, neck, trunk ganglion, and tail nerve cord and consists of approximately only 330 cells, of which around 100 are thought to be neurons. The organization of distinct neuronal cell types and neurotransmitter gene expression within the CNS has been described. The unique developmental mode of ascidians, with a small number of cells and a fixed cell division pattern, allows individual cells to be traced throughout development. This feature has led to the complete documentation of the cell lineages of certain cell types in the CNS. Thus, a step-by-step understanding of nervous system development from the initial stages of neural induction to the neurogenesis of individual neurons is a feasible goal. The genetic control of neural fate induction and early neural plate patterning are now well understood. The molecular mechanisms specifying the cholinergic neurons of the trunk ganglion as well as the pigment cells of the sensory organs are also well elucidated. In addition, studies have begun on the morphogenetic processes of neurulation. Remaining challenges include building an embryonic atlas integrating gene expression patterns, cell lineage, and neuronal cell types as well as developing the gene regulatory networks of cell fate specification and integrating them with the genetic control of morphogenesis. WIREs Dev Biol 2016, 5:538-561. doi: 10.1002/wdev.239 For further resources related to this article, please visit the WIREs website. PMID:27328318

  11. Crinum zeylanicum memory enhancing effect is mediated via central cholinergic transmission system

    Directory of Open Access Journals (Sweden)

    Tijani Adeniyi Yahaya

    2015-10-01

    Conclusion: The extract, as well as its partially purified alkaloid, possesses potential that may be employed for therapeutic management of Alzheimer's disease. [Int J Basic Clin Pharmacol 2015; 4(5.000: 864-868

  12. An increase in intracelluar free calcium ions modulated by cholinergic receptors in rat facial nucleus

    Institute of Scientific and Technical Information of China (English)

    SUN Da-wei; ZHOU Rui; LI Na; ZHANG Qiu-gui; ZHU Fu-gao

    2009-01-01

    Background Ca2+in the central nervous system plays important roles in brain physiology, including neuronal survival and regeneration in rats with injured facial motoneurons. The present research was to study the modulations of intracellular free Ca2+ concentrations by cholinergic receptors in rat facial nucleus, and the mechanisms of the modulations. Methods The fluorescence intensity of facial nucleus in Fluo-3 AM loaded acute brainstem slices was detected by applying intracellular free Ca2+ measurement technique via confocal laser scanning microscope. The changes of fluorescence intensity of facial nucleus indicate the average changes of intracellular free Ca2+ levels of the neurons. Results Acetylcholine was effective at increasing the fluorescence intensity of facial nucleus. Muscarine chlorlde induced a marked increase of fluorescence intensity in a concentration dependent fashion. The enhancement of fluorescence intensity by muscarine chloride was significantly reduced by thapsigargin (depletor of intracellular Ca2+ store; P0.05). And the increase of fluorescence intensity was also significantly inhibited by pirenzepine (M1 subtype selective antagonist; P0.05).Conclusions The data provide the evidence that muscarinic receptors may induce the increase of intracellular free Ca2+ levels through the Ca2+ release of intracellular Ca2+ stores, in a manner related to M1 and M3 subtypes of muscarinic receptors in rat facial nucleus. Nicotine may increase intracellular free Ca2+ concentrations via the influx of extracellular Ca2+ mainly across L-type voltage-gated Ca2+ channels, in a manner related to the α4β2 subtype of nicotinic receptors.

  13. Alpha-asarone improves striatal cholinergic function and locomotor hyperactivity in Fmr1 knockout mice.

    Science.gov (United States)

    Qiu, Guozhen; Chen, Shengqiang; Guo, Jialing; Wu, Jie; Yi, Yong-Hong

    2016-10-01

    Hyperactivity is a symptom found in several neurological and psychiatric disorders, including Fragile X syndrome (FXS). The animal model of FXS, fragile X mental retardation gene (Fmr1) knockout (KO) mouse, exhibits robust locomotor hyperactivity. Alpha (α)-asarone, a major bioactive component isolated from Acorus gramineus, has been shown in previous studies to improve various disease conditions including central nervous system disorders. In this study, we show that treatment with α-asarone alleviates locomotor hyperactivity in Fmr1 KO mice. To elucidate the mechanism underlying this improvement, we evaluated the expressions of various cholinergic markers, as well as acetylcholinesterase (AChE) activity and acetylcholine (ACh) levels, in the striatum of Fmr1 KO mice. We also analyzed the AChE-inhibitory activity of α-asarone. Striatal samples from Fmr1 KO mice showed decreased m1 muscarinic acetylcholine receptor (m1 mAChR) expression, increased AChE activity, and reduced ACh levels. Treatment with α-asarone improved m1 mAChR expression and ACh levels, and attenuated the increased AChE activity. In addition, α-asarone dose-dependently inhibited AChE activity in vitro. These results indicate that direct inhibition of AChE activity and up-regulation of m1 mAChR expression in the striatum might contribute to the beneficial effects of α-asarone on locomotor hyperactivity in Fmr1 KO mice. These findings might improve understanding of the neurobiological mechanisms responsible for locomotor hyperactivity. PMID:27316341

  14. Hormonal and cholinergic influences on pancreatic lysosomal and digestive enzymes in rats.

    Science.gov (United States)

    Evander, A; Ihse, I; Lundquist, I

    1983-01-01

    Hormonal and cholinergic influences on lysosomal and digestive enzyme activities in pancreatic tissue were studied in normal adult rats. Hormonal stimulation by the cholecystokinin analogue, caerulein, induced a marked enhancement of the activities of cathepsin D and N-acetyl-beta-D-glucosaminidase in pancreatic tissue, whereas the activities of amylase and lipase tended to decrease. Acid phosphatase activity was not affected. Further, caerulein was found to induce a significant increase of cathepsin D output in bile-pancreatic juice. This output largely parallelled that of amylase. Cholinergic stimulation by the muscarinic agonist carbachol, at a dose level giving the same output of amylase as caerulein, did not affect pancreatic activities of cathepsin D and N-acetyl-beta-D-glucosaminidase. Further, cholinergic stimulation induced an increase of amylase activity and a slight decrease of acid phosphatase activity in pancreatic tissue. Lipase activity was not affected. No apparent effect on cathepsin D output in bile-pancreatic juice was encountered after cholinergic stimulation. The activities of neither the digestive nor the lysosomal enzymes were influenced by the administration of secretin. The results suggest a possible lysosomal involvement in caerulein-induced secretion and/or inactivation of pancreatic digestive enzymes, whereas cholinergic stimulation seems to act through different mechanisms.

  15. BMP9 protects septal neurons from axotomy-evoked loss of cholinergic phenotype.

    Directory of Open Access Journals (Sweden)

    Ignacio Lopez-Coviella

    Full Text Available BACKGROUND: Cholinergic projection from the septum to the hippocampus is crucial for normal cognitive function and degeneration of cells and nerve fibers within the septohippocampal pathway contributes to the pathophysiology of Alzheimer's disease. Bone morphogenetic protein (BMP 9 is a cholinergic differentiating factor during development both in vivo and in vitro. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether BMP9 could protect the adult cholinergic septohippocampal pathway from axotomy-evoked loss of the cholinergic phenotype, we performed unilateral fimbria-fornix transection in mice and treated them with a continuous intracerebroventricular infusion of BMP9 for six days. The number of choline acetyltransferase (CHAT-positive cells was reduced by 50% in the medial septal nucleus ipsilateral to the lesion as compared to the intact, contralateral side, and BMP9 infusion prevented this loss in a dose-dependent manner. Moreover, BMP9 prevented most of the decline of hippocampal acetylcholine levels ipsilateral to the lesion, and markedly increased CHAT, choline transporter CHT, NGF receptors p75 (NGFR-p75 and TrkA (NTRK1, and NGF protein content in both the lesioned and unlesioned hippocampi. In addition, BMP9 infusion reduced bilaterally hippocampal levels of basic FGF (FGF2 protein. CONCLUSIONS/SIGNIFICANCE: These data indicate that BMP9 administration can prevent lesion-evoked impairment of the cholinergic septohippocampal neurons in adult mice and, by inducing NGF, establishes a trophic environment for these cells.

  16. Chronic Cerebral Ischaemia Forms New Cholinergic Mechanisms of Learning and Memory

    Directory of Open Access Journals (Sweden)

    E. I. Zakharova

    2010-01-01

    Full Text Available The purpose of this research was a comparative analysis of cholinergic synaptic organization following learning and memory in normal and chronic cerebral ischaemic rats in the Morris water maze model. Choline acetyltransferase and protein content were determined in subpopulations of presynapses of “light” and “heavy” synaptosomal fractions of the cortex and the hippocampus, and the cholinergic projective and intrinsic systems of the brain structures were taken into consideration. We found a strong involvement of cholinergic systems, both projective and intrinsic, in all forms of cognition. Each form of cognition had an individual cholinergic molecular profile and the cholinergic synaptic compositions in the ischaemic rat brains differed significantly from normal ones. Our data demonstrated that under ischaemic conditions, instead of damaged connections new key synaptic relationships, which were stable against pathological influences and able to restore damaged cognitive functions, arose. The plasticity of neurochemical links in the individual organization of certain types of cognition gave a new input into brain pathology and can be used in the future for alternative corrections of vascular and other degenerative dementias.

  17. Geodynamic Drivers of Vertical Crustal Motion: Integrating Paleoaltimetry with Basin Development in the Central Andean Plateau of Southern Peru

    Science.gov (United States)

    Sundell, K. E., II; Saylor, J. E.; Lapen, T. J.; Villarreal, D. P.; Styron, R. H.; Horton, B. K.; Cardenas, J.

    2015-12-01

    Determining the spatial and temporal relationships between surface uplift, tectonic subsidence, and exhumation during periods of oblique crustal shortening is essential to discriminating geodynamic processes controlling formation of high topography in the central Andes. Although subsidence analysis is now a standard tool, paleoelevation estimation remains a challenging task, as estimates based on proxy data can be complicated by uncertainties in the relative controls of tectonics and climate. We therefore adopt an approach of combining established tools of subsidence analysis and detrital geochronology with emerging methods of volcanic glass paleoaltimetry, which enables us to explore a broad range of viable interpretations to understand the development of intermontane basins and their relationship to the development of the central Andean plateau. We investigated a suite of temporally overlapping and spatially separate Cenozoic basins spanning the east-west extent of the central Andean plateau in southern Peru. These basins contain an exceptional record of the vertical movements of this region. We calculate sediment accumulation and subsidence rates through decompaction of measured stratigraphic sections, and reconstruct past environmental conditions based on the stable isotopic composition of ancient waters preserved in hydrated volcanic glass. These data and published records of crustal shortening and exhumation show that although paleoaltimetry data in the study areas may be interpreted in various ways, they are best explained by multiple geodynamic processes driving (i) Eocene-early Miocene development of high topography in the Western Cordillera, then (ii) a pulsed middle Miocene-present building of the central Andean plateau from west to east, consistent with global climate changes as well as regional climate shifts driven by topographic development of the Andean orogen.

  18. An integrated ecosystem trophic model for the North and Central Gulf of California: An alternative view for endemic species conservation

    OpenAIRE

    Díaz-Uribe, J. Gabriel; Arreguín Sánchez, Francisco; Lercari-Bernier, Diego; Cruz Escalona, Víctor Hugo; Zetina Rejón, Manuel Jesús; Del Monte Luna, Pablo; Martínez-Aguilar, Susana

    2012-01-01

    Understanding of the intricate interactions of endemic species with anthropogenic impacts of diverse economic interests on ecosystems is of paramount importance to the implementation of effective con-servation programs. A trophic mass-balance model was used to analyze the structural properties of the North and Central Gulf of California (NC-GulfCal) ecosystem, the most important fishing area in Mexico and where conservation efforts for protecting the endangered endemic porpoise known as vaqui...

  19. Foreign Trade of Central Asian Independent States: What is the main trend- Globalization and Regionalization or Re-integration?

    OpenAIRE

    Islamov, Bakhtior

    1999-01-01

    Assessing the most recent data on the foreign trade of the Central Asian states and evaluation its main trends after their independence, the author argues that despite of lack of solid framework the tendency for globalization and regionalization hash been stronger compared to restoration of traditional ties. Elimination of existing institutional, infrastructural and other impediments, as well as proper multilateral regional initiatives could serve for further increase of trade within the regi...

  20. A short-chain α-neurotoxin from Naja naja atra produces potent cholinergic-dependent analgesia

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the analgesia induced by cobrotoxin (CT) from venom of Naja naja atra, and the effects of atropine and naloxone on the antinociceptive activity of CT in rodent pain models. Methods CT was administered intraperitoneally (33.3, 50, 75 μg/kg), intra-cerebral venticularly (2.4 μg/kg) or microinjected into periaqueductal gray ( PAG, 1.2 μg/kg). The antinociceptive action was tested using the hot-plate test and the acetic acid writhing test in mice and rats. The involvement of cholinergic system and the opioid system in CT-induced analgesia was examined by pretreatment of animals with atropine (0.5 mg/kg, im or 10 mg/kg, ip) or naloxone (3 mg/kg, ip). The effect of CT on motor activity was tested using the Animex test. Results CT (33.3, 50 and 75 μg/kg, ip) exhibited a dosedependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. In the mouse acetic acid writhing test, the intra-cerebral ventricle administration of CT 2.4 μg/kg (1/23th of a systemic dose) produced marked analgesic effects. Microinjection of CT 1.2 μg/kg ( 1/46th of systemic dose) into the PAG also elicited a robust analgesic action in the hot-plate test in rats. Atropine at 0.5 mg/kg (im) or naloxone at 3 mg/kg (ip) failed to block the analgesic effects of CT, but atropine at 10 mg/kg (ip) did antagonize the analgesia mediated by CT in the mouse acetic acid writhing test. At the highest effective dose of antinociception (75 μg/kg), CT did not change the spontaneous mobility of mice. Conclusion These results suggest that CT from Naja naja atra venom has analgesic effects. Central nervous system may be involved in CT' analgesic effects and the PAG may be the primary central site where CT exerts its effects. The central cholinergic system but not opioid system appears to be involved in the antinociceptive action of CT.

  1. Axotomy-induced neurotrophic withdrawal causes the loss of phenotypic differentiation and downregulation of NGF signalling, but not death of septal cholinergic neurons

    Directory of Open Access Journals (Sweden)

    Inestrosa Nibaldo C

    2010-01-01

    Full Text Available Abstract Background Septal cholinergic neurons account for most of the cholinergic innervations of the hippocampus, playing a key role in the regulation of hippocampal synaptic activity. Disruption of the septo-hippocampal pathway by an experimental transection of the fimbria-fornix drastically reduces the target-derived trophic support received by cholinergic septal neurons, mainly nerve growth factor (NGF from the hippocampus. Axotomy of cholinergic neurons induces a reduction in the number of neurons positive for cholinergic markers in the medial septum. In several studies, the reduction of cholinergic markers has been interpreted as analogous to the neurodegeneration of cholinergic cells, ruling out the possibility that neurons lose their cholinergic phenotype without dying. Understanding the mechanism of cholinergic neurodegeneration after axotomy is relevant, since this paradigm has been extensively explored as an animal model of the cholinergic impairment observed in neuropathologies such as Alzheimer's disease. The principal aim of this study was to evaluate, using modern quantitative confocal microscopy, neurodegenerative changes in septal cholinergic neurons after axotomy and to assess their response to delayed infusion of NGF in rats. Results We found that there is a slow reduction of cholinergic cells labeled by ChAT and p75 after axotomy. However, this phenomenon is not accompanied by neurodegenerative changes or by a decrease in total neuronal number in the medial septum. Although the remaining axotomized-neurons appear healthy, they are unable to respond to delayed NGF infusion. Conclusions Our results demonstrate that at 3 weeks, axotomized cholinergic neurons lose their cholinergic phenotype without dying and down-regulate their NGF-receptors, precluding the possibility of a response to NGF. Therefore, the physiological role of NGF in the adult septal cholinergic system is to support phenotypic differentiation and not survival

  2. Cerebral cortical astroglia from the trisomy 16 mouse, a model for Down syndrome, produce neuronal cholinergic deficits in cell culture

    OpenAIRE

    Nelson, P. G.; Fitzgerald, S.; Rapoport, S I; Neale, E A; Galdzicki, Z; Dunlap, V.; Bowers, L; v. Agoston, D.

    1997-01-01

    Trisomy 21 (Down syndrome) is associated with a high incidence of Alzheimer disease and with deficits in cholinergic function in humans. We used the trisomy 16 (Ts16) mouse model for Down syndrome to identify the cellular basis for the cholinergic dysfunction. Cholinergic neurons and cerebral cortical astroglia, obtained separately from Ts16 mouse fetuses and their euploid littermates, were cultured in various combinations. Choline acetyltransferase activity and cholinergic neuron number were...

  3. Checks and balances on cholinergic signaling in brain and body function.

    Science.gov (United States)

    Soreq, Hermona

    2015-07-01

    A century after the discovery of acetylcholine (ACh), we recognize both ACh receptors, transporters, and synthesizing and degrading enzymes and regulators of their expression as contributors to cognition, metabolism, and immunity. Recent discoveries indicate that pre- and post-transcriptional ACh signaling controllers coordinate the identity, functioning, dynamics, and brain-to-body communication of cholinergic cells. Checks and balances including epigenetic mechanisms, alternative splicing, and miRNAs may all expand or limit the diversity of these cholinergic components by consistently performing genome-related surveillance. This regulatory network enables homeostatic maintenance of brain-to-body ACh signaling as well as reactions to nicotine, Alzheimer's disease anticholinesterase therapeutics, and agricultural pesticides. Here I review recent reports on the functional implications of these controllers of cholinergic signaling in and out of the brain. PMID:26100140

  4. Cholinergic Neurons - Keeping Check on Amyloid beta in the Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Saak V. Ovsepian

    2013-12-01

    Full Text Available The physiological relevance of the uptake of ligands with no apparent trophic functions via the p75 neurotrophin receptor (p75NTR remains unclear. Herein, we propose a homeostatic role for this in clearance of amyloid β (Aβ in the brain. We hypothesize that uptake of Aβ in conjunction with p75NTR followed by its degradation in lysosomes endows cholinergic basalo-cortical projections enriched in this receptor a facility for maintaining physiological levels of Aβ in target areas. Thus, in addition to the diffuse modulator influence and channeling of extra-thalamic signals, cholinergic innervations could supply the cerebral cortex with an elaborate system for Aβ drainage. Interpreting the emerging relationship of new molecular data with established role of cholinergic modulator system in regulating cortical network dynamics should provide new insights into the brain physiology and mechanisms of neuro-degenerative diseases.

  5. Cholinergic neuromuscular junctions in Brachionus calyciflorus and Lecane quadridentata (Rotifera:Monogononta)

    Institute of Scientific and Technical Information of China (English)

    Ignacio Alejandro Prez-Legaspi; Alma Lilin Guerrero-Barrera; Ivn Jos Galvn-Mendoza; Jos Luis Quintanar; Roberto Rico-Martnez

    2014-01-01

    Objective:To identify the presence of joint muscular and cholinergic systems in two freshwater rotifer species, Brachionus calyciflorus and Lecane quadridentata. Methods: The muscle actin fibers were stained with phalloidin-linked fluorescent dye, and acetylcholine was detected with Amplex Red Acetylcholine/Acetylcholinesterase Assay Kit, and then confocal scanning laser microscopy was used. Results:The musculature of Brachionus calyciflorus showed a pattern similar to other species of the same genus, while that of Lecane quadridentata was different from other rotifer genera described previously. The cholinergic system was determined by co-localization of both muscles and acetylcholine labels in the whole rotifer, suggesting the presence of neuromuscular junctions. Conclusions: The distribution pattern of muscular and acetylcholine systems showed considerable differences between the two species that might be related to different adaptations to particular ecological niches. The confirmation of a cholinergic system in rotifers contributes to the development of potential neuro-pharmacological and toxicological studies using rotifers as model organism.

  6. Selective Activation of Cholinergic Interneurons Enhances Accumbal Phasic Dopamine Release: Setting the Tone for Reward Processing

    Directory of Open Access Journals (Sweden)

    Roger Cachope

    2012-07-01

    Full Text Available Dopamine plays a critical role in motor control, addiction, and reward-seeking behaviors, and its release dynamics have traditionally been linked to changes in midbrain dopamine neuron activity. Here, we report that selective endogenous cholinergic activation achieved via in vitro optogenetic stimulation of nucleus accumbens, a terminal field of dopaminergic neurons, elicits real-time dopamine release. This mechanism occurs via direct actions on dopamine terminals, does not require changes in neuron firing within the midbrain, and is dependent on glutamatergic receptor activity. More importantly, we demonstrate that in vivo selective activation of cholinergic interneurons is sufficient to elicit dopamine release in the nucleus accumbens. Therefore, the control of accumbal extracellular dopamine levels by endogenous cholinergic activity results from a complex convergence of neurotransmitter/neuromodulator systems that may ultimately synergize to drive motivated behavior.

  7. 'Integration'

    DEFF Research Database (Denmark)

    Olwig, Karen Fog

    2011-01-01

    , while the countries have adopted disparate policies and ideologies, differences in the actual treatment and attitudes towards immigrants and refugees in everyday life are less clear, due to parallel integration programmes based on strong similarities in the welfare systems and in cultural notions of...

  8. Sexually dimorphic effects of the Lhx7 null mutation on forebrain cholinergic function.

    Science.gov (United States)

    Fragkouli, A; Stamatakis, A; Zographos, E; Pachnis, V; Stylianopoulou, F

    2006-01-01

    It has been reported recently that mice lacking both alleles of the LIM-homeobox gene Lhx7, display dramatically reduced number of forebrain cholinergic neurons. In the present study, we investigated whether the Lhx7 mutation affects male and female mice differently, given the fact that gender differences are consistently observed in forebrain cholinergic function. Our results show that in adult male as well as female Lhx7 homozygous mutants there is a dramatic loss of choline acetyltransferase immunoreactive forebrain neurons, both projection and interneurons. The reduction of forebrain choline acetyltransferase immunoreactive neurons in Lhx7 homozygous mutants is accompanied by a decrease of acetylcholinesterase histochemical staining in all forebrain cholinergic neuron target areas of both male and female homozygous mutants. Furthermore, there was an increase of M1-, but not M2-, muscarinic acetylcholine receptor binding site density in the somatosensory cortex and basal ganglia of only the female homozygous mutant mice. Such an increase can be regarded as a mechanism acting to compensate for the dramatically reduced cholinergic input, raising the possibility that the forebrain cholinergic system in female mice may be more plastic and responsive to situations of limited neurotransmitter availability. Finally, our study provides additional data for the sexual dimorphism of the forebrain cholinergic system, as female mice appear to have a lower density of M1-muscarinic acetylcholine receptors in the striatal areas of the basal ganglia and a higher density of M2-muscarinic acetylcholine receptors, in a number of cortical areas, as well as the striatal areas of the basal ganglia. PMID:16338089

  9. State dependency of the effects of microinjection of cholinergic drugs into the nucleus pontis oralis.

    Science.gov (United States)

    López-Rodríguez, F; Kohlmeier, K; Morales, F R; Chase, M H

    1994-06-27

    The microinjection of cholinergic drugs into the pontine reticular formation elicits active sleep-like states that are comprised of the principal physiological patterns of activity that characterize naturally-occurring active sleep, i.e., EEG desynchronization, PGO waves, rapid eye movements and atonia. We have reported that other behavioral states arise even when cholinergic drugs are injected into the exact same reticular location. The present study was conducted to explore the basis for the differences in the drug effect. A combination of acetylcholine and neostigmine was injected by microiontophoresis into the dorsal region of the nucleus pontis oralis in four chronic, unanesthetized cats. The states that were induced by cholinergic drug injection depended on the state of the animal at the time of the injection. When the animal was awake, cholinergic injections resulted in a waking-dissociated state, which was characterized by EEG desynchronization and muscle atonia in a cat that appeared to be awake and was able to track objects in its visual field. If the cat was in quiet sleep at the time of the injection, an active sleep-like state followed that was indistinguishable from naturally-occurring active sleep; on a few occasions following cholinergic injections during quiet sleep there was a quiet sleep-dissociated state, which was characterized by PGO waves and muscle atonia in the cat that by other indices appeared to be in quiet sleep. The results of this study indicate that the state of the animal at the time of drug injection is a critical variable that influences the responses which are induced by cholinergic stimulation of the pontine reticular formation. PMID:7953643

  10. Ventral tegmental area cholinergic mechanisms mediate behavioral responses in the forced swim test.

    Science.gov (United States)

    Addy, N A; Nunes, E J; Wickham, R J

    2015-07-15

    Recent studies revealed a causal link between ventral tegmental area (VTA) phasic dopamine (DA) activity and pro-depressive and antidepressant-like behavioral responses in rodent models of depression. Cholinergic activity in the VTA has been demonstrated to regulate phasic DA activity, but the role of VTA cholinergic mechanisms in depression-related behavior is unclear. The goal of this study was to determine whether pharmacological manipulation of VTA cholinergic activity altered behavioral responding in the forced swim test (FST) in rats. Here, male Sprague-Dawley rats received systemic or VTA-specific administration of the acetylcholinesterase inhibitor, physostigmine (systemic; 0.06 or 0.125mg/kg, intra-cranial; 1 or 2μg/side), the muscarinic acetylcholine receptor (AChR) antagonist scopolamine (2.4 or 24μg/side), or the nicotinic AChR antagonist mecamylamine (3 or 30μg/side), prior to the FST test session. In control experiments, locomotor activity was also examined following systemic and intra-cranial administration of cholinergic drugs. Physostigmine administration, either systemically or directly into the VTA, significantly increased immobility time in FST, whereas physostigmine infusion into a dorsal control site did not alter immobility time. In contrast, VTA infusion of either scopolamine or mecamylamine decreased immobility time, consistent with an antidepressant-like effect. Finally, the VTA physostigmine-induced increase in immobility was blocked by co-administration with scopolamine, but unaltered by co-administration with mecamylamine. These data show that enhancing VTA cholinergic tone and blocking VTA AChRs has opposing effects in FST. Together, the findings provide evidence for a role of VTA cholinergic mechanisms in behavioral responses in FST.

  11. Integral Action: Management Tool for Municipal Governments Centralized by the National Policy of Territorial Consolidation and Reconstruction

    Directory of Open Access Journals (Sweden)

    Orlando Antonio Mejía Quintero

    2015-01-01

    Full Text Available Integral action has been a key tool for social development, regarding the achievements of the national government to recover legitimacy and governability. Since its beginning in 2002 and up to date, the consolidation process—represented in the National Policy of Territorial Consolidation and Reconstruction (NPTCR— has presented changes in its strategy, in line with current circumstances. This article is theoretically based on the concepts of legitimacy and governability and on the doctrine of integral action of the Armed Forces, complemented with the experience of officers who worked on this strategy or currently run it. Thus, this study offers recommendations to the national government for decision making in modifying the development of NPTCR, taking into account the current historical moment.

  12. Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage

    Institute of Scientific and Technical Information of China (English)

    Yifan He; Jihong Zhu; Fang Huang; Liu Qin; Wenguo Fan; Hongwen He

    2014-01-01

    The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltrans-ferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and

  13. Quantification of Glacier Depletion in the Central Tibetan Plateau by Using Integrated Satellite Remote Sensing and Gravimetry

    Science.gov (United States)

    Tseng, K.-H.; Liu, K. T.; Shum, C. K.; Jia, Y.; Shang, K.; Dai, C.

    2016-06-01

    Glaciers over the Tibetan Plateau have experienced accelerated depletion in the last few decades due primarily to the global warming. The freshwater drained into brackish lakes is also observed by optical remote sensing and altimetry satellites. However, the actual water storage change is difficult to be quantified since the altimetry or remote sensing only provide data in limited dimensions. The altimetry data give an elevation change of surface while the remote sensing images provide an extent variation in horizontal plane. Hence a data set used to describe the volume change is needed to measure the exact mass transition in a time span. In this study, we utilize GRACE gravimetry mission to quantify the total column mass change in the central Tibetan Plateau, especially focused on the lakes near Tanggula Mountains. By removing these factors, the freshwater storage change of glacier system at study area can be potentially isolated.

  14. Integrative taxonomy of central European parasitic flatworms of the family Prosthogonimidae Lühe, 1909 (Trematoda: Plagiorchiida).

    Science.gov (United States)

    Heneberg, Petr; Sitko, Jiljí; Bizos, Jiří

    2015-10-01

    Species of the family Prosthogonimidae are considered the most pathogenic poultry trematodes worldwide, affecting particularly low intensity farming in rural areas. Adults of Prosthogonimus occur mainly in the bursa of Fabricius, oviduct and cloaca of ducks, geese, fowl and other birds feeding at least occasionally on dragonflies or damselflies (Odonata). We analyzed the central European species of the Prosthogonimidae, namely Prosthogonimus cuneatus, Prosthogonimus ovatus, Prosthogonimus pellucidus and Prosthogonimus rarus. We sequenced three nuclear (ITS2) and mitochondrial (CO1, ND1) DNA loci of four species isolated from Anas clypeata, Anas strepera, Anas platyrhynchos, Aythya ferina, Passer domesticus and Turdus merula. Intra- and inter-specific sequence variability revealed that all four species represent distinct well-defined entities. Our data, combined with previously published studies, suggest the return of the name Prosthogonimus rarus Braun, 1901 for Schistogonimus rarus (Braun, 1901). The genus name Schistogonimus Lühe, 1909 is considered a junior synonym of Prosthogonimus Lühe, 1899. We identified the existence of two clades, one represented by P. cuneatus and P. pellucidus, and another one formed by P. ovatus and P. rarus. We also provide comparative measurements of these four central European prosthogonimids, and address their tissue specificity, host-specific prevalence (based on the extensive bird cohort examined in years 1962-2014), and for some bird hosts we address also differences in the prevalence of Prosthogonimus spp. in natural and near-natural wetlands in comparison with fishponds utilized for intense carp production. We provide an updated key to European Prosthogonimus spp. based on their morphological characters. PMID:25724855

  15. 胆碱能抗炎通路的研究进展%Cholinergic anti-inflammatory pathway:research advances

    Institute of Scientific and Technical Information of China (English)

    赵建; 丁日高

    2014-01-01

    The cholinergic anti-infla mmatory pathway regulates the inflammation response to injury,pathogens,tissue ischemia et al,by stimulating the peripheral vagus or centrally acting muscarinic agonists. It can regulate the systemic inflammation rapidly and directly,and inhibit the lethal effect of biotoxins (e.g,lipopolysaccharide). Based on the recent advancements,the historical origins and constitution of the cholinergic anti-inflammatory pathway,the connection between vagus and spleen,and the relationship with the inflammatory reflex are summarized.%胆碱能抗炎通路通过刺激外周迷走神经或应用中枢性毒蕈碱受体激动剂等,对损伤、病原体或组织缺血所致炎症反应发挥免疫调节作用。与体液抗炎通路相比,胆碱能抗炎通路反应时间非常短,它能够快速而直接地调节全身性炎症反应,抑制生物毒素的致死效应。本文对胆碱能抗炎通路的研究起源和构成,迷走神经与脾、炎性反射的关系进行综述。

  16. Technical and environmental aspects of combined cycle power stations with integrated gasification (CCGI); Aspectos tecnicos y medioambientales de las centrales de ciclo combinado con gasificacion integrada (CCGI)

    Energy Technology Data Exchange (ETDEWEB)

    Beltran Mora, Hector Alejandro; Urias Romero, Francisco [Facultad de Ingenieria, Universidad Nacional Autonoma de Mexico, Mexico, D.F. (Mexico)

    2004-06-15

    A description is presented of the operation of the Combined Cycle Power Stations with Integrated Gasification (CCGI) where the use of solid fuels (coal, vacuum residues, petroleum coke, and biomass) or liquids is possible in a thermal power station with the efficiency and many of the own environmental benefits of the combined cycles. The gasification process is analyzed, that is a thermo-chemical process by means of which a fuel that is in solid state or liquid becomes to the gaseous state by means of a partial oxidation and the obtained gas of this process is called synthesis gas (syngas, by its abbreviations in English) that is used in Combined Cycle Power Stations as a substitute for the natural gas. Also the other components of this type of power stations are shown, such as the air separating unit, and some of the modifications that are due to make to adapt a gas turbine so that it uses syngas, and the considerations of their integration with the air separating unit to optimize the operation of the plant are detailed. A comparison of efficiency values of power stations CCGI with the conventional carbon-electric and the power stations of combined cycle that use natural gas is also shown. Finally the emissions of pollutants of SO{sub 2}, NO{sub x} and CO{sub 2} are analyzed. The possibility of using fuels like petroleum coke and vacuum tower residues that are produced in the Cadereyta refinery is studied for the possible construction of a CCGI power station in Mexico. [Spanish] Se presenta la descripcion del funcionamiento de las centrales ciclo combinado con gasificacion integrada (CCGI) donde es posible el uso de combustibles solidos (carbon, residuos de vacio, coque de petroleo, biomasa) o liquidos en una central termica con la eficiencia y muchos de los beneficios ambientales propios de los ciclos combinados. Se analiza el proceso de gasificacion, que es un proceso termoquimico mediante el cual se convierte un combustible que se encuentra en estado solido o

  17. An integrated framework to assess adaptation options to climate change impacts in an irrigated basin in Central North Chile

    Science.gov (United States)

    Vicuna, S.; Melo, O.; Meza, F. J.; Alvarez, P.; Maureira, F.; Sanchez, A.; Tapia, A.; Cortes, M.; Dale, L. L.

    2013-12-01

    Future climate conditions could potentially affect water supply and demand on water basins throughout the world but especially on snowmelt-driven agriculture oriented basins that can be found throughout central Chile. Increasing temperature and reducing precipitation will affect both the magnitude and timing of water supply this part of the world. Different adaptation strategies could be implemented to reduce the impacts of such scenarios. Some could be incorporated as planned policies decided at the basin or Water Use Organization levels. Examples include changing large scale irrigation infrastructure (reservoirs and main channels) either physically or its operation. Complementing these strategies it is reasonable to think that at a disaggregated level, farmers would also react (adapt) to these new conditions using a mix of options to either modify their patterns of consumption (irrigation efficiency, crop mix, crop area reduction), increase their ability to access new sources of water (groundwater, water markets) or finally compensate their expected losses (insurance). We present a modeling framework developed to represent these issues using as a case study the Limarí basin located in Central Chile. This basin is a renowned example of how the development of reservoirs and irrigation infrastructure can reduce climate vulnerabilities allowing the economic development of a basin. Farmers in this basin tackle climate variability by adopting different strategies that depend first on the reservoir water volume allocation rule, on the type and size of investment they have at their farms and finally their potential access to water markets and other water supplies options. The framework developed can be used to study these strategies under current and future climate scenarios. The cornerstone of the framework is an hydrology and water resources model developed on the WEAP platform. This model is able to reproduce the large scale hydrologic features of the basin such as

  18. The subtle body: an interoceptive map of central nervous system function and meditative mind-brain-body integration.

    Science.gov (United States)

    Loizzo, Joseph J

    2016-06-01

    Meditation research has begun to clarify the brain effects and mechanisms of contemplative practices while generating a range of typologies and explanatory models to guide further study. This comparative review explores a neglected area relevant to current research: the validity of a traditional central nervous system (CNS) model that coevolved with the practices most studied today and that provides the first comprehensive neural-based typology and mechanistic framework of contemplative practices. The subtle body model, popularly known as the chakra system from Indian yoga, was and is used as a map of CNS function in traditional Indian and Tibetan medicine, neuropsychiatry, and neuropsychology. The study presented here, based on the Nalanda tradition, shows that the subtle body model can be cross-referenced with modern CNS maps and challenges modern brain maps with its embodied network model of CNS function. It also challenges meditation research by: (1) presenting a more rigorous, neural-based typology of contemplative practices; (2) offering a more refined and complete network model of the mechanisms of contemplative practices; and (3) serving as an embodied, interoceptive neurofeedback aid that is more user friendly and complete than current teaching aids for clinical and practical applications of contemplative practice. PMID:27164469

  19. PREFRONTAL CORTICAL PROJECTIONS TO THE CHOLINERGIC NEURONS IN THE BASAL FOREBRAIN

    NARCIS (Netherlands)

    GAYKEMA, RPA; VANWEEGHEL, R; HERSH, LB; LUITEN, PGM

    1991-01-01

    The prefrontal cortex (PFC) projections to the basal forebrain cholinergic cell groups in the medial septum (MS), vertical and horizontal limbs of the diagonal band of Broca (VDB and HDB), and the magnocellular basal nucleus (MBN) in the rat were investigated by anterograde transport of Phaseolus vu

  20. Cholinergic Septo-Hippocampal Innervation Is Required for Trace Eyeblink Classical Conditioning

    Science.gov (United States)

    Fontan-Lozano, Angela; Troncoso, Julieta; Munera, Alejandro; Carrion, Angel Manuel; Delgado-Garcia, Jose Maria

    2005-01-01

    We studied the effects of a selective lesion in rats, with 192-IgG-saporin, of the cholinergic neurons located in the medial septum/diagonal band (MSDB) complex on the acquisition of classical and instrumental conditioning paradigms. The MSDB lesion induced a marked deficit in the acquisition, but not in the retrieval, of eyeblink classical…

  1. Cholinergic Modulation during Acquisition of Olfactory Fear Conditioning Alters Learning and Stimulus Generalization in Mice

    Science.gov (United States)

    Pavesi, Eloisa; Gooch, Allison; Lee, Elizabeth; Fletcher, Max L.

    2013-01-01

    We investigated the role of cholinergic neurotransmission in olfactory fear learning. Mice receiving pairings of odor and foot shock displayed fear to the trained odor the following day. Pretraining injections of the nicotinic antagonist mecamylamine had no effect on subsequent freezing, while the muscarinic antagonist scopolamine significantly…

  2. Long-Term Effects of Maternal Deprivation on Cholinergic System in Rat Brain

    Directory of Open Access Journals (Sweden)

    Branka Marković

    2014-01-01

    Full Text Available Numerous clinical studies have demonstrated an association between early stressful life events and adult life psychiatric disorders including schizophrenia. In rodents, early life exposure to stressors such as maternal deprivation (MD produces numerous hormonal, neurochemical, and behavioral changes and is accepted as one of the animal models of schizophrenia. The stress induces acetylcholine (Ach release in the forebrain and the alterations in cholinergic neurotransmitter system are reported in schizophrenia. The aim of this study was to examine long-term effects of maternal separation on acetylcholinesterase (AChE activity in different brain structures and the density of cholinergic fibers in hippocampus and retrosplenial (RS cortex. Wistar rats were separated from their mothers on the postnatal day (P 9 for 24 h and sacrificed on P60. Control group of rats was bred under the same conditions, but without MD. Brain regions were collected for AChE activity measurements and morphometric analysis. Obtained results showed significant decrease of the AChE activity in cortex and increase in the hippocampus of MD rats. Density of cholinergic fibers was significantly increased in CA1 region of hippocampus and decreased in RS cortex. Our results indicate that MD causes long-term structure specific changes in the cholinergic system.

  3. Pitx3 deficiency in mice affects cholinergic modulation of GABAergic synapses in the nucleus accumbens

    NARCIS (Netherlands)

    de Rover, Mischa; Lodder, Johannes C.; Smidt, Marten P.; Brussaard, Arjen B.

    2006-01-01

    Pitx3 deficiency in mice affects cholinergic modulation of GABAergic synapses in the nucleus accumbens. J Neurophysiol 96: 2034-2041, 2006. First published July 12, 2006; doi:10.1152/jn.00333.2006. We investigated to what extent Pitx3 deficiency, causing hyperdopaminergic transmission in the nucleus

  4. Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure.

    Science.gov (United States)

    Lara, Aline; Damasceno, Denis D; Pires, Rita; Gros, Robert; Gomes, Enéas R; Gavioli, Mariana; Lima, Ricardo F; Guimarães, Diogo; Lima, Patricia; Bueno, Carlos Roberto; Vasconcelos, Anilton; Roman-Campos, Danilo; Menezes, Cristiane A S; Sirvente, Raquel A; Salemi, Vera M; Mady, Charles; Caron, Marc G; Ferreira, Anderson J; Brum, Patricia C; Resende, Rodrigo R; Cruz, Jader S; Gomez, Marcus Vinicius; Prado, Vania F; de Almeida, Alvair P; Prado, Marco A M; Guatimosim, Silvia

    2010-04-01

    Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling. Gene expression was analyzed by quantitative reverse transcriptase PCR and Western blotting, and the results indicated that VAChT mutant mice have profound cardiac remodeling and reactivation of the fetal gene program. This phenotype was attributable to reduced cholinergic tone, since administration of the cholinesterase inhibitor pyridostigmine for 2 weeks reversed the cardiac phenotype in mutant mice. Our findings provide direct evidence that decreased cholinergic neurotransmission and underlying autonomic imbalance cause plastic alterations that contribute to heart dysfunction.

  5. GABAERGIC MODULATION OF STRIATAL CHOLINERGIC INTERNEURONS - AN IN-VIVO MICRODIALYSIS STUDY

    NARCIS (Netherlands)

    DEBOER, P; WESTERINK, BHC

    1994-01-01

    Striatal cholinergic interneurons have been shown to receive input from striatal gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on two different types of receptors, the GABA(A) and the GABA(B) receptor. Using in vivo microdialysis, we have studied the effect of intrast

  6. Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimer's disease

    OpenAIRE

    Smith, Gwenn S.; Kramer, Elisse; Ma, Yilong; Hermann, Carol R.; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David

    2009-01-01

    Pre-clinical and human neuropharmacological evidence suggests a role of cholinergic modulation of monoamines as a pathophysiological and therapeutic mechanism in Alzheimer's disease. The present study measured the effects of treatment with the cholinesterase inhibitor and nicotinic receptor modulator, galantamine, on the cerebral metabolic response to the selective serotonin reuptake inhibitor, citalopram. Seven probable Alzheimer's disease patients and seven demographically comparable contro...

  7. Activation of vascular cholinergic and adrenergic receptors induced by gamma rays

    International Nuclear Information System (INIS)

    Activation of vascular cholinergic receptors and adrenoceptors plays an important role in vasomotoricity and peripheric vascular resistance. These factors are essential in maintaining a stable blood pressure. The aim of this study is to investigate the radiosensitivity differences between vascular cholinergic receptors and adrenoceptors, and consequently to determinate the effects of ionizing radiation (whole body irradiation) on contractile response regulation of vascular smooth muscle fibers VSMF isolated from rat portal vein. Our results show that Clonidine, (non-specific adrenergic agonist), and phenylephrine which is more specific α1-adrenoceptor agonist, increase the VSMF contractions. The maximum effect is obtained at 10-5 - 3.10-5 M. On irradiated rats (1-3-5 Gy), there is an important shift thus, the maximal response (Emax) can be obtained in lower concentrations of clonidine and phenylephrine. Irradiation deceases the contractile responses of VSMF mediated by cholinergic stimulation, in a dose dependant manner. With Emax 1 Gy>Emax 3 Gy>Emax 5 Gy. Irradiated muscular fibers became less sensitive to acetylcholine, thus 3.10-8 M. A. ch induced more than 50% of contraction force increase in normal conditions. This concentration induce generally a negligible effect after irradiation. The results reveal the existence of radiosensitivity differences between vascular cholinergic and adrenergic receptors. (author)

  8. Cholinergic involvement in vascular and glucoregulatory actions of insulin in rats.

    Science.gov (United States)

    Lévesque, Martin; Santuré, Marta; Pitre, Maryse; Nadeau, André; Bachelard, Hélène

    2006-02-01

    This study was designed to test the glucose metabolic and vasodilator actions of insulin in rats and its relation to cholinergic system-dependent mechanisms. The first group of rats had pulsed Doppler flow probes and intravascular catheters implanted to determine blood pressure, heart rate, and regional blood flows. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp technique carried out in the absence or presence of atropine. The second group of rats was used to determine the cholinergic contribution to in vivo insulin-mediated glucose utilization in individual muscles. Glucose uptake was examined by using [(3)H]2-deoxy-D-glucose. Muscarinic cholinergic blockade was found to significantly (P = 0.002) reduce insulin sensitivity and to completely abrogate the renal (P = 0.008) and hindquarter (P = 0.02) vasodilator responses to euglycemic infusion of insulin. A significant reduction in insulin-stimulated in vivo glucose uptake was also noted in soleus (P = 0.006), quadriceps (P = 0.03), gastrocnemius (P = 0.02), and extensor digitorum longus (EDL) (P = 0.001) muscles, when insulin was infused at a rate of 4 mU . kg(-1) . min(-1), whereas at the rate of 16 mU . kg(-1) . min(-1), a significant reduction in glucose uptake was only observed in EDL (P = 0.03) and quadriceps (P = 0.01) muscles. Together, these results demonstrate a potential role for cholinergic involvement with physiological insulin actions in glucose clearance and blood flow regulation in rats.

  9. Degeneration of beta-amyloid-associated cholinergic structures in transgenic APP SW mice.

    Science.gov (United States)

    Lüth, Hans-Joachim; Apelt, Jenny; Ihunwo, Amadi O; Arendt, Thomas; Schliebs, Reinhard

    2003-07-01

    Cholinergic dysfunction is a consistent feature of Alzheimer's disease, and the interrelationship between beta-amyloid deposits, inflammation and early cholinergic cell loss is still not fully understood. To characterize the mechanisms by which beta-amyloid and pro-inflammatory cytokines may exert specific degenerating actions on cholinergic cells ultrastructural investigations by electron microscopy were performed in brain sections from transgenic Tg2576 mice that express the Swedish double mutation of the human amyloid precursor protein and progressively develop beta-amyloid plaques during aging. Both light and electron microscopical investigations of the cerebral cortex of 19-month-old transgenic mice revealed a number of pathological tissue responses in close proximity of beta-amyloid plaques, such as activated microglia, astroglial proliferation, increased number of fibrous astrocytes, brain edema, degeneration of nerve cells, dendrites and axon terminals. Ultrastructural detection of choline acetyl transferase (ChAT)-immunostaining in cerebral cortical sections of transgenic mice clearly demonstrated degeneration of ChAT-immunoreactive fibres in the environment of beta-amyloid plaques and activated glial cells suggesting a role of beta-amyloid and/or inflammation in specific degeneration of cholinergic synaptic structures. PMID:12788508

  10. Hippocampal cholinergic interneurons visualized with the choline acetyltransferase promoter: anatomical distribution, intrinsic membrane properties, neurochemical characteristics, and capacity for cholinergic modulation

    Directory of Open Access Journals (Sweden)

    Feng eYi

    2015-03-01

    Full Text Available Release of acetylcholine (ACh in the hippocampus (HC occurs during exploration, arousal, and learning. Although the medial septum-diagonal band of Broca (MS-DBB is the major extrinsic source of cholinergic input to the HC, cholinergic neurons intrinsic to the HC also exist but remain poorly understood. Here, ChAT-tauGFP and ChAT-CRE/Rosa26YFP (ChAT-Rosa mice were examined in HC. The HC of ChAT-tauGFP mice was densely innervated with GFP-positive axons, often accompanied by large GFP-positive structures, some of which were Neurotrace/DAPI-negative and likely represent large axon terminals. In the HC of ChAT-Rosa mice, ChAT-YFP cells were Neurotrace-positive and more abundant in CA3 and dentate gyrus than CA1 with partial overlapping with calretinin/VIP. Moreover, an anti-ChAT antibody consistently showed ChAT immunoreactivity in ChAT-YFP cells from MS-DBB but rarely from HC. Furthermore, ChAT-YFP cells from CA1 stratum radiatum/stratum lacunosum moleculare (SR/SLM exhibited a stuttering firing phenotype but a delayed firing phenotype in stratum pyramidale (SP of CA3. Input resistance and capacitance were also different between CA1 SR/LM and CA3 SP ChAT-YFP cells. Bath application of ACh increased firing frequency in all ChAT-YFP cells; however, cholinergic modulation was larger in CA1 SR/SLM than CA3 SP ChAT-YFP cells. Finally, CA3 SP ChAT-YFP cells exhibited a wider AP half-width and weaker cholinergic modulation than YFP-negative CA3 pyramidal cells. Consistent with CRE expression in a subpopulation of principal cells, optogenetic stimulation evoked glutamatergic postsynaptic currents in CA1 SR/SLM interneurons. In conclusion, the presence of fluorescently labeled hippocampal cells common to both ChAT-Rosa and ChAT-tauGFP mice are in good agreement with previous reports on the existence of cholinergic interneurons, but both transgenic mouse lines exhibited unexpected anatomical features that departed considerably from earlier observations.

  11. The Cholinergic Signaling Responsible for the Expression of a Memory-Related Protein in Primary Rat Cortical Neurons.

    Science.gov (United States)

    Chen, Tsan-Ju; Chen, Shun-Sheng; Wang, Dean-Chuan; Hung, Hui-Shan

    2016-11-01

    Cholinergic dysfunction in the brain is closely related to cognitive impairment including memory loss. In addition to the degeneration of basal forebrain cholinergic neurons, deficits in the cholinergic receptor signaling may also play an important role. In the present study, to examine the cholinergic signaling pathways responsible for the induction of a memory-related postsynaptic protein, a cholinergic agonist carbachol was used to induce the expression of activity-regulated cytoskeleton associated protein (Arc) in primary rat cortical neurons. After pretreating neurons with various antagonists or inhibitors, the levels of carbachol-induced Arc protein expression were detected by Western blot analysis. The results show that carbachol induces Arc protein expression mainly through activating M1 acetylcholine receptors and the downstream phospholipase C pathway, which may lead to the activation of the MAPK/ERK signaling pathway. Importantly, carbachol-mediated M2 receptor activation exerts negative effects on Arc protein expression and thus counteracts the enhanced effects of M1 activation. Furthermore, it is suggested for the first time that M1-mediated enhancement of N-methyl-D-aspartate receptor (NMDAR) responses, leading to Ca(2+) entry through NMDARs, contributes to carbachol-induced Arc protein expression. These findings reveal a more complete cholinergic signaling that is responsible for carbachol-induced Arc protein expression, and thus provide more information for developing treatments that can modulate cholinergic signaling and consequently alleviate cognitive impairment. J. Cell. Physiol. 231: 2428-2438, 2016. © 2016 Wiley Periodicals, Inc. PMID:26895748

  12. Quantification and regionalization of groundwater recharge in South-Central Kansas: Integrating field characterization, statistical analysis, and GIS

    Science.gov (United States)

    Sophocleous, M.

    2000-01-01

    A practical methodology for recharge characterization was developed based on several years of field-oriented research at 10 sites in the Great Bend Prairie of south-central Kansas. This methodology combines the soil-water budget on a storm-by-storm year-round basis with the resulting watertable rises. The estimated 1985-1992 average annual recharge was less than 50mm/year with a range from 15 mm/year (during the 1998 drought) to 178 mm/year (during the 1993 flood year). Most of this recharge occurs during the spring months. To regionalize these site-specific estimates, an additional methodology based on multiple (forward) regression analysis combined with classification and GIS overlay analyses was developed and implemented. The multiple regression analysis showed that the most influential variables were, in order of decreasing importance, total annual precipitation, average maximum springtime soil-profile water storage, average shallowest springtime depth to watertable, and average springtime precipitation rate. Therefore, four GIS (ARC/INFO) data "layers" or coverages were constructed for the study region based on these four variables, and each such coverage was classified into the same number of data classes to avoid biasing the results. The normalized regression coefficients were employed to weigh the class rankings of each recharge-affecting variable. This approach resulted in recharge zonations that agreed well with the site recharge estimates. During the "Great Flood of 1993," when rainfall totals exceeded normal levels by -200% in the northern portion of the study region, the developed regionalization methodology was tested against such extreme conditions, and proved to be both practical, based on readily available or easily measurable data, and robust. It was concluded that the combination of multiple regression and GIS overlay analyses is a powerful and practical approach to regionalizing small samples of recharge estimates.

  13. Integration of stress and leptin signaling by CART producing neurons in the rodent midbrain centrally projecting Edinger-Westphal nucleus

    Directory of Open Access Journals (Sweden)

    Lu eXu

    2014-03-01

    Full Text Available Leptin targets the brain to regulate feeding, neuroendocrine function and metabolism. The leptin receptor is present in hypothalamic centers controlling energy metabolism as well as in the centrally projecting Edinger-Westphal nucleus (EWcp, a region implicated in the stress response and in various aspects of stress-related behaviors. We hypothesized that the stress response by cocaine- and amphetamine-regulated transcript (CART-producing EWcp-neurons would depend on the animal’s energy state. To test this hypothesis, we investigated the effects of changes in energy state (mimicked by low, normal and high leptin levels, which were achieved by 24h fasting, normal chow and leptin injection, respectively on the response of CART neurons in the EWcp of rats subjected or not to acute restraint stress. Our data show that leptin treatment alone significantly increases CART mRNA expression in the rat EWcp and that in leptin receptor deficient (db/db mice, the number of CART producing neurons in this nucleus is reduced. This suggests that leptin has a stimulatory effect on the production of CART in the EWcp under non-stressed condition. Under stressed condition, however, leptin blunts stress-induced activation of EWcp neurons and decreases their CART mRNA expression. Interestingly, fasting, does not influence the stress-induced activation of EWcp-neurons, and specifically EWcp-CART neurons are not activated. These results suggest that the stress response by the EWcp depends to some degree on the animal’s energy state, a mechanism that may contribute to a better understanding of the complex interplay between obesity and stress.

  14. Postlesion estradiol treatment increases cortical cholinergic innervations via estrogen receptor-α dependent nonclassical estrogen signaling in vivo.

    Science.gov (United States)

    Koszegi, Zsombor; Szego, Éva M; Cheong, Rachel Y; Tolod-Kemp, Emeline; Ábrahám, István M

    2011-09-01

    17β-Estradiol (E2) treatment exerts rapid, nonclassical actions via intracellular signal transduction system in basal forebrain cholinergic (BFC) neurons in vivo. Here we examined the effect of E2 treatment on lesioned BFC neurons in ovariectomized mice and the role of E2-induced nonclassical action in this treatment. Mice given an N-methyl-d-aspartic acid (NMDA) injection into the substantia innominata-nucleus basalis magnocellularis complex (SI-NBM) exhibited cholinergic cell loss in the SI-NBM and ipsilateral cholinergic fiber loss in the cortex. A single injection of E2 after NMDA lesion did not have an effect on cholinergic cell loss in the SI-NBM, but it restored the ipsilateral cholinergic fiber density in the cortex in a time- and dose-dependent manner. The most effective cholinergic fiber restoration was observed with 33 ng/g E2 treatment at 1 h after NMDA lesion. The E2-induced cholinergic fiber restoration was absent in neuron-specific estrogen receptor-α knockout mice in vivo. Selective activation of nonclassical estrogen signaling in vivo by estren induced E2-like restorative actions. Selective blockade of the MAPK or protein kinase A pathway in vivo prevented E2's ability to restore cholinergic fiber loss. Finally, studies in intact female mice revealed an E2-induced restorative effect that was similar to that of E2-treated ovariectomized mice. These observations demonstrate that a single E2 treatment restores the BFC fiber loss in the cortex, regardless of endogenous E2 levels. They also reveal the critical role of nonclassical estrogen signaling via estrogen receptor-α and protein kinase A-MAPK pathways in E2-induced restorative action in the cholinergic system in vivo.

  15. Endogenous cholinergic input to the pontine REM sleep generator is not required for REM sleep to occur.

    Science.gov (United States)

    Grace, Kevin P; Vanstone, Lindsay E; Horner, Richard L

    2014-10-22

    Initial theories of rapid eye movement (REM) sleep generation posited that induction of the state required activation of the pontine subceruleus (SubC) by cholinergic inputs. Although the capacity of cholinergic neurotransmission to contribute to REM sleep generation has been established, the role of cholinergic inputs in the generation of REM sleep is ultimately undetermined as the critical test of this hypothesis (local blockade of SubC acetylcholine receptors) has not been rigorously performed. We used bilateral microdialysis in freely behaving rats (n = 32), instrumented for electroencephalographic and electromyographic recording, to locally manipulate neurotransmission in the SubC with select drugs. As predicted, combined microperfusion of D-AP5 (glutamate receptor antagonist) and muscimol (GABAA receptor agonist) in the SubC virtually eliminated REM sleep. However, REM sleep was not reduced by scopolamine microperfusion in this same region, at a concentration capable of blocking the effects of cholinergic receptor stimulation. This result suggests that transmission of REM sleep drive to the SubC is acetylcholine-independent. Although SubC cholinergic inputs are not majorly involved in REM sleep generation, they may perform a minor function in the reinforcement of transitions into REM sleep, as evidenced by increases in non-REM-to-REM sleep transition duration and failure rate during cholinergic receptor blockade. Cholinergic receptor antagonism also attenuated the normal increase in hippocampal θ oscillations that characterize REM sleep. Using computational modeling, we show that our in vivo results are consistent with a mutually excitatory interaction between the SubC and cholinergic neurons where, importantly, cholinergic neuron activation is gated by SubC activity.

  16. Integrating Kinetic Model of E. coli with Genome Scale Metabolic Fluxes Overcomes Its Open System Problem and Reveals Bistability in Central Metabolism.

    Directory of Open Access Journals (Sweden)

    Ahmad A Mannan

    Full Text Available An understanding of the dynamics of the metabolic profile of a bacterial cell is sought from a dynamical systems analysis of kinetic models. This modelling formalism relies on a deterministic mathematical description of enzyme kinetics and their metabolite regulation. However, it is severely impeded by the lack of available kinetic information, limiting the size of the system that can be modelled. Furthermore, the subsystem of the metabolic network whose dynamics can be modelled is faced with three problems: how to parameterize the model with mostly incomplete steady state data, how to close what is now an inherently open system, and how to account for the impact on growth. In this study we address these challenges of kinetic modelling by capitalizing on multi-'omics' steady state data and a genome-scale metabolic network model. We use these to generate parameters that integrate knowledge embedded in the genome-scale metabolic network model, into the most comprehensive kinetic model of the central carbon metabolism of E. coli realized to date. As an application, we performed a dynamical systems analysis of the resulting enriched model. This revealed bistability of the central carbon metabolism and thus its potential to express two distinct metabolic states. Furthermore, since our model-informing technique ensures both stable states are constrained by the same thermodynamically feasible steady state growth rate, the ensuing bistability represents a temporal coexistence of the two states, and by extension, reveals the emergence of a phenotypically heterogeneous population.

  17. Energy analysis of an improved concept of integrated PV panels in an office building in central Greece

    International Nuclear Information System (INIS)

    During the last decade, steel constructions with glazed facades became popular for commercial buildings in Greece. Moreover, expensive metal, natural stone, marble, ceramic, granite as well as special glass is employed for aesthetic and energy efficiency reasons. This creates opportunities for the introduction of Photovoltaic (PV) modules in double facades. PV modules on south-facing building walls are better placed at a distance from the wall to allow heat rejection and avoid overheating and efficiency loss. Exploiting the rejected heat of the PV modules is also a challenge. In this paper, we examine an improved concept of incorporating PV modules to the south facades of an office building, exploiting both the electricity produced and the heat rejected by the module, to increase building energy efficiency. The PV modules are integrated to the building wall by means of a double facade, which employs intervening ducts for ventilation purposes. The ducts are heating outdoor air, which is employed to cover the ventilation needs of the building, as well as a part of the heating loads. Simulations for typical winter and summer weather and solar insolation conditions are carried out to investigate the building's energy performance improvements.

  18. Time dependent integration of matrix metalloproteinases and their targeted substrates directs axonal sprouting and synaptogenesis following central nervous system injury

    Institute of Scientific and Technical Information of China (English)

    Linda L. Phillips; Julie L. Chan; Adele E. Doperalski; Thomas M. Reeves

    2014-01-01

    Over the past two decades, many investigators have reported how extracellular matrix molecules act to regulate neuroplasticity. The majority of these studies involve proteins which are targets of matrix metalloproteinases. Importantly, these enzyme/substrate interactions can regulate degenerative and regenerative phases of synaptic plasticity, directing axonal and dendritic re-organization after brain insult. The present review ifrst summarizes literature support for the prominent role of matrix metalloproteinases during neuroregeneration, followed by a discussion of data contrasting adaptive and maladaptive neuroplasticity that reveals time-dependent metal-loproteinase/substrate regulation of postinjury synaptic recovery. The potential for these enzymes to serve as therapeutic targets for enhanced neuroplasticity after brain injury is illustrated with experiments demonstrating that metalloproteinase inhibitors can alter adaptive and maladaptive outcome. Finally, the complexity of metalloproteinase role in reactive synaptogenesis is revealed in new studies showing how these enzymes interact with immune molecules to mediate cellu-lar response in the local regenerative environment, and are regulated by novel binding partners in the brain extracellular matrix. Together, these different examples show the complexity with which metalloproteinases are integrated into the process of neuroregeneration, and point to a promising new angle for future studies exploring how to facilitate brain plasticity.

  19. Field Demonstration of Horizontal Infill Drilling Using Cost-effective Integrated Reservoir Modeling--Mississippian Carbonates, Central Kansas

    Energy Technology Data Exchange (ETDEWEB)

    Saibal Bhattacharya

    2005-08-31

    data constraints afflicting mature Mississippian fields. A publicly accessible databank of representative petrophysical properties and relationships was developed to overcome the paucity of such data that is critical to modeling the storage and flow in these reservoirs. Studies in 3 Mississippian fields demonstrated that traditional reservoir models built by integrating log, core, DST, and production data from existing wells on 40-acre spacings are unable to delineate karst-induced compartments, thus making 3D-seismic data critical to characterize these fields. Special attribute analyses on 3D data were shown to delineate reservoir compartments and predict those with pay porosities. Further testing of these techniques is required to validate their applicability in other Mississippian reservoirs. This study shows that detailed reservoir characterization and simulation on geomodels developed by integrating wireline log, core, petrophysical, production and pressure, and 3D-seismic data enables better evaluation of a candidate field for horizontal infill applications. In addition to reservoir compartmentalization, two factors were found to control the economic viability of a horizontal infill well in a mature Mississippian field: (a) adequate reservoir pressure support, and (b) an average well spacing greater than 40-acres.

  20. Integrated characterization of groundwater contamination in an alluvial system. Case study of Allier alluvial aquifer (Massif Central, France).

    Science.gov (United States)

    Mohammed, Nabaz; Celle-Jeanton, Hélène; Batisson, Isabelle; Bardot, Corinne; Colombet, Jonathan; Huneau, Frédéric; Le Coustumer, Philippe; Clauzet, Marie-Laure; Lavastre, Véronique

    2013-04-01

    Hydrogeology is an intrinsically multi-disciplinary field because of the critical role water plays in both human health and natural ecosystems. The NAA (Nappe Alluviale de l'Allier) project proposes an integrated research (hydrodynamic, hydrochemistry and biology) on the shallow aquifer of the Allier River (one of the main tributaries of the Loire River). This aquifer plays an important role in the regional water supply for it represents more than 60% of the total water abstraction. As an example, the sampling site, located near the city of Clermont-Ferrand (France) constitutes the major source of drinking water supply for more than 100 000 inhabitants and then plays a major role on the local socio-economy. A biweekly following sampling, that concerns hydrodynamical parameters, major ions and isotopes (oxygen-18, deuterium and carbon-13), has been achieved during two years on 2 rivers, 1 pond, 2 springs and 17 boreholes with the aim of defining the functioning of the aquifer in terms of quality and quantity of the water resources and then on the main processes that governs hydrodynamic and hydrochemistry. Preliminary results allowed discriminating different origins of groundwater with a part due to surface waters/groundwater interactions and a secondary origin that implies water circulating from the surrounding hills. A monthly following sampling of pesticides, pharmaceuticals and traces ions provides information on contaminants sources. In parallel, the dynamics of the microbial communities (bacteria, pico-cyanobacteria and pico-eukaryotes) was followed by flow cytometer. The bacterial diversity has been measured through PCR-DGGE analysis in order to evaluate the impact of the occurrence of contaminants.

  1. Integrated marketing communications in high-quality hotels of central and southern Dalmatia: a study from the perspective of managers and guests

    Directory of Open Access Journals (Sweden)

    Maja Šerić

    2012-07-01

    Full Text Available Although the implementation of Integrated Marketing Communications (IMC has been studied in different contexts and countries all over the world, further contributions are needed to consolidate the concept. Little research has been done on the integration of marketing communications in tourism-related sectors. Moreover, previous studies have focused mainly on managers’ opinions while overlooking consumers’ perceptions of IMC. The purpose of this research is to study in greater detail the IMC concept in the tourism sector, specifically in the hotels of Central and Southern Dalmatia, from a double perspective: managers-guests. Therefore, managers of 15 high-quality hotels and 118 guests were interviewed during April and May 2010. The results of descriptive statistical analysis showed a high degree of IMC implementation in hotels and a high degree of guests’ perceptions of IMC. However, the Mann-Whitney U test revealed small but significant differences between managers’ and guests’ perceptions of some of the IMC items. The findings of this study are expected to provide useful information to hotel managers, who deal with an increasingly competitive marketplace where traditional marketing approaches are no longer sufficient to differentiate themselves from their competitors. Thus, IMC should be considered as a new approach which might enable hotels to gain competitive advantages.

  2. Detection of visual signals by rats: effects of chlordiazepoxide and cholinergic and adrenergic drugs on sustained attention.

    Science.gov (United States)

    Bushnell, P J; Oshiro, W M; Padnos, B K

    1997-12-01

    Central cholinergic and adrenergic pathways support the attentional processes necessary for detecting and reporting temporally unpredictable stimuli. To assess the functional effects of pharmacological manipulations of these pathways, male Long-Evans rats performed a two-choice, discrete-trial signal-detection task in which food was provided for pressing one lever after presentation of a signal (a 300-ms light flash), and for pressing a second lever at the end of a trial lacking a signal. Seven signal intensities were presented during each 1-h session in a pseudo-random order across three 100-trial blocks. After acquisition of a stable performance baseline, the acute effects of chlordiazepoxide (0, 3, 5, 8 mg/kg i.p.), pilocarpine (0, 1.0, 1.8, 3.0 mg/kg s.c.), scopolamine 0, 0.030, 0.056, 0.100 mg/kg s.c.), nicotine (0, 0.08, 0.25, 0.75 mg/kg s.c.), mecamylamine (0, 1.8, 3.0, 5.6 mg/kg i.p.), clonidine (0, 0.003, 0.010, 0.030 mg/kg s.c.), and idazoxan (0, 1, 3, 10 mg/kg s.c.) were assessed. Five measures of performance were analyzed: response failures; the proportion of "hits" [P(hit): the proportion of correct responses on signal trials]; the proportion of "false alarms" [P(fa): the proportion of incorrect responses on non-signal trials]; and response times (RT) for hits and for correct rejections. All drugs which slowed responding affected RT for hits and correct rejections equivalently, suggesting little or no influence of motor slowing on choice accuracy. Chlordiazepoxide reduced P(hit) at low signal intensities only, without affecting P(fa) or RT, consistent with sensory impairment (reduced visual sensitivity). All other drugs except nicotine reduced P(hit) at high signal intensities preferentially, suggesting a non-visual source of the impairment. Scopolamine, mecamylamine and clonidine affected both P(hit) and P(fa); pilocarpine and idazoxan reduced P(hit) without affecting P(fa). Nicotine at 0.75 mg/kg decreased P(hit) in the first block of trials; at 0

  3. Amyloid-β peptides act as allosteric modulators of cholinergic signalling through formation of soluble BAβACs.

    Science.gov (United States)

    Kumar, Rajnish; Nordberg, Agneta; Darreh-Shori, Taher

    2016-01-01

    Amyloid-β peptides, through highly sophisticated enzymatic machinery, are universally produced and released in an action potential synchronized manner into the interstitial fluids in the brain. Yet no native functions are attributed to amyloid-β. The amyloid-β hypothesis ascribes just neurotoxicity properties through build-up of soluble homomeric amyloid-β oligomers or fibrillar deposits. Apolipoprotein-ε4 (APOE4) allele is the only confirmed genetic risk factor of sporadic Alzheimer's disease; once more it is unclear how it increases the risk of Alzheimer's disease. Similarly, central cholinergic signalling is affected selectively and early in the Alzheimer's disease brain, again why cholinergic neurons show this sensitivity is still unclear. However, the three main known Alzheimer's disease risk factors, advancing age, female gender and APOE4, have been linked to a high apolipoprotein-E and accumulation of the acetylcholine degrading enzyme, butyrylcholinesterase in cerebrospinal fluids of patients. Furthermore, numerous reports indicate that amyloid-β interacts with butyrylcholinesterase and apolipoprotein-E. We have proposed that this interaction leads to formation of soluble ultrareactive acetylcholine-hydrolyzing complexes termed BAβACs, to adjust at demand both synaptic and extracellular acetylcholine signalling. This hypothesis predicted presence of acetylcholine-synthesizing enzyme, choline acetyltransferase in extracellular fluids to allow maintenance of equilibrium between breakdown and synthesis of acetylcholine through continuous in situ syntheses. A recent proof-of-concept study led to the discovery of this enzyme in the human extracellular fluids. We report here that apolipoprotein-E, in particular ε4 isoprotein acts as one of the strongest endogenous anti-amyloid-β fibrillization agents reported in the literature. At biological concentrations, apolipoprotein-E prevented amyloid-β fibrillization for at least 65 h. We show that amyloid

  4. Localization of the M2 muscarinic cholinergic receptor in dendrites, cholinergic terminals, and noncholinergic terminals in the rat basolateral amygdala: An ultrastructural analysis.

    Science.gov (United States)

    Muller, Jay F; Mascagni, Franco; Zaric, Violeta; Mott, David D; McDonald, Alexander J

    2016-08-15

    Activation of M2 muscarinic receptors (M2Rs) in the rat anterior basolateral nucleus (BLa) is critical for the consolidation of memories of emotionally arousing events. The present investigation used immunocytochemistry at the electron microscopic level to determine which structures in the BLa express M2Rs. In addition, dual localization of M2R and the vesicular acetylcholine transporter protein (VAChT), a marker for cholinergic axons, was performed to determine whether M2R is an autoreceptor in cholinergic axons innervating the BLa. M2R immunoreactivity (M2R-ir) was absent from the perikarya of pyramidal neurons, with the exception of the Golgi complex, but was dense in the proximal dendrites and axon initial segments emanating from these neurons. Most perikarya of nonpyramidal neurons were also M2R-negative. About 95% of dendritic shafts and 60% of dendritic spines were M2 immunoreactive (M2R(+) ). Some M2R(+) dendrites had spines, suggesting that they belonged to pyramidal cells, whereas others had morphological features typical of nonpyramidal neurons. M2R-ir was also seen in axon terminals, most of which formed asymmetrical synapses. The main targets of M2R(+) terminals forming asymmetrical (putative excitatory) synapses were dendritic spines, most of which were M2R(+) . The main targets of M2R(+) terminals forming symmetrical (putative inhibitory or neuromodulatory) synapses were unlabeled perikarya and M2R(+) dendritic shafts. M2R-ir was also seen in VAChT(+) cholinergic terminals, indicating a possible autoreceptor role. These findings suggest that M2R-mediated mechanisms in the BLa are very complex, involving postsynaptic effects in dendrites as well as regulating release of glutamate, γ-aminobutyric acid, and acetylcholine from presynaptic axon terminals. J. Comp. Neurol. 524:2400-2417, 2016. © 2016 Wiley Periodicals, Inc. PMID:26779591

  5. Rescue of NGF-deficient mice II: basal forebrain cholinergic projections require NGF for target innervation but not guidance.

    Science.gov (United States)

    Phillips, Heidi S; Nishimura, Merry; Armanini, Mark P; Chen, Karen; Albers, Kathryn M; Davis, Brian M

    2004-04-29

    Basal forebrain cholinergic (BFC) neurons are an important substrate of cognitive function and are hypothesized to require the presence of nerve growth factor (NGF) for survival and target innervation. NGF-deficient mice develop BFC neurons that extend projections into telencephalic targets, but the mice perish before innervation is fully established. Rescue of NGF-deficient mice by transgenic expression of NGF under the keratin promoter yields viable mice with disrupted CNS expression of NGF. In the current study, rescued NGF-deficient mice contain normal numbers of septal cholinergic neurons yet reveal severe compromise of cholinergic innervation of both cortex and hippocampus. Surprisingly, intracerebroventricular infusion of NGF into juvenile mice can induce an essentially normal pattern of cholinergic innervation of the hippocampus. These results indicate that NGF is required for induction of proper innervation by BFC neurons, but that the cellular pattern of expression of this factor is not critical for specifying the distribution of axon terminals. PMID:15093680

  6. Cholinergic neuronal lesions in the medial septum and vertical limb of the diagonal bands of Broca induce contextual fear memory generalization and impair acquisition of fear extinction.

    Science.gov (United States)

    Knox, Dayan; Keller, Samantha M

    2016-06-01

    Previous research has shown that the ventral medial prefrontal cortex (vmPFC) and hippocampus (Hipp) are critical for extinction memory. Basal forebrain (BF) cholinergic input to the vmPFC and Hipp is critical for neural function in these substrates, which suggests BF cholinergic neurons may be critical for extinction memory. In order to test this hypothesis, we applied cholinergic lesions to different regions of the BF and observed the effects these lesions had on extinction memory. Complete BF cholinergic lesions induced contextual fear memory generalization, and this generalized fear was resistant to extinction. Animals with complete BF cholinergic lesions could not acquire cued fear extinction. Restricted cholinergic lesions in the medial septum and vertical diagonal bands of Broca (MS/vDBB) mimicked the effects that BF cholinergic lesions had on contextual fear memory generalization and acquisition of fear extinction. Cholinergic lesions in the horizontal diagonal band of Broca and nucleus basalis (hDBB/NBM) induced a small deficit in extinction of generalized contextual fear memory with no accompanying deficits in cued fear extinction. The results of this study reveal that MS/vDBB cholinergic neurons are critical for inhibition and extinction of generalized contextual fear memory, and via this process, may be critical for acquisition of cued fear extinction. Further studies delineating neural circuits and mechanisms through which MS/vDBB cholinergic neurons facilitate these emotional memory processes are needed. © 2015 Wiley Periodicals, Inc.

  7. Prevenção da infecção da corrente sanguínea relacionada ao cateter venoso central: Uma revisão integrativa | Prevention of bloodstream infection related to central venous catheter: An integrative review

    Directory of Open Access Journals (Sweden)

    Alanna Gomes da Silva

    2016-05-01

    Full Text Available Objetivo: Analisar as produções científicas nacionais e internacionais sobre a adoção aos bundles para prevenção de infecção da corrente sanguínea relacionada ao cateter venoso central em unidade de terapia intensiva adulto. Métodos: Foi realizada uma revisão integrativa da literatura nas bases de dados Pubmed, Cinahl e Science Direct, publicados de 2011 a 2014. Resultados: Foram encontrados 11 artigos e em 100% deles as principais medidas adotadas foram antes da inserção do cateter, sendo: antissepsia da pele, uso de barreira máxima de precaução, preferência pela veia subclávia, higienização prévia das mãos e educação e treinamento dos profissionais de saúde. Conclusões: Os bundles estão sendo utilizados na prática clínica como estratégias para redução das infecções, contudo, as infecções da corrente sanguínea relacionadas a cateter continuam a ocorrer de forma alarmante e com grande impacto no cuidado a saúde. Desse modo, estratégias que apontem subsídios para melhoria da prática clínica e segurança do paciente devem ser incentivadas, sobretudo aquelas voltadas para o período crítico da inserção e manutenção do cateter. -----------------------------------------------------------------------------------------------Objective: To analyze the national and international scientific production on the adoption of bundles to prevent bloodstream infection related to central venous catheters in adult intensive care unit. Methods: An integrative literature review of studies published from 2011 to 2014 was conducted in the databases Pubmed, CINAHL and Science Direct. Results: 11 articles were found. In all of them the principal measures adopted before catheter insertion were: skin antisepsis, use of maximum barrier precaution, preference by the subclavian vein, previous hand hygiene, and education and training of health professionals. Conclusions: The bundles are being used in clinical practice as

  8. Cholinergic-mediated IP3-receptor activation induces long-lasting synaptic enhancement in CA1 pyramidal neurons

    OpenAIRE

    Fernández de Sevilla, D.; Núñez Molina, Ángel; Borde, M.; Malinow, R.; Buño, Washinton

    2008-01-01

    Cholinergic-glutamatergic interactions influence forms of synaptic plasticity that are thought to mediate memory and learning. We tested in vitro the induction of long-lasting synaptic enhancement at Schaffer collaterals by acetylcholine (ACh) at the apical dendrite of CA1 pyramidal neurons and in vivo by stimulation of cholinergic afferents. In vitro ACh induced a Ca2+ wave and synaptic enhancement mediated by insertion of AMPA receptors in spines. Activation of muscarinic ACh receptors (mAC...

  9. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    OpenAIRE

    Monica S Guzman; Xavier De Jaeger; Sanda Raulic; Souza, Ivana A; Li, Alex X.; Susanne Schmid; Menon, Ravi S.; Gainetdinov, Raul R.; Caron, Marc G.; Robert Bartha; Prado, Vania F.; Prado, Marco A. M.

    2011-01-01

    Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent...

  10. A kinetic model for the frequency dependence of cholinergic modulation at hippocampal GABAergic synapses.

    Science.gov (United States)

    Stone, Emily; Haario, Heikki; Lawrence, J Josh

    2014-12-01

    In this paper we use a simple model of presynaptic neuromodulation of GABA signaling to decipher paired whole-cell recordings of frequency dependent cholinergic neuromodulation at CA1 parvalbumin-containing basket cell (PV BC)-pyramidal cell synapses. Variance-mean analysis is employed to normalize the data, which is then used to estimate parameters in the mathematical model. Various parameterizations and hidden parameter dependencies are investigated using Markov Chain Monte Carlo (MCMC) parameter estimation techniques. This analysis reveals that frequency dependence of cholinergic modulation requires both calcium-dependent recovery from depression and mAChR-induced inhibition of presynaptic calcium entry. A reduction in calcium entry into the presynaptic terminal in the kinetic model accounted for the frequency-dependent effects of mAChR activation.

  11. A kinetic model for the frequency dependence of cholinergic modulation at hippocampal GABAergic synapses.

    Science.gov (United States)

    Stone, Emily; Haario, Heikki; Lawrence, J Josh

    2014-12-01

    In this paper we use a simple model of presynaptic neuromodulation of GABA signaling to decipher paired whole-cell recordings of frequency dependent cholinergic neuromodulation at CA1 parvalbumin-containing basket cell (PV BC)-pyramidal cell synapses. Variance-mean analysis is employed to normalize the data, which is then used to estimate parameters in the mathematical model. Various parameterizations and hidden parameter dependencies are investigated using Markov Chain Monte Carlo (MCMC) parameter estimation techniques. This analysis reveals that frequency dependence of cholinergic modulation requires both calcium-dependent recovery from depression and mAChR-induced inhibition of presynaptic calcium entry. A reduction in calcium entry into the presynaptic terminal in the kinetic model accounted for the frequency-dependent effects of mAChR activation. PMID:25445738

  12. Spontaneous Synaptic Activation of Muscarinic Receptors by Striatal Cholinergic Neuron Firing.

    Science.gov (United States)

    Mamaligas, Aphroditi A; Ford, Christopher P

    2016-08-01

    Cholinergic interneurons (CHIs) play a major role in motor and learning functions of the striatum. As acetylcholine does not directly evoke postsynaptic events at most striatal synapses, it remains unclear how postsynaptic cholinergic receptors encode the firing patterns of CHIs in the striatum. To examine the dynamics of acetylcholine release, we used optogenetics and paired recordings from CHIs and medium spiny neurons (MSNs) virally overexpressing G-protein-activated inwardly rectifying potassium (GIRK) channels. Due to the efficient coupling between endogenous muscarinic receptors and GIRK channels, we found that firing of individual CHIs resulted in monosynaptic spontaneous inhibitory post-synaptic currents (IPSCs) in MSNs. Paired CHI-MSN recordings revealed that the high probability of acetylcholine release at these synapses allowed muscarinic receptors to faithfully encode physiological activity patterns from individual CHIs without failure. These results indicate that muscarinic receptors in striatal output neurons reliably decode CHI firing. PMID:27373830

  13. Augmentation of cholinergic-mediated amylase release by forskolin in mouse parotid gland

    International Nuclear Information System (INIS)

    Cholinergic-mediated amylase release in mouse parotid acini was augmented by forskolin; the potency but not the maximal response to carbachol was altered. Amylase released by carbachol plus forskolin was dependent on extracellular calcium and was mimicked by the calcium ionophore, A23187 plus forskolin. Forskolin was also shown to enhance carbachol-stimulated 45Ca2+ uptake into isolated acini. Hydroxylamine, nitroprusside, and 8-bromo-c-GMP each in combination with forskolin mimicked the effects of carbachol plus forskolin on amylase release. In the presence of carbachol (10-8M) forskolin did not augment c-AMP levels. However, in the presence of carbachol (5 x 10-7 M) or hydroxylamine (50 μM) forskolin did significantly augment c-AMP accumulation. These results suggest that calcium and c-GMP may mediate the augmentation of cholinergic-mediated amylase release by effects on c-AMP metabolism. 21 references, 1 figure, 3 tables

  14. Uranium chronic contamination effects on the cholinergic system: in vivo and in vitro approaches

    International Nuclear Information System (INIS)

    Uranium (U) is a heavy metal which occurs naturally in the environment. It is both a chemical and a radiological toxicant. The aim of this work was: (i) to assess the effects of U chronic exposure on the cholinergic system (biosynthesis and breakdown enzymes, receptors and on behaviour of adult, young or predisposed to neuro-degenerative illness (ApoE KO) rodents; (ii) to grasp the neurotoxic effects of U on human neuronal cells. In vivo, this work shows a structure- (cortex more sensitive than hippocampus), rodent model- (young more sensitive than adults), time- (sub-chronic exposure more harmful than chronic exposure), exposure level- and isotope-dependent effect of U. In vitro, the study underlined the neuro-cytotoxic U potential and the presence of uranium precipitates in cells. These results show the deleterious impact of U on neuronal cells, and demonstrate that U induces impairments on the cholinergic system and the behaviour of rodents. (author)

  15. Urotensin II modulates rapid eye movement sleep through activation of brainstem cholinergic neurons

    DEFF Research Database (Denmark)

    Huitron-Resendiz, Salvador; Kristensen, Morten Pilgaard; Sánchez-Alavez, Manuel;

    2005-01-01

    dorsal tegmental nuclei. This distribution suggests that the UII system is involved in functions regulated by acetylcholine, such as the sleep-wake cycle. Here, we tested the hypothesis that UII influences cholinergic PPT neuron activity and alters rapid eye movement (REM) sleep patterns in rats. Local...... administration of UII into the PPT nucleus increases REM sleep without inducing changes in the cortical blood flow. Intracerebroventricular injection of UII enhances both REM sleep and wakefulness and reduces slow-wave sleep 2. Intracerebroventricular, but not local, administration of UII increases cortical...... synaptic transmission because it persisted in the presence of TTX and antagonists of ionotropic glutamate, GABA, and glycine receptors. Collectively, these results suggest that UII plays a role in the regulation of REM sleep independently of its cerebrovascular actions by directly activating cholinergic...

  16. Histamine activates p38 MAP kinase and alters local lamellipodia dynamics, reducing endothelial barrier integrity and eliciting central movement of actin fibers.

    Science.gov (United States)

    Adderley, Shaquria P; Lawrence, Curtis; Madonia, Eyong; Olubadewo, Joseph O; Breslin, Jerome W

    2015-07-01

    The role of the actin cytoskeleton in endothelial barrier function has been debated for nearly four decades. Our previous investigation revealed spontaneous local lamellipodia in confluent endothelial monolayers that appear to increase overlap at intercellular junctions. We tested the hypothesis that the barrier-disrupting agent histamine would reduce local lamellipodia protrusions and investigated the potential involvement of p38 mitogen-activated protein (MAP) kinase activation and actin stress fiber formation. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) expressing green fluorescent protein-actin were studied using time-lapse fluorescence microscopy. The protrusion and withdrawal characteristics of local lamellipodia were assessed before and after addition of histamine. Changes in barrier function were determined using electrical cell-substrate impedance sensing. Histamine initially decreased barrier function, lamellipodia protrusion frequency, and lamellipodia protrusion distance. A longer time for lamellipodia withdrawal and reduced withdrawal distance and velocity accompanied barrier recovery. After barrier recovery, a significant number of cortical fibers migrated centrally, eventually resembling actin stress fibers. The p38 MAP kinase inhibitor SB203580 attenuated the histamine-induced decreases in barrier function and lamellipodia protrusion frequency. SB203580 also inhibited the histamine-induced decreases in withdrawal distance and velocity, and the subsequent actin fiber migration. These data suggest that histamine can reduce local lamellipodia protrusion activity through activation of p38 MAP kinase. The findings also suggest that local lamellipodia have a role in maintaining endothelial barrier integrity. Furthermore, we provide evidence that actin stress fiber formation may be a reaction to, rather than a cause of, reduced endothelial barrier integrity. PMID:25948734

  17. Presenilin-1 Mutation Impairs Cholinergic Modulation of Synaptic Plasticity and Suppresses NMDA Currents in Hippocampus slices

    OpenAIRE

    Wang, Yue; Greig, Nigel H.; Yu, Qian-Sheng; Mattson, Mark P.

    2008-01-01

    Presenilin-1 (PS1) mutations cause many cases of early-onset inherited Alzheimer's disease, in part, by increasing the production of neurotoxic forms of amyloid β-peptide (A β). However, Aβ -independent effects of mutant PS1 on neuronal Ca2+ homeostasis and sensitivity to excitatory neurotransmitters have been reported. Here we show that cholinergic modulation of hippocampal synaptic plasticity is impaired in PS1 mutant knockin (PS1KI) mice. Whereas activation of muscarinic receptors enhances...

  18. Protective role of the cholinergic anti-inflammatory pathway in a mouse model of viral myocarditis.

    Directory of Open Access Journals (Sweden)

    Zheng Cheng

    Full Text Available Activation of the cholinergic anti-inflammatory pathway, which relies on the α7nAchR (alpha 7 nicotinic acetylcholine receptor, has been shown to decrease proinflammatory cytokines. This relieves inflammatory responses and improves the prognosis of patients with experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, pancreatitis, arthritis and other inflammatory syndromes. However, whether the cholinergic anti-inflammatory pathway has an effect on acute viral myocarditis has not been investigated. Here, we studied the effects of the cholinergic anti-inflammatory pathway on acute viral myocarditis.In a coxsackievirus B3 murine myocarditis model (Balb/c, nicotine and methyllycaconitine were used to stimulate and block the cholinergic anti-inflammatory pathway, respectively. Relevant signal pathways were studied to compare their effects on myocarditis, survival rate, histopathological changes, ultrastructural changes, and cytokine levels. Nicotine treatments significantly improved survival rate, attenuated myocardial lesions, and downregulated the expression of TNF-α and IL-6. Methyllycaconitine decreased survival rate, aggravated myocardial lesions, and upregulated the expression of TNF-α and IL-6. In addition, levels of the signaling protein phosphorylated STAT3 were higher in the nicotine group and lower in the methyllycaconitine group compared with the untreated myocarditis group.These results show that nicotine protects mice from CVB3-induced viral myocarditis and that methyllycaconitine aggravates viral myocarditis in mice. Because nicotine is a α7nAchR agonist and methyllycaconitine is a α7nAchR antagonist, we conclude that α7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-α and IL-6, and, ultimately, alleviates viral myocarditis. We also conclude that blocking α7nAchR reduces the phosphorylation of STAT3, increases the expression of TNF-α and IL-6, aggravating viral

  19. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior

    OpenAIRE

    Picciotto, Marina R.; Higley, Michael J.; Mineur, Yann S.

    2012-01-01

    Acetylcholine in the brain alters neuronal excitability, influences synaptic transmission, induces synaptic plasticity and coordinates the firing of groups of neurons. As a result, it changes the state of neuronal networks throughout the brain and modifies their response to internal and external inputs: the classical role of a neuromodulator. Here we identify actions of cholinergic signaling on cellular and synaptic properties of neurons in several brain areas and discuss the consequences of ...

  20. Attention, prediction and sequence learning : roles of the cholinergic basal forebrain and the retrosplenial cortex

    OpenAIRE

    Córdova, Christopher Andy

    2005-01-01

    Our ability to foresee and shape biologically important events relies on a combination of visuospatial attention, memory capacities, and an ability to learn new sequences of goal-directed action. A novel set of behavioral studies were conducted to investigate neurobiological processes that underlie selective attention and visuospatial sequence learning. The first experiment assessed a theorized computational role of basal forebrain cholinergic neurons in modulating attention by increasing sti...

  1. Novel Fast Adapting Interneurons Mediate Cholinergic-Induced Fast GABAA IPSCs In Striatal Spiny Neurons

    OpenAIRE

    Faust, Thomas W.; Assous, Maxime; Shah, Fulva; Tepper, James M.; Koós, Tibor

    2015-01-01

    Previous work suggests that neostriatal cholinergic interneurons control the activity of several classes of GABAergic interneurons through fast nicotinic receptor mediated synaptic inputs. Although indirect evidence has suggested the existence of several classes of interneurons controlled by this mechanism only one such cell type, the neuropeptide-Y expressing neurogliaform neuron, has been identified to date. Here we tested the hypothesis that in addition to the neurogliaform neurons that el...

  2. Acetylcholinesterase loosens the brain's cholinergic anti-inflammatory response and promotes epileptogenesis

    Directory of Open Access Journals (Sweden)

    Yehudit eGnatek

    2012-05-01

    Full Text Available Recent studies show a key role of brain inflammation in epilepsy. However, the mechanisms controlling brain immune response are only partly understood. In the periphery, acetylcholine (ACh release by the vagus nerve restrains inflammation by inhibiting the activation of leukocytes. Recent reports suggested a similar anti-inflammatory effect for ACh in the brain. Since brain cholinergic dysfunction are documented in epileptic animals, we explored changes in brain cholinergic gene expression and associated immune response during pilocarpine-induced epileptogenesis. Levels of acetylcholinesterase (AChE and inflammatory markers were measured using real-time RT-PCR, in-situ hybridization and immunostaining in wild type (WT and transgenic mice over-expressing the "synaptic" splice variant AChE-S (TgS. One month following pilocarpine, mice were video-monitored for spontaneous seizures. To test directly the effect of ACh on the brain's innate immune response, cytokines expression levels were measured in acute brain slices treated with cholinergic agents. We report a robust upregulation of AChE as early as 48 hrs following pilocarpine-induced status epilepticus (SE. AChE was expressed in hippocampal neurons, microglia and endothelial cells but rarely in astrocytes. TgS mice overexpressing AChE showed constitutive increased microglial activation, elevated levels of pro-inflammatory cytokines 48 hrs after SE and accelerated epileptogenesis compared to their WT counterparts. Finally we show a direct, muscarine-receptor dependant, nicotine-receptor independent anti-inflammatory effect of ACh in brain slices maintained ex vivo. Our work demonstrates for the first time, that ACh directly suppresses brain innate immune response and that AChE up-regulation after SE is associated with enhanced immune response, facilitating the epileptogenic process. Our results highlight the cholinergic system as a potential new target for the prevention of seizures and epilepsy.

  3. Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission

    Directory of Open Access Journals (Sweden)

    C.M. Queiroz

    2013-01-01

    Full Text Available Impaired cholinergic neurotransmission can affect memory formation and influence sleep-wake cycles (SWC. In the present study, we describe the SWC in mice with a deficient vesicular acetylcholine transporter (VAChT system, previously characterized as presenting reduced acetylcholine release and cognitive and behavioral dysfunctions. Continuous, chronic ECoG and EMG recordings were used to evaluate the SWC pattern during light and dark phases in VAChT knockdown heterozygous (VAChT-KDHET, n=7 and wild-type (WT, n=7 mice. SWC were evaluated for sleep efficiency, total amount and mean duration of slow-wave, intermediate and paradoxical sleep, as well as the number of awakenings from sleep. After recording SWC, contextual fear-conditioning tests were used as an acetylcholine-dependent learning paradigm. The results showed that sleep efficiency in VAChT-KDHET animals was similar to that of WT mice, but that the SWC was more fragmented. Fragmentation was characterized by an increase in the number of awakenings, mainly during intermediate sleep. VAChT-KDHET animals performed poorly in the contextual fear-conditioning paradigm (mean freezing time: 34.4±3.1 and 44.5±3.3 s for WT and VAChT-KDHET animals, respectively, which was followed by a 45% reduction in the number of paradoxical sleep episodes after the training session. Taken together, the results show that reduced cholinergic transmission led to sleep fragmentation and learning impairment. We discuss the results on the basis of cholinergic plasticity and its relevance to sleep homeostasis. We suggest that VAChT-KDHET mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders.

  4. Neuro-immune interactions via the cholinergic anti-inflammatory pathway

    OpenAIRE

    Gallowitsch-Puerta, Margot; Pavlov, Valentin A.

    2007-01-01

    The overproduction of TNF and other cytokines can cause the pathophysiology of numerous diseases. Controlling cytokine synthesis and release is critical for preventing unrestrained inflammation and maintaining health. Recent studies identified an efferent vagus nerve-based mechanism termed “the cholinergic anti-inflammatory pathway” that controls cytokine production and inflammation. Here we review current advances related to the role of this pathway in neuro-immune interactions that prevent ...

  5. Nerve growth factor protects cholinergic neurons against quinolinic acid-induced excitotoxicity in wistar rats

    OpenAIRE

    Vasiljević Ivana D.; Jovanović Marina D.; Čolić Miodrag J.; Mićić D.; Ninković Milica; Maličević Živorad

    2004-01-01

    The etiology of neuronal death in neurodegenerative diseases, including Huntington's disease (HD) is still unknown. There could be a complex interplay between altered energy metabolism, excitotoxicity and oxidative stress. Excitotoxic striatal lesions induced by quinolinic acid (QA), were used to test for the neuroprotective actions of nerve growth factor (NGF) on striatal cholinergic and GABAergic neurons. QA is an endogenous excitotoxin acting on N-methyl-D-aspartate (NMDA) rec...

  6. Impairment of reward-related learning by cholinergic cell ablation in the striatum

    OpenAIRE

    Kitabatake, Yasuji; Hikida, Takatoshi; Watanabe, Dai; Pastan, Ira; Nakanishi, Shigetada

    2003-01-01

    The striatum in the basal ganglia-thalamocortical circuitry is a key neural substrate that is implicated in motor balance and procedural learning. The projection neurons in the striatum are dynamically modulated by nigrostriatal dopaminergic input and intrastriatal cholinergic input. The role of intrastriatal acetylcholine (ACh) in learning behaviors, however, remains to be fully clarified. In this investigation, we examine the involvement of intrastriatal ACh in different categories of...

  7. Carbachol can be released at a cholinergic ganglionic synapse as a false transmitter.

    OpenAIRE

    Baux, G; Tauc, L

    1983-01-01

    Carbachol was injected into a presynaptic cholinergic neuron in the buccal ganglion of Aplysia and the quantal aspects of the Cl- -dependent postsynaptic response to a prolonged stimulation were analyzed by a statistical fluctuation method. The calculated amplitude of the miniature postsynaptic current was increased with respect to control. Statistical fluctuation analysis was also used to analyze the postsynaptic response obtained during ionophoretic application of acetylcholine and carbacho...

  8. Presynaptic transmitter content controls the number of quanta released at a neuro-neuronal cholinergic synapse.

    OpenAIRE

    Poulain, B; Baux, G; Tauc, L

    1986-01-01

    In the buccal ganglion of Aplysia the overloading of the cholinergic presynaptic neuron by exogenous acetylcholine (AcCho) led to an enhancement of the postsynaptic response. The deprivation of choline in the presynaptic neuron by extra- and/or intracellularly applied choline oxidase to prevent AcCho synthesis resulted in a decrease of the postsynaptic response. In both cases, the size of the calculated miniature postsynaptic current (i.e., the size of the quantum) remained unchanged. It was ...

  9. Cholinergic Dysfunction in Fragile X Syndrome and Potential Intervention: A Preliminary 1H MRS Study

    OpenAIRE

    Kesler, Shelli R.; Lightbody, Amy A.; Reiss, Allan L.

    2009-01-01

    Males with fragile X syndrome are at risk for significant cognitive and behavioral deficits, particularly those involving executive prefrontal systems. Disruption of the cholinergic system secondary to fragile X mental retardation protein deficiency may contribute to the cognitive-behavioral impairments associated with fragile X. We measured choline in the dorsolateral prefrontal cortex of 9 males with fragile X syndrome and 9 age-matched typically developing controls using 1H magnetic resona...

  10. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    International Nuclear Information System (INIS)

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  11. Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis.

    Directory of Open Access Journals (Sweden)

    Yaakov A Levine

    Full Text Available INTRODUCTION: The inflammatory reflex is a physiological mechanism through which the nervous system maintains immunologic homeostasis by modulating innate and adaptive immunity. We postulated that the reflex might be harnessed therapeutically to reduce pathological levels of inflammation in rheumatoid arthritis by activating its prototypical efferent arm, termed the cholinergic anti-inflammatory pathway. To explore this, we determined whether electrical neurostimulation of the cholinergic anti-inflammatory pathway reduced disease severity in the collagen-induced arthritis model. METHODS: Rats implanted with vagus nerve cuff electrodes had collagen-induced arthritis induced and were followed for 15 days. Animals underwent active or sham electrical stimulation once daily from day 9 through the conclusion of the study. Joint swelling, histology, and levels of cytokines and bone metabolism mediators were assessed. RESULTS: Compared with sham treatment, active neurostimulation of the cholinergic anti-inflammatory pathway resulted in a 52% reduction in ankle diameter (p = 0.02, a 57% reduction in ankle diameter (area under curve; p = 0.02 and 46% reduction overall histological arthritis score (p = 0.01 with significant improvements in inflammation, pannus formation, cartilage destruction, and bone erosion (p = 0.02, accompanied by numerical reductions in systemic cytokine levels, not reaching statistical significance. Bone erosion improvement was associated with a decrease in serum levels of receptor activator of NF-κB ligand (RANKL from 132±13 to 6±2 pg/mL (mean±SEM, p = 0.01. CONCLUSIONS: The severity of collagen-induced arthritis is reduced by neurostimulation of the cholinergic anti-inflammatory pathway delivered using an implanted electrical vagus nerve stimulation cuff electrode, and supports the rationale for testing this approach in human inflammatory disorders.

  12. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  13. Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model

    OpenAIRE

    Lockrow, Jason; Prakasam, Annamalai; Huang, Peng; Bimonte-Nelson, Heather; Sambamurti, Kumar; Granholm, Ann-Charlotte

    2008-01-01

    Down syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain. These deficits are replicated in the Ts65Dn mouse, which contains a partial trisomy of murine chromosome 16, the orthologous genetic segment to human chromosome 21. Oxidative stress levels are elevated early in DS, and may contribute to the neurodegeneration seen in these individuals. We evaluated ...

  14. Cholinergic properties of neurons differentiated from an embryonal carcinoma cell-line (P19).

    Science.gov (United States)

    Parnas, D; Linial, M

    1995-11-01

    P19 is a mouse-derived embryonal carcinoma cell-line capable of differentiation toward ectodermal, mesodermal and endodermal lineages. Following treatment with retinoic acid these cells differentiate into neurons, astrocytes and fibroblast-like cells. We induced P19 differentiation under conditions which lead to a homogeneous neuronal culture (> 95% neurons). Under these conditions, most cells (approximately 85%) express high levels of the cholinergic markers acetyl cholinesterase and choline acetyltransferase while approximately 10% of cells express the GABAergic marker glutamic acid decarboxylase. While the proportion of the GABAergic neurons is constant at different culture conditions, the cholinergic phenotype is suppressed at high cell densities. The cholinergic nature of P19 neurons is also evident in their ability to form contacts with a muscle cell-line--C2. At day 10 of differentiation cells are capable of depolarization-dependent acetylcholine release. The release is Ca2+ dependent, and drops to baseline levels at 0.5 mM Ca2+. The cells also respond to sub-nM levels of alpha-latrotoxin by acetylcholine release. All major proteins implicated in synapse functionality are expressed prior to day 10 at both at RNA and protein levels. However, the expression pattern of each gene is unique. The genes include cytoskeletal proteins, synaptic vesicle proteins and terminal specific proteins. We suggest that this cell-line can serve as an in-vitro model system for the study of neuronal phenotype acquisition. Under our conditions, the P19 cells can also provide a system in which to study the differentiation of functional cholinergic neurons. PMID:8787867

  15. Novel information on the non-neuronal cholinergic system in orthopedics provides new possible treatment strategies for inflammatory and degenerative diseases

    Directory of Open Access Journals (Sweden)

    Sture Forsgren

    2009-07-01

    Full Text Available Anti-cholinergic agents are used in the treatment of several pathological conditions. Therapy regimens aimed at up-regulating cholinergic functions, such as treatment with acetylcholinesterase inhibitors, are also currently prescribed. It is now known that not only is there a neuronal cholinergic system but also a non-neuronal cholinergic system in various parts of the body. Therefore, interference with the effects of acetylcholine (ACh brought about by the local production and release of ACh should also be considered. Locally produced ACh may have proliferative, angiogenic, wound-healing, and immunomodulatory functions. Interestingly, cholinergic stimulation may lead to anti-inflammatory effects. Within this review, new findings for the locomotor system of a more widespread non-neuronal cholinergic system than previously expected will be discussed in relation to possible new treatment strategies. The conditions discussed are painful and degenerative tendon disease (tendinopathy/tendinosis, rheumatoid arthritis, and osteoarthritis.

  16. Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin self-administration or conditioned place preference in rats.

    Directory of Open Access Journals (Sweden)

    Stephan Steidl

    Full Text Available Cholinergic input to the ventral tegmental area (VTA is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII, the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (±0.65% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin.

  17. [Bowel obstruction-induced cholinergic crisis with progressive respiratory failure following distigmine bromide treatment].

    Science.gov (United States)

    Kobayashi, Kazuki; Sekiguchi, Hiroshi; Sato, Nobuhiro; Hirose, Yasuo

    2016-03-01

    A 54-year-old female experienced rapid respiratory failure while being transported in an ambulance to our emergency department for evaluation and management of constipation and abdominal pain. The patient was on treatment with distigmine bromide for postoperative urination disorder and magnesium oxide for constipation. Increased salivary secretions, diminished respiratory excursion, type 2 respiratory failure (PaCO2 : 65 mmHg), low serum cholinesterase, and hypermagnesemia were detected. Imaging studies revealed that the patient had bilateral aspiration pneumonia, fecal impaction in the rectum, and a distended colon causing ileus. The patient was mechanically ventilated and was weaned off the ventilator on day 3. Therapeutic drug monitoring after discharge revealed that the serum level of distigmine bromide on admission was markedly elevated (377.8 ng/mL vs. the normal therapeutic level of 5-10 ng/mL). Distigmine bromide induced a cholinergic crisis with a resultant increase in airway secretions and respiratory failure. In this particular case, orally administered distigmine bromide was excessively absorbed because of prolonged intestinal transit time secondary to fecal impaction and sluggish bowel movement; this caused a cholinergic crisis and hypermagnesemia contributing to respiratory failure. Clinicians should be aware that bowel obstruction in a patient treated with distigmine bromide can increase the risk of a cholinergic crisis. PMID:27255021

  18. Effects of diazinon on the lymphocytic cholinergic system of Nile tilapia fish (Oreochromis niloticus).

    Science.gov (United States)

    Toledo-Ibarra, G A; Díaz-Resendiz, K J G; Pavón-Romero, L; Rojas-García, A E; Medina-Díaz, I M; Girón-Pérez, M I

    2016-08-01

    Fish rearing under intensive farming conditions can be easily disturbed by pesticides, substances that have immunotoxic properties and may predispose to infections. Organophosphorus pesticides (OPs) are widely used in agricultural activities; however, the mechanism of immunotoxicity of these substances is unclear. The aim of this study was to evaluate the effect of diazinon pesticides (OPs) on the cholinergic system of immune cells as a possible target of OP immunotoxicity. We evaluated ACh levels and cholinergic (nicotinic and muscarinic) receptor concentration. Additionally, AChE activity was evaluated in mononuclear cells of Nile tilapia (Oreochromis niloticus), a freshwater fish mostly cultivated in tropical regions around the world. The obtained results indicate that acute exposure to diazinon induces an increase in ACh concentration and a decrease in nAChR and mAChR concentrations and AChE activity in fish immune cells, This suggests that the non-neuronal lymphocytic cholinergic system may be the main target in the mechanism of OP immunotoxicity. This study contributes to the understanding of the mechanisms of immunotoxicity of pollutants and may help to take actions for animal health improvement. PMID:27260186

  19. Somatostatin inhibits cANP-mediated cholinergic transmission in the myenteric plexus

    International Nuclear Information System (INIS)

    The mechanism by which somatostatin acts to modulate cholinergic transmission is not clear. In this study the authors investigated the role of the adenosine 3',5'-cyclic monophosphate (cAMP) system in mediating cholinergic transmission in the guinea pig myenteric plexus and examined the ability of somatostatin to alter acetylcholine (ACh) release stimulated by various cAMP agonists. Forskolin, 8-bromo-cAMP, vasoactive intestinal peptide (VIP), and cholera toxin each stimulated the release of [3H]ACh in a dose-related manner. Addition of theophylline enhanced the release of [3H]ACh stimulated by these cAMP agonists. The observations suggest that cAMP may serve as a physiological mediator for ACh release from myenteric neurons. Somatostatin inhibited release of [3H]ACh evoked by various cAMP agonists in a dose-related manner. Pretreatment with pertussis toxin antagonized the inhibitory effect of somatostatin on the release of [3H]ACh evoked by forskolin, VIP, or cholera toxin but had no effect on the inhibitory action of somatostatin on the release of [3H]ACh evoked by 8-bromo-cAMP. This suggests that the principal mechanism by which somatostatin inhibits cAMP-mediated cholinergic transmission is via activation of the inhibitory regulatory protein (Ni subunit) of adenyalte cyclase

  20. Agricultural nitrate monitoring in a lake basin in Central Italy: a further step ahead towards an integrated nutrient management aimed at controlling water pollution.

    Science.gov (United States)

    Garnier, Monica; Recanatesi, Fabio; Ripa, Maria Nicoletta; Leone, Antonio

    2010-11-01

    Water pollution from point sources has been considerably reduced over the last few decades. Nevertheless, some water quality problems remain, which can be attributed to non-point pollution sources, and in particular to agriculture. In this paper the results of a study intended to assess the consequences, in terms of NO3 water pollution, of growing a crop, whose impact in terms of P pollution is already well known, are presented. The potential consequences, in terms of water pollution from nitrates of a BMP expressly applied to reduce P pollution are also discussed. The study site is the Lake Vico basin, Central Italy, which has suffered a shift in trophic state since the mid 1990s, caused by P compounds used for intensive cultivation of hazelnut trees. The results of the monitoring campaign described in this paper allow to assert that hazelnut tree cropping has probably caused a considerable increase in nitrate concentration in the groundwater, although not in the lake water, because of the specific hydrogeological characteristics of the basin. The main conclusion is that monitoring is essential to single out environmental characteristics peculiar of a specific area, which even the most sophisticated model would not have been able to highlight. This is why monitoring and model simulations should be integrated. PMID:19911291

  1. A sero-survey of rinderpest in nomadic pastoral systems in central and southern Somalia from 2002 to 2003, using a spatially integrated random sampling approach.

    Science.gov (United States)

    Tempia, S; Salman, M D; Keefe, T; Morley, P; Freier, J E; DeMartini, J C; Wamwayi, H M; Njeumi, F; Soumaré, B; Abdi, A M

    2010-12-01

    A cross-sectional sero-survey, using a two-stage cluster sampling design, was conducted between 2002 and 2003 in ten administrative regions of central and southern Somalia, to estimate the seroprevalence and geographic distribution of rinderpest (RP) in the study area, as well as to identify potential risk factors for the observed seroprevalence distribution. The study was also used to test the feasibility of the spatially integrated investigation technique in nomadic and semi-nomadic pastoral systems. In the absence of a systematic list of livestock holdings, the primary sampling units were selected by generating random map coordinates. A total of 9,216 serum samples were collected from cattle aged 12 to 36 months at 562 sampling sites. Two apparent clusters of RP seroprevalence were detected. Four potential risk factors associated with the observed seroprevalence were identified: the mobility of cattle herds, the cattle population density, the proximity of cattle herds to cattle trade routes and cattle herd size. Risk maps were then generated to assist in designing more targeted surveillance strategies. The observed seroprevalence in these areas declined over time. In subsequent years, similar seroprevalence studies in neighbouring areas of Kenya and Ethiopia also showed a very low seroprevalence of RP or the absence of antibodies against RP. The progressive decline in RP antibody prevalence is consistent with virus extinction. Verification of freedom from RP infection in the Somali ecosystem is currently in progress.

  2. Mathematical Verification for Transmission Performance of Centralized Lightwave WDM-RoF-PON with Quintuple Services Integrated in Each Wavelength Channel

    Directory of Open Access Journals (Sweden)

    Shuai Chen

    2015-01-01

    Full Text Available Wavelength-division-multiplexing passive-optical-network (WDM-PON has been recognized as a promising solution of the “last mile” access as well as multibroadband data services access for end users, and WDM-RoF-PON, which employs radio-over-fiber (RoF technique in WDM-PON, is even a more attractive approach for future broadband fiber and wireless access for its strong availability of centralized multiservices transmission operation and its transparency for bandwidth and signal modulation formats. As for multiservices development in WDM-RoF-PON, various system designs have been reported and verified via simulation or experiment till now, and the scheme with multiservices transmitted in each single wavelength channel is believed as the one that has the highest bandwidth efficiency; however, the corresponding mathematical verification is still hard to be found in state-of-the-art literature. In this paper, system design and data transmission performance of a quintuple services integrated WDM-RoF-PON which jointly employs carrier multiplexing and orthogonal modulation techniques, have been theoretically analyzed and verified in detail; moreover, the system design has been duplicated and verified experimentally and the theory system of such WDM-RoF-PON scheme has thus been formed.

  3. Development and Beam-Shape Analysis of an Integrated Fiber-Optic Confocal Probe for High-Precision Central Thickness Measurement of Small-Radius Lenses

    Directory of Open Access Journals (Sweden)

    Boonsong Sutapun

    2015-04-01

    Full Text Available This work describes a new design of a fiber-optic confocal probe suitable for measuring the central thicknesses of small-radius optical lenses or similar objects. The proposed confocal probe utilizes an integrated camera that functions as a shape-encoded position-sensing device. The confocal signal for thickness measurement and beam-shape data for off-axis measurement can be simultaneously acquired using the proposed probe. Placing the probe’s focal point off-center relative to a sample’s vertex produces a non-circular image at the camera’s image plane that closely resembles an ellipse for small displacements. We were able to precisely position the confocal probe’s focal point relative to the vertex point of a ball lens with a radius of 2.5 mm, with a lateral resolution of 1.2 µm. The reflected beam shape based on partial blocking by an aperture was analyzed and verified experimentally. The proposed confocal probe offers a low-cost, high-precision technique, an alternative to a high-cost three-dimensional surface profiler, for tight quality control of small optical lenses during the manufacturing process.

  4. From national to regional plans – the Integrated Drought Management Programme of the Global Water Partnership for Central and Eastern Europe

    Directory of Open Access Journals (Sweden)

    Sabina Bokal

    2014-06-01

    Full Text Available In the past few decades it has become evident that the countries of Central and Eastern Europe (CEE are affected by droughts which are becoming more and more lasting and severe. The region׳s vulnerability to this natural hazard alerted the public, governments, and operational agencies to the many socio-economic problems accompanying water shortage and to the need for drought mitigation measures. In addition, climate change amplifies the frequency and severity of droughts in the region. In this context, the CEE region of the Global Water Partnership (GWP recently launched the regional Integrated Drought Management Programme (IDMP as part of the global joint World Meteorological Organization (WMO/GWP IDMP. The purpose of this paper is to present the work plan of the GWP CEE IDM Programme which is being implemented in the years 2013–2015. The planning process for this Programme carried out in 2012 included national and regional reviews of existing drought risks, policies and strategies. The programme inception phase was summarized in October 2012 by a regional workshop organized jointly by GWP and WMO, with the participation of representatives of the United Nations Convention to Combat Desertification (UNCCD Secretariat, the Drought Management Centre for Southeastern Europe (DMCSEE, the EU Joint Research Centre, the United Nations Economic Commission for Europe (UNECE and the European Drought Centre. The Programme was launched in February 2013 and involves more than 40 organizations from 9 CEE countries. The basic four elements of the Programme include policy advice, demonstration projects, capacity building knowledge management and regional cooperation (from national to regional plans. The major output, building upon national initiatives, shall be a coordinated regional framework for drought monitoring, early warning, prediction and management, accompanied by a set of guidelines and tools for the development of regional, national and local

  5. A novel educational strategy targeting health care workers in underserved communities in Central America to integrate HIV into primary medical care.

    Directory of Open Access Journals (Sweden)

    Tamara Flys

    Full Text Available BACKGROUND: Current educational strategies to integrate HIV care into primary medical care in Central America have traditionally targeted managers or higher-level officials, rather than local health care workers (HCWs. We developed a complementary online and on-site interactive training program to reach local HCWs at the primary care level in underserved communities. METHODS: The training program targeted physicians, nurses, and community HCWs with limited access to traditional onsite training in Panama, Nicaragua, Dominican Republic, and Guatemala. The curriculum focused on principles of HIV care and health systems using a tutor-supported blended educational approach of an 8-week online component, a weeklong on-site problem-solving workshop, and individualized project-based interventions. RESULTS: Of 258 initially active participants, 225 (225/258=87.2% successfully completed the online component and the top 200 were invited to the on-site workshop. Of those, 170 (170/200=85% attended the on-site workshop. In total, 142 completed all three components, including the project phase. Quantitative and qualitative evaluation instruments included knowledge assessments, reflexive essays, and acceptability surveys. The mean pre and post-essay scores demonstrating understanding of social determinants, health system organization, and integration of HIV services were 70% and 87.5%, respectively, with an increase in knowledge of 17.2% (p<0.001. The mean pre- and post-test scores evaluating clinical knowledge were 70.9% and 90.3%, respectively, with an increase in knowledge of 19.4% (p<0.001. A survey of Likert scale and open-ended questions demonstrated overwhelming participant satisfaction with course content, structure, and effectiveness in improving their HIV-related knowledge and skills. CONCLUSION: This innovative curriculum utilized technology to target HCWs with limited access to educational resources. Participants benefited from technical skills

  6. Non-adrenergic non-cholinergic (NANC) excitatory response of the channel catfish intestine.

    Science.gov (United States)

    Venugopalan, C S; Holmes, E P; Jarboe, H H; Kleinow, K M

    1994-06-01

    1. Optimal parameters for electrical field stimulation (EFS) of catfish pyloric and middle intestinal segments were determined (15 Hz, 60 V) from a range of frequencies (5-45 Hz) and voltages (40-120 V) using a modified Magnus' method. Contractile responses were produced by EFS which were reproducible and showed no significant difference between the tissues. 2. The contractile cholinergic responses of the tissues to carbachol and acetylcholine (ACh) were blocked by atropine on an equimolar concentration, whereas, these responses were enhanced in the presence of neostigmine, and acetylcholinesterase inhibitor. 3. Adrenergic responses were examined with noradrenaline (NA). NA produced contraction of the segments only, at a concentration of 10(-4) M. Among the various adrenoceptors, beta-adrenoceptor stimulation produced a weak relaxation whereas, both alpha 1- and alpha 2-adrenoceptor stimulation produced contractions, of which alpha 2-induced contraction was of greater magnitude. The beta, alpha 1 and alpha 2 responses were blocked by their respective blocking agents propranolol, prazosin and yohimbine. 4. The autonomic components of the response to EFS were determined by using selected cholinergic and adrenergic antagonists separately or collectively. Cholinergic blockade with atropine did not produce a significant blockade of the EFS-induced response. Similarly, blockade of beta-adrenoceptors with propranolol did not modulate the contractile response to EFS to any significant level. Blockade by prazosin or yohimbine did not significantly change the contractile response to EFS. After a complete blockade of the adrenergic and cholinergic divisions, the intestinal segments still showed a contractile response to EFS which was not significantly different from the control response. This indicated the presence of a non-adrenergic non-cholinergic (NANC) response. 5. Tetrodotoxin, at 10(-6) M, significantly blocked the EFS-induced NANC response suggesting a neurogenic

  7. Cholinergic Stimulation Prevents the Development of Autoimmune Diabetes: Evidence for the Modulation of Th17 Effector Cells via an IFNγ-Dependent Mechanism

    Science.gov (United States)

    George, Junu A.; Bashir, Ghada; Qureshi, Mohammed M.; Mohamed, Yassir A.; Azzi, Jamil; al-Ramadi, Basel K.; Fernández-Cabezudo, Maria J.

    2016-01-01

    Type I diabetes (T1D) results from T cell-mediated damage of pancreatic β-cells and loss of insulin production. The cholinergic anti-inflammatory pathway represents a physiological link connecting the central nervous and immune systems via vagus nerve, and functions to control the release of proinflammatory cytokines. Using the multiple low-dose streptozotocin (MLD-STZ) model to induce experimental autoimmune diabetes, we investigated the potential of regulating the development of hyperglycemia through administration of paraoxon, a highly specific acetylcholinesterase inhibitor (AChEI). We demonstrate that pretreatment with paraoxon prevented hyperglycemia in STZ-treated C57BL/6 mice. This correlated with a reduction in T cell infiltration into pancreatic islets and preservation of the structure and functionality of β-cells. Gene expression analysis of pancreatic tissue revealed that increased peripheral cholinergic activity prevented STZ-mediated loss of insulin production, this being associated with a reduction in IL-1β, IL-6, and IL-17 proinflammatory cytokines. Intracellular cytokine analysis in splenic T cells demonstrated that inhibition of AChE led to a shift in STZ-induced immune response from a predominantly disease-causing IL-17-expressing Th17 cells to IFNγ-positive Th1 cells. Consistent with this conclusion, inhibition of AChE failed to prevent STZ-induced hyperglycemia in IFNγ-deficient mice. Our results provide mechanistic evidence for the prevention of murine T1D by inhibition of AChE and suggest a promising strategy for modulating disease severity. PMID:27790217

  8. Integrated seismic model of the crust and upper mantle of the Trans-European Suture zone between the Precambrian craton and Phanerozoic terranes in Central Europe

    Science.gov (United States)

    Wilde-Piórko, Monika; Świeczak, Marzena; Grad, Marek; Majdański, Mariusz

    2010-01-01

    The structure and evolution of the Trans-European Suture zone (TESZ), contact between Precambrian Europe to the northeast and Phanerozoic terranes to the southwest is one of the main tectonic questions in Europe. The knowledge of the crustal structure, lithosphere-asthenosphere boundary and mantle transition zone between two seismic discontinuities at depths "410" and "660" km, is one of the most important issues to understand the Earth's dynamics. To create a mantle model of the TESZ and surroundings we used different seismic data collected along the 950 km long POLONAISE'97 profile P4. Previous results of 2-D ray-tracing and P-wave travel time modelling and new results of P-wave travel time residuals methods and receiver function sections provide facts about the seismic structure from the surface down to 900 km depth. In the TESZ a large basin, about 125 km wide, is filled with sedimentary strata (Vp 7.0 km s - 1 ) along most of the P4 profile. However, lower values to the southwest may indicate the termination of Baltica. High velocity (~ 8.35 km s - 1 ) uppermost mantle lies beneath the Avalonia/Variscan terranes, and may be due to rifting and/or subduction. The seismic lithosphere thickness for the EEC is about 200 km, while it is only 90 km in the Palaeozoic platform (PP). The mantle transition zone is shallower and about 30 km thicker under the EEC, which could be due to thermal conditions (lower temperature) and/or the presence of water and FeO. The result of this paper is a new compiled and integrated seismic velocity model, available in digital form down to 900 km depth ( http://www.igf.fuw.edu.pl/p4-mantle), which can be used as a preliminary model of the crust and upper mantle in the TESZ area in Central Europe.

  9. Integrated Geohazard Screening Using Remote Sensing, Including Satellite and Helicopter Based Imagery, LiDAR, and Geophysics, in Tajikistan and Kyrgyzstan, Central Asia

    Science.gov (United States)

    Wade, A. M.; Kozaci, O.; Hitchcock, C. S.; Konieczny, G.; Garrie, D.

    2015-12-01

    We performed a detailed geohazard investigation of a 5 km-wide, 650km-long corridor through Tajikistan and Kyrgyzstan, Central Asia. The study area includes the Rasht and Alai valleys at the boundary between the Pamir Mountains and the Alai Range of the southern Tien Shan. Ongoing collision between the India and Eurasia plates has resulted in the Tien Shan orogenic belt and the Pamir Mountains. Thus the study area is one of the most seismically active regions in the world. Rapid uplift, erosion, and steep slopes give rise to widespread landsliding and massive rock slope failures in both the Pamir and Tien Shan Mountains. Our integrated data acquisition and interpretation plan used airborne and remote sensing methods including satellite based DEMs and high resolution imagery, LiDAR, aerial photography, and helicopter based electromagnetic resistivity (HEM). Analysis of these data sets allowed us to delineate potential geohazards through surficial geologic mapping. Initial desktop geohazard screening included 1:50,000-scale mapping for potential faults, landslides, and liquefiable deposits, which included traffic light-style susceptibility maps for route refinement and hazard mitigation. As part of detailed investigations, continuous HEM data was collected and processed at a spatial sampling interval of approximately 3m. Apparent resistivity was calculated for each of the five operating frequencies over the entire survey area. For the purposes of this study, resistivity values at 10 m and 20 m depths were sliced from the interpolated 3D Differential Resistivity model for use in the analysis. Using GIS, we compared these results with mapped Quaternary units and found good correlation between resistivity contrasts and the boundaries of mapped surficial units. With this confidence, the HEM measurements were further analyzed to identify subsurface features and to develop a 3D geologic model. Based on this analysis we provided a framework for an optimized geotechnical

  10. A credibility-based chance-constrained optimization model for integrated agricultural and water resources management: A case study in South Central China

    Science.gov (United States)

    Lu, Hongwei; Du, Peng; Chen, Yizhong; He, Li

    2016-06-01

    This study presents a credibility-based chance-constrained optimization model for integrated agricultural irrigation and water resources management. The model not only deals with parameter uncertainty represented as fuzzy sets, but also provides a credibility level which indicates the confidence level of the generated optimal management strategies. The model is used on a real-world case study in South Central China. Results from the case study reveal that: (1) a reduction in credibility level would result in an increasing planting area of watermelon, but impaired the planting acreage of high-quality rice and silk; (2) groundwater allocation would be prioritized for reducing surface water utilization cost; (3) the actual phosphorus and nitrogen emissions reached their limit values in most of the zones over the planning horizon (i.e., phosphorus and nitrogen emissions reaching 969 tonnes and 3814 tonnes under λ = 1.00, respectively; phosphorus and nitrogen emissions reaching 972 tonnes and 3891 tonnes under λ = 0.70, respectively). When the credibility level reduces from 1.00 to 0.70, system benefit would rise by 32.60% and groundwater consumption would be reduced by 79.51%. However, the pollutant discharge would not increase as expected, which would be reduced by 40.14% on the contrary. If system benefit is not of major concern, an aggressive strategy is suggested by selecting a rather low credibility level (say, 0.70). This strategy is suggested for guaranteeing protection of local groundwater resources and mitigation of local environmental deterioration by sacrificing part of system benefit.

  11. Mapping resource use over a Russian landscape: an integrated look at harvesting of a non-timber forest product in central Kamchatka

    International Nuclear Information System (INIS)

    Small-scale resource use became an important adaptive mechanism in remote logging communities in Russia at the onset of the post-Soviet period in 1991. We focused on harvesting of a non-timber forest product, lingonberry (Vaccinium vitis-idaea), in the forests of the Kamchatka Peninsula (Russian Far East). We employed an integrated geographical approach to make quantifiable connections between harvesting and the landscape, and to interpret these relationships in their broader contexts. Landsat TM images were used for a new classification; the resulting land-cover map was the basis for linking non-spatial data on harvesters’ gathering behaviors to spatial data within delineated lingonberry gathering sites. Several significant relationships emerged: (1) mature forests negatively affected harvesters’ initial choice to gather in a site, while young forests had a positive effect; (2) land-cover type was critical in determining how and why gathering occurred: post-disturbance young and maturing forests were significantly associated with higher gathering intensity and with the choice to market harvests; and (3) distance from gathering sites to villages and main roads also mattered: longer distances were significantly correlated to more time spent gathering and to increased marketing of harvests. We further considered our findings in light of the larger ecological and social dynamics at play in central Kamchatka. This unique study is an important starting point for conservation- and sustainable development-based work, and for additional research into the drivers of human–landscape interactions in the Russian Far East. (letter)

  12. Non-neuronal cardiac cholinergic system influences CNS via the vagus nerve to acquire a stress-refractory propensity.

    Science.gov (United States)

    Oikawa, Shino; Kai, Yuko; Tsuda, Masayuki; Ohata, Hisayuki; Mano, Asuka; Mizoguchi, Naoko; Sugama, Shuei; Nemoto, Takahiro; Suzuki, Kenji; Kurabayashi, Atsushi; Muramoto, Kazuyo; Kaneda, Makoto; Kakinuma, Yoshihiko

    2016-11-01

    We previously developed cardiac ventricle-specific choline acetyltransferase (ChAT) gene-overexpressing transgenic mice (ChAT tgm), i.e. an in vivo model of the cardiac non-neuronal acetylcholine (NNA) system or non-neuronal cardiac cholinergic system (NNCCS). By using this murine model, we determined that this system was responsible for characteristics of resistance to ischaemia, or hypoxia, via the modulation of cellular energy metabolism and angiogenesis. In line with our previous study, neuronal ChAT-immunoreactivity in the ChAT tgm brains was not altered from that in the wild-type (WT) mice brains; in contrast, the ChAT tgm hearts were the organs with the highest expression of the ChAT transgene. ChAT tgm showed specific traits in a central nervous system (CNS) phenotype, including decreased response to restraint stress, less depressive-like and anxiety-like behaviours and anti-convulsive effects, all of which may benefit the heart. These phenotypes, induced by the activation of cardiac NNCCS, were dependent on the vagus nerve, because vagus nerve stimulation (VS) in WT mice also evoked phenotypes similar to those of ChAT tgm, which display higher vagus nerve discharge frequency; in contrast, lateral vagotomy attenuated these traits in ChAT tgm to levels observed in WT mice. Furthermore, ChAT tgm induced several biomarkers of VS responsible for anti-convulsive and anti-depressive-like effects. These results suggest that the augmentation of the NNCCS transduces an effective and beneficial signal to the afferent pathway, which mimics VS. Therefore, the present study supports our hypothesis that activation of the NNCCS modifies CNS to a more stress-resistant state through vagus nerve activity. PMID:27528769

  13. Cholinergic modulation of Pavlovian fear conditioning in rats: differential effects of intrahippocampal infusion of mecamylamine and methyllycaconitine.

    Science.gov (United States)

    Vago, David R; Kesner, Raymond P

    2007-03-01

    The cholinergic system has consistently been implicated in Pavlovian fear conditioning. Considerable work has been done to localize specific nicotinic receptor subtypes in the hippocampus and determine their functional importance; however, the specific function of many of these subtypes has yet to be determined. An alpha7 nicotinic antagonist methyllycaconitine (MLA) (35 microg), and a broad spectrum non-alpha7 nicotinic antagonist mecamylamine (35 microg) was injected directly into the dorsal hippocampus or overlying cortex either 15 min pre-, 1 min post-, or 6h post-fear conditioning. One week after conditioning, retention of contextual and cue (tone) conditioning were assessed. A significant impairment in retention of contextual fear was observed when mecamylamine was injected 15 min pre- and 1 min post-conditioning. No significant impairment was observed when mecamylamine was injected 6h post-conditioning. Likewise, a significant impairment in retention of contextual fear was observed when MLA was injected 1 min post-conditioning; however, in contrast, MLA did not show any significant impairments when injected 15 min pre-conditioning, but did show a significant impairment when injected 6h post-conditioning. There were no significant impairments observed when either drug was injected into overlying cortex. No significant impairments were observed in cue conditioning for either drug. In general, specific temporal dynamics involved in nicotinic receptor function were found relative to time of receptor dysfunction. The results indicate that the greatest deficits in long-term retention (1 week) of contextual fear are produced by central infusion of MLA minutes to hours post-conditioning or mecamylamine within minutes of conditioning.

  14. Histaminergic modulation of cholinergic release from the nucleus basalis magnocellularis into insular cortex during taste aversive memory formation.

    Directory of Open Access Journals (Sweden)

    Liliana Purón-Sierra

    Full Text Available The ability of acetylcholine (ACh to alter specific functional properties of the cortex endows the cholinergic system with an important modulatory role in memory formation. For example, an increase in ACh release occurs during novel stimulus processing, indicating that ACh activity is critical during early stages of memory processing. During novel taste presentation, there is an increase in ACh release in the insular cortex (IC, a major structure for taste memory recognition. There is extensive evidence implicating the cholinergic efferents of the nucleus basalis magnocellularis (NBM in cortical activity changes during learning processes, and new evidence suggests that the histaminergic system may interact with the cholinergic system in important ways. However, there is little information as to whether changes in cholinergic activity in the IC are modulated during taste memory formation. Therefore, in the present study, we evaluated the influence of two histamine receptor subtypes, H1 in the NBM and H3 in the IC, on ACh release in the IC during conditioned taste aversion (CTA. Injection of the H3 receptor agonist R-α-methylhistamine (RAMH into the IC or of the H1 receptor antagonist pyrilamine into the NBM during CTA training impaired subsequent CTA memory, and simultaneously resulted in a reduction of ACh release in the IC. This study demonstrated that basal and cortical cholinergic pathways are finely tuned by histaminergic activity during CTA, since dual actions of histamine receptor subtypes on ACh modulation release each have a significant impact during taste memory formation.

  15. Decrease of a Current Mediated by Kv1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism

    Directory of Open Access Journals (Sweden)

    Cecilia Tubert

    2016-09-01

    Full Text Available The mechanism underlying a hypercholinergic state in Parkinson’s disease (PD remains uncertain. Here, we show that disruption of the Kv1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing Kv1.3 subunits contribute significantly to the orphan potassium current known as IsAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by Kv1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting Kv1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of Kv1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic interneurons, which were thought to be largely dependent on KCa channels.

  16. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    Science.gov (United States)

    Guzman, Monica S; De Jaeger, Xavier; Raulic, Sanda; Souza, Ivana A; Li, Alex X; Schmid, Susanne; Menon, Ravi S; Gainetdinov, Raul R; Caron, Marc G; Bartha, Robert; Prado, Vania F; Prado, Marco A M

    2011-11-01

    Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT) from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN) and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease. PMID:22087075

  17. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    Directory of Open Access Journals (Sweden)

    Monica S Guzman

    2011-11-01

    Full Text Available Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.

  18. Immunolocalization of choline acetyltransferase of common type in the central brain mass of Octopus vulgaris

    Directory of Open Access Journals (Sweden)

    A. Casini

    2012-07-01

    Full Text Available Acetylcholine, the first neurotransmitter to be identified in the vertebrate frog, is widely distributed among the animal kingdom. The presence of a large amount of acetylcholine in the nervous system of cephalopods is well known from several biochemical and physiological studies. However, little is known about the precise distribution of cholinergic structures due to a lack of a suitable histochemical technique for detecting acetylcholine. The most reliable method to visualize the cholinergic neurons is the immunohistochemical localization of the enzyme choline acetyltransferase, the synthetic enzyme of acetylcholine. Following our previous study on the distribution patterns of cholinergic neurons in the Octopus vulgaris visual system, using a novel antibody that recognizes choline acetyltransferase of the common type (cChAT, now we extend our investigation on the octopus central brain mass. When applied on sections of octopus central ganglia, immunoreactivity for cChAT was detected in cell bodies of all central brain mass lobes with the notable exception of the subfrontal and subvertical lobes. Positive varicosed nerves fibers where observed in the neuropil of all central brain mass lobes.

  19. Immunolocalization of choline acetyltransferase of common type in the central brain mass of Octopus vulgaris.

    Science.gov (United States)

    Casini, A; Vaccaro, R; D'Este, L; Sakaue, Y; Bellier, J P; Kimura, H; Renda, T G

    2012-07-19

    Acetylcholine, the first neurotransmitter to be identified in the vertebrate frog, is widely distributed among the animal kingdom. The presence of a large amount of acetylcholine in the nervous system of cephalopods is well known from several biochemical and physiological studies. However, little is known about the precise distribution of cholinergic structures due to a lack of a suitable histochemical technique for detecting acetylcholine. The most reliable method to visualize the cholinergic neurons is the immunohistochemical localization of the enzyme choline acetyltransferase, the synthetic enzyme of acetylcholine. Following our previous study on the distribution patterns of cholinergic neurons in the Octopus vulgaris visual system, using a novel antibody that recognizes choline acetyltransferase of the common type (cChAT), now we extend our investigation on the octopus central brain mass. When applied on sections of octopus central ganglia, immunoreactivity for cChAT was detected in cell bodies of all central brain mass lobes with the notable exception of the subfrontal and subvertical lobes. Positive varicosed nerves fibers where observed in the neuropil of all central brain mass lobes.

  20. In vivo PET imaging of brain nicotinic cholinergic receptors

    International Nuclear Information System (INIS)

    Neuronal acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system where they modulate a number of CNS functions including neurotransmitter release, cognitive function, anxiety, analgesia and control of cerebral blood flow. In the brain, a major subtype is composed of the α4β2 subunit combination. Density of this subtype has been shown to be decreased in patients with neuro-degenerative disease such as Alzheimer and Parkinson's disease (AD and PD), and mutated receptors has been described in some familial epilepsy. Thus, in vivo mapping of the nicotinic nAChRs by Positron Emission Tomography (PET) are of great interest to monitor the evolution of these pathologies and changes in the neuronal biochemistry induced by therapeutic agents. Recently, a new compound, 3-[2(S)-2-azetidinyl-methoxy]pyridine (A-85380) has been synthesised and labelled with fluorine-18, [18F]fluoro-A-85380 (Dolle et al., 1999). The [18F]fluoro-A-85380 has been shown to bind with high affinity t o nAChRs in vitro (Saba et al., 2004), and its toxicity was low and compatible with it s use at tracer dose in human PET studies (Valette, 2002). PET studies in baboons showed that, after in vivo administration of [ 18F]fluoro-A-85380 at a tracer dose, the distribution of the radioactivity in the brain reflect the distribution of the 18F]fluoro-A-8538 0 combined with its low toxicity make possible the imaging of the nicotinic receptor s in human by PET (Bottlaender 2003). Studies were performed in healthy non-smoker volunteers to evaluate the brain kinetics of [18F]fluoro-A-85380 and to assess the quantification of its nAChRs binding in the human brain with PET (Gallezot et a., 2005). The [18F]fluoro-A-85380 was also used in epileptic patients to whom a mutation in the α4 or β2 nAChRs subunit have been identified. We found that, in these patients, the pattern of the brain distribution of the radiotracer was found different when compared to the healthy subjects

  1. Effects of bone morphogenetic protein-4 on spatial memory and cholinergic expression in the dentate gyrus after fornix-fimbria transection in rats

    Institute of Scientific and Technical Information of China (English)

    Lei Liu; Yilong Xue; Jingkun Pan; Yazhuo Hu; Yuhong Gao; Yun Luo

    2008-01-01

    , Morris water maze test was performed in all rats to test spatial memory. Time-to-platform and swim-path length were recorded. Immunohistochemical staining of cholinergic neurons was performed on brain sections containing dentate gyrus. The area covered by ChAT-positive cells was analyzed using an Image-prog-plus image analysis software. MAIN OUTCOME MEASURES: Area covered by ChAT-positive cells in the dentate gyrus. Time-to-platform and swim path-length.RESULTS: Twenty-seven rats were included in the final analysis. In the Alzheimer's disease group, the area covered by ChAT-positive cells was significantly smaller compared with the normal control group (F = 76.03, P < 0.01). The area covered by ChAT-positive cells was significantly larger in the BMP-4- Alzheimer's disease group than in the model group (F = 35.17, P < 0.05), but significantly smaller than in the normal control group (F = 40.17, P < 0.05). Time-to-platform and swim-path length were significantly longer in the Alzheimer's disease group than in the normal control group (F =24.62 and 631.58, respectively, both P < 0.05). Time-to-platform and swim-path length were significantly shorter in the BMP4-Alzheimer's disease group compared with the model group (F = 22.06 and 606.89, respectively P < 0.05).CONCLUSION: Injection of BMP-4 into the dentate gyrus of Alzheimer's disease model rats alleviates central cholinergic system injury and concomitantly improves spatial memory.

  2. Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway.

    Directory of Open Access Journals (Sweden)

    Claude Sadis

    Full Text Available Kidney ischemia/reperfusion injury (I/R is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor of a variety of innate immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR. Herein, we tested the potential protective effect of nicotine administration in a mouse model of renal I/R injury induced by bilateral clamping of kidney arteries. Renal function, tubular damages and inflammatory response were compared between control animals and mice receiving nicotine at the time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the alpha7nAChR, as attested by the absence of protection in alpha7nAChR-deficient mice. Additionally, nicotine significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the CXC-chemokine KC, TNF-alpha and the proinflammatory high-mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice was associated with a decrease in tubular cell apoptosis and proliferative response as attested by the reduction of caspase-3 and Ki67 positive cells, respectively. All together, these data highlight that nicotine exerts a protective anti-inflammatory effect during kidney I/R through the cholinergic alpha7nAChR pathway. In addition, this could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation.

  3. Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning.

    Science.gov (United States)

    Brown, Matthew T C; Tan, Kelly R; O'Connor, Eoin C; Nikonenko, Irina; Muller, Dominique; Lüscher, Christian

    2012-12-20

    The ventral tegmental area (VTA) and nucleus accumbens (NAc) are essential for learning about environmental stimuli associated with motivationally relevant outcomes. The task of signalling such events, both rewarding and aversive, from the VTA to the NAc has largely been ascribed to dopamine neurons. The VTA also contains GABA (γ-aminobutyric acid)-releasing neurons, which provide local inhibition and also project to the NAc. However, the cellular targets and functional importance of this long-range inhibitory projection have not been ascertained. Here we show that GABA-releasing neurons of the VTA that project to the NAc (VTA GABA projection neurons) inhibit accumbal cholinergic interneurons (CINs) to enhance stimulus-outcome learning. Combining optogenetics with structural imaging and electrophysiology, we found that VTA GABA projection neurons selectively target NAc CINs, forming multiple symmetrical synaptic contacts that generated inhibitory postsynaptic currents. This is remarkable considering that CINs represent a very small population of all accumbal neurons, and provide the primary source of cholinergic tone in the NAc. Brief activation of this projection was sufficient to halt the spontaneous activity of NAc CINs, resembling the pause recorded in animals learning stimulus-outcome associations. Indeed, we found that forcing CINs to pause in behaving mice enhanced discrimination of a motivationally important stimulus that had been associated with an aversive outcome. Our results demonstrate that VTA GABA projection neurons, through their selective targeting of accumbal CINs, provide a novel route through which the VTA communicates saliency to the NAc. VTA GABA projection neurons thus emerge as orchestrators of dopaminergic and cholinergic modulation in the NAc.

  4. Measurement of the centrality and pseudorapidity dependence of the integrated elliptic flow in lead-lead collisions at $\\sqrt{s_{\\mathrm{NN}}}=2.76$ TeV with the ATLAS detector.

    CERN Document Server

    Aad, Georges; Abdallah, Jalal; Abdel Khalek, Samah; Abdinov, Ovsat; Aben, Rosemarie; Abi, Babak; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Abreu, Ricardo; Abulaiti, Yiming; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Adelman, Jahred; Adomeit, Stefanie; Adye, Tim; Agatonovic-Jovin, Tatjana; Aguilar-Saavedra, Juan Antonio; Agustoni, Marco; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albrand, Solveig; Alconada Verzini, Maria Josefina; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexandre, Gauthier; Alexopoulos, Theodoros; Alhroob, Muhammad; Alimonti, Gianluca; Alio, Lion; Alison, John; Allbrooke, Benedict; Allison, Lee John; Allport, Phillip; Allwood-Spiers, Sarah; Almond, John; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Altheimer, Andrew David; Alvarez Gonzalez, Barbara; Alviggi, Mariagrazia; Amako, Katsuya; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amorim, Antonio; Amoroso, Simone; Amram, Nir; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Anduaga, Xabier; Angelidakis, Stylianos; Angelozzi, Ivan; Anger, Philipp; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonaki, Ariadni; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Apolle, Rudi; Arabidze, Giorgi; Aracena, Ignacio; Arai, Yasuo; Araque, Juan Pedro; Arce, Ayana; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnal, Vanessa; Arnold, Hannah; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Ask, Stefan; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; Auerbach, Benjamin; Augsten, Kamil; Aurousseau, Mathieu; Avolio, Giuseppe; Azuelos, Georges; Azuma, Yuya; Baak, Max; Bacci, Cesare; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Backhaus, Malte; Backus Mayes, John; Badescu, Elisabeta; Bagiacchi, Paolo; Bagnaia, Paolo; Bai, Yu; Bain, Travis; Baines, John; Baker, Oliver Keith; Baker, Sarah; Balek, Petr; Balli, Fabrice; Banas, Elzbieta; Banerjee, Swagato; Bangert, Andrea Michelle; Bannoura, Arwa A E; Bansal, Vikas; Bansil, Hardeep Singh; Barak, Liron; Baranov, Sergei; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Barillari, Teresa; Barisonzi, Marcello; Barklow, Timothy; Barlow, Nick; Barnett, Bruce; Barnett, Michael; Barnovska, Zuzana; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Bartoldus, Rainer; Barton, Adam Edward; Bartos, Pavol; Bartsch, Valeria; Bassalat, Ahmed; Basye, Austin; Bates, Richard; Batkova, Lucia; Batley, Richard; Battistin, Michele; Bauer, Florian; Bawa, Harinder Singh; Beau, Tristan; Beauchemin, Pierre-Hugues; Beccherle, Roberto; Bechtle, Philip; Beck, Hans Peter; Becker, Anne Kathrin; Becker, Sebastian; Beckingham, Matthew; Becot, Cyril; Beddall, Andrew; Beddall, Ayda; Bedikian, Sourpouhi; Bednyakov, Vadim; Bee, Christopher; Beemster, Lars; Beermann, Thomas; Begel, Michael; Behr, Katharina; Belanger-Champagne, Camille; Bell, Paul; Bell, William; Bella, Gideon; Bellagamba, Lorenzo; Bellerive, Alain; Bellomo, Massimiliano; Belloni, Alberto; Belotskiy, Konstantin; Beltramello, Olga; Benary, Odette; Benchekroun, Driss; Bendtz, Katarina; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez Garcia, Jorge-Armando; Benjamin, Douglas; Bensinger, James; Benslama, Kamal; Bentvelsen, Stan; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Berghaus, Frank; Berglund, Elina; Beringer, Jürg; Bernard, Clare; Bernat, Pauline; Bernius, Catrin; Bernlochner, Florian Urs; Berry, Tracey; Berta, Peter; Bertella, Claudia; Bertolucci, Federico; Besana, Maria Ilaria; Besjes, Geert-Jan; Bessidskaia, Olga; Besson, Nathalie; Betancourt, Christopher; Bethke, Siegfried; Bhimji, Wahid; Bianchi, Riccardo-Maria; Bianchini, Louis; Bianco, Michele; Biebel, Otmar; Bieniek, Stephen Paul; Bierwagen, Katharina; Biesiada, Jed; Biglietti, Michela; Bilbao De Mendizabal, Javier; Bilokon, Halina; Bindi, Marcello; Binet, Sebastien; Bingul, Ahmet; Bini, Cesare; Black, Curtis; Black, James; Black, Kevin; Blackburn, Daniel; Blair, Robert; Blanchard, Jean-Baptiste; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blum, Walter; Blumenschein, Ulrike; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Boddy, Christopher Richard; Boehler, Michael; Boek, Jennifer; Boek, Thorsten Tobias; Bogaerts, Joannes Andreas; Bogdanchikov, Alexander; Bogouch, Andrei; Bohm, Christian; Bohm, Jan; Boisvert, Veronique; Bold, Tomasz; Boldea, Venera; Boldyrev, Alexey; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Borri, Marcello; Borroni, Sara; Bortfeldt, Jonathan; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Boterenbrood, Hendrik; Boudreau, Joseph; Bouffard, Julian; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Bousson, Nicolas; Boutouil, Sara; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozovic-Jelisavcic, Ivanka; Bracinik, Juraj; Branchini, Paolo; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Brazzale, Simone Federico; Brelier, Bertrand; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Richard; Bressler, Shikma; Bristow, Kieran; Bristow, Timothy Michael; Britton, Dave; Brochu, Frederic; Brock, Ian; Brock, Raymond; Bromberg, Carl; Bronner, Johanna; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brosamer, Jacquelyn; Brost, Elizabeth; Brown, Gareth; Brown, Jonathan; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruneliere, Renaud; Brunet, Sylvie; Bruni, Alessia; Bruni, Graziano; Bruschi, Marco; Bryngemark, Lene; Buanes, Trygve; Buat, Quentin; Bucci, Francesca; Buchholz, Peter; Buckingham, Ryan; Buckley, Andrew; Buda, Stelian Ioan; Budagov, Ioulian; Buehrer, Felix; Bugge, Lars; Bugge, Magnar Kopangen; Bulekov, Oleg; Bundock, Aaron Colin; Burckhart, Helfried; Burdin, Sergey; Burghgrave, Blake; Burke, Stephen; Burmeister, Ingo; Busato, Emmanuel; Büscher, Daniel; Büscher, Volker; Bussey, Peter; Buszello, Claus-Peter; Butler, Bart; Butler, John; Butt, Aatif Imtiaz; Buttar, Craig; Butterworth, Jonathan; Butti, Pierfrancesco; Buttinger, William; Buzatu, Adrian; Byszewski, Marcin; Cabrera Urbán, Susana; Caforio, Davide; Cakir, Orhan; Calafiura, Paolo; Calandri, Alessandro; Calderini, Giovanni; Calfayan, Philippe; Calkins, Robert; Caloba, Luiz; Calvet, David; Calvet, Samuel; Camacho Toro, Reina; Camarda, Stefano; Cameron, David; Caminada, Lea Michaela; Caminal Armadans, Roger; Campana, Simone; Campanelli, Mario; Campoverde, Angel; Canale, Vincenzo; Canepa, Anadi; Cantero, Josu; Cantrill, Robert; Cao, Tingting; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capua, Marcella; Caputo, Regina; Cardarelli, Roberto; Carli, Tancredi; Carlino, Gianpaolo; Carminati, Leonardo; Caron, Sascha; Carquin, Edson; Carrillo-Montoya, German D; Carter, Janet; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Casolino, Mirkoantonio; Castaneda-Miranda, Elizabeth; Castelli, Angelantonio; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catastini, Pierluigi; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Cattani, Giordano; Caughron, Seth; Cavaliere, Viviana; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Ceradini, Filippo; Cerio, Benjamin; Cerny, Karel; Cerqueira, Augusto Santiago; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cerv, Matevz; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chalupkova, Ina; Chan, Kevin; Chang, Philip; Chapleau, Bertrand; Chapman, John Derek; Charfeddine, Driss; Charlton, Dave; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Cheatham, Susan; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Karen; Chen, Liming; Chen, Shenjian; Chen, Xin; Chen, Yujiao; Cheng, Hok Chuen; Cheng, Yangyang; Cheplakov, Alexander; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Chevalier, Laurent; Chiarella, Vitaliano; Chiefari, Giovanni; Childers, John Taylor; Chilingarov, Alexandre; Chiodini, Gabriele; Chisholm, Andrew; Chislett, Rebecca Thalatta; Chitan, Adrian; Chizhov, Mihail; Chouridou, Sofia; Chow, Bonnie Kar Bo; Christidi, Ilektra-Athanasia; Chromek-Burckhart, Doris; Chu, Ming-Lee; Chudoba, Jiri; Chwastowski, Janusz; Chytka, Ladislav; Ciapetti, Guido; Ciftci, Abbas Kenan; Ciftci, Rena; Cinca, Diane; Cindro, Vladimir; Ciocio, Alessandra; Cirkovic, Predrag; Citron, Zvi Hirsh; Citterio, Mauro; Ciubancan, Mihai; Clark, Allan G; Clark, Philip James; Clarke, Robert; Cleland, Bill; Clemens, Jean-Claude; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Coffey, Laurel; Cogan, Joshua Godfrey; Coggeshall, James; Cole, Brian; Cole, Stephen; Colijn, Auke-Pieter; Collins-Tooth, Christopher; Collot, Johann; Colombo, Tommaso; Colon, German; Compostella, Gabriele; Conde Muiño, Patricia; Coniavitis, Elias; Conidi, Maria Chiara; Connell, Simon Henry; Connelly, Ian; Consonni, Sofia Maria; Consorti, Valerio; Constantinescu, Serban; Conta, Claudio; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Cooper-Smith, Neil; Copic, Katherine; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Corso-Radu, Alina; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Côté, David; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Crispin Ortuzar, Mireia; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cuciuc, Constantin-Mihai; Cuhadar Donszelmann, Tulay; Cummings, Jane; Curatolo, Maria; Cuthbert, Cameron; Czirr, Hendrik; Czodrowski, Patrick; Czyczula, Zofia; D'Auria, Saverio; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Daniells, Andrew Christopher; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darlea, Georgiana Lavinia; Darmora, Smita; Dassoulas, James; Dattagupta, Aparajita; Davey, Will; David, Claire; Davidek, Tomas; Davies, Eleanor; Davies, Merlin; Davignon, Olivier; Davison, Adam; Davison, Peter; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Castro, Stefano; De Cecco, Sandro; de Graat, Julien; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Nooij, Lucie; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; De Zorzi, Guido; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dechenaux, Benjamin; Dedovich, Dmitri; Degenhardt, James; Deigaard, Ingrid; Del Peso, Jose; Del Prete, Tarcisio; Deliot, Frederic; Delitzsch, Chris Malena; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; Deluca, Carolina; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Domenico, Antonio; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Dietzsch, Thorsten; Diglio, Sara; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dionisi, Carlo; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; do Vale, Maria Aline Barros; Do Valle Wemans, André; Doan, Thi Kieu Oanh; Dobos, Daniel; Dobson, Ellie; Doglioni, Caterina; Doherty, Tom; Dohmae, Takeshi; Dolejsi, Jiri; Dolezal, Zdenek; Dolgoshein, Boris; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Dris, Manolis; Dubbert, Jörg; Dube, Sourabh; Dubreuil, Emmanuelle; Duchovni, Ehud; Duckeck, Guenter; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Dudziak, Fanny; Duflot, Laurent; Duguid, Liam; Dührssen, Michael; Dunford, Monica; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Dwuznik, Michal; Dyndal, Mateusz; Ebke, Johannes; Edson, William; Edwards, Nicholas Charles; Ehrenfeld, Wolfgang; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Endner, Oliver Chris; Endo, Masaki; Engelmann, Roderich; Erdmann, Johannes; Ereditato, Antonio; Eriksson, Daniel; Ernis, Gunar; Ernst, Jesse; Ernst, Michael; Ernwein, Jean; Errede, Deborah; Errede, Steven; Ertel, Eugen; Escalier, Marc; Esch, Hendrik; Escobar, Carlos; Esposito, Bellisario; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Fabbri, Laura; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Favareto, Andrea; Fayard, Louis; Federic, Pavol; Fedin, Oleg; Fedorko, Wojciech; Fehling-Kaschek, Mirjam; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Haolu; Fenyuk, Alexander; Fernandez Perez, Sonia; Ferrag, Samir; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Julia; Fisher, Wade Cameron; Fitzgerald, Eric Andrew; Flechl, Martin; Fleck, Ivor; Fleischmann, Philipp; Fleischmann, Sebastian; Fletcher, Gareth Thomas; Fletcher, Gregory; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Florez Bustos, Andres Carlos; Flowerdew, Michael; Formica, Andrea; Forti, Alessandra; Fortin, Dominique; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Franchino, Silvia; Francis, David; Franklin, Melissa; Franz, Sebastien; Fraternali, Marco; French, Sky; Friedrich, Conrad; Friedrich, Felix; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fulsom, Bryan Gregory; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallo, Valentina Santina; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Gandrajula, Reddy Pratap; Gao, Jun; Gao, Yongsheng; Garay Walls, Francisca; Garberson, Ford; García, Carmen; García Navarro, José Enrique; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gatti, Claudio; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gauzzi, Paolo; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Ge, Peng; Gecse, Zoltan; Gee, Norman; Geerts, Daniël Alphonsus Adrianus; Geich-Gimbel, Christoph; Gellerstedt, Karl; Gemme, Claudia; Gemmell, Alistair; Genest, Marie-Hélène; Gentile, Simonetta; George, Matthias; George, Simon; Gerbaudo, Davide; Gershon, Avi; Ghazlane, Hamid; Ghodbane, Nabil; Giacobbe, Benedetto; Giagu, Stefano; Giangiobbe, Vincent; Giannetti, Paola; Gianotti, Fabiola; Gibbard, Bruce; Gibson, Stephen; Gilchriese, Murdock; Gillam, Thomas; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giokaris, Nikos; Giordani, MarioPaolo; Giordano, Raffaele; Giorgi, Francesco Michelangelo; Giraud, Pierre-Francois; Giugni, Danilo; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, Børge Kile; Gkialas, Ioannis; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Glonti, George; Goblirsch-Kolb, Maximilian; Goddard, Jack Robert; Godfrey, Jennifer; Godlewski, Jan; Goeringer, Christian; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gomez Fajardo, Luz Stella; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez Silva, Laura; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Gouighri, Mohamed; Goujdami, Driss; Goulette, Marc Phillippe; Goussiou, Anna; Goy, Corinne; Gozpinar, Serdar; Grabas, Herve Marie Xavier; Graber, Lars; Grabowska-Bold, Iwona; Grafström, Per; Grahn, Karl-Johan; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Grassi, Valerio; Gratchev, Vadim; Gray, Heather; Graziani, Enrico; Grebenyuk, Oleg; Greenwood, Zeno Dixon; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grishkevich, Yaroslav; Grivaz, Jean-Francois; Grohs, Johannes Philipp; Grohsjean, Alexander; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Groth-Jensen, Jacob; Grout, Zara Jane; Grybel, Kai; Guan, Liang; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Guicheney, Christophe; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Gunther, Jaroslav; Guo, Jun; Gupta, Shaun; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guttman, Nir; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Haefner, Petra; Hageboeck, Stephan; Hajduk, Zbigniew; Hakobyan, Hrachya; Haleem, Mahsana; Hall, David; Halladjian, Garabed; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamer, Matthias; Hamilton, Andrew; Hamilton, Samuel; Hamnett, Phillip George; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Hanke, Paul; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Harkusha, Siarhei; Harper, Devin; Harrington, Robert; Harris, Orin; Harrison, Paul Fraser; Hartjes, Fred; Hasegawa, Satoshi; Hasegawa, Yoji; Hasib, A; Hassani, Samira; Haug, Sigve; Hauschild, Michael; Hauser, Reiner; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hayashi, Takayasu; Hayden, Daniel; Hays, Chris; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Lukas; Heisterkamp, Simon; Hejbal, Jiri; Helary, Louis; Heller, Claudio; Heller, Matthieu; Hellman, Sten; Hellmich, Dennis; Helsens, Clement; Henderson, James; Henderson, Robert; Hengler, Christopher; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Hensel, Carsten; Herbert, Geoffrey Henry; Hernández Jiménez, Yesenia; Herrberg-Schubert, Ruth; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Hickling, Robert; Higón-Rodriguez, Emilio; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillert, Sonja; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hirose, Minoru; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoffman, Julia; Hoffmann, Dirk; Hofmann, Julia Isabell; Hohlfeld, Marc; Holmes, Tova Ray; Hong, Tae Min; Hooft van Huysduynen, Loek; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howard, Jacob; Howarth, James; Hrabovsky, Miroslav; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Diedi; Hu, Xueye; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hülsing, Tobias Alexander; Hurwitz, Martina; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Ideal, Emma; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikematsu, Katsumasa; Ikeno, Masahiro; Iliadis, Dimitrios; Ilic, Nikolina; Inamaru, Yuki; Ince, Tayfun; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Iturbe Ponce, Julia Mariana; Ivarsson, Jenny; Ivashin, Anton; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jackson, Brett; Jackson, Matthew; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jakubek, Jan; Jamin, David Olivier; Jana, Dilip; Jansen, Eric; Jansen, Hendrik; Janssen, Jens; Janus, Michel; Jarlskog, Göran; Javadov, Namig; Javůrek, Tomáš; Jeanty, Laura; Jeng, Geng-yuan; Jennens, David; Jenni, Peter; Jentzsch, Jennifer; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Ji, Weina; Jia, Jiangyong; Jiang, Yi; Jimenez Belenguer, Marcos; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Joergensen, Morten Dam; Johansson, Erik; Johansson, Per; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Ju, Xiangyang; Jung, Christian; Jungst, Ralph Markus; Jussel, Patrick; Juste Rozas, Aurelio; Kaci, Mohammed; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kajomovitz, Enrique; Kama, Sami; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kanno, Takayuki; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kar, Deepak; Karakostas, Konstantinos; Karastathis, Nikolaos; Karnevskiy, Mikhail; Karpov, Sergey; Karthik, Krishnaiyengar; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kasieczka, Gregor; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Katre, Akshay; Katzy, Judith; Kaushik, Venkatesh; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kazama, Shingo; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Kehoe, Robert; Keil, Markus; Keller, John; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Kessoku, Kohei; Keung, Justin; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Khodinov, Alexander; Khomich, Andrei; Khoo, Teng Jian; Khoriauli, Gia; Khoroshilov, Andrey; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hee Yeun; Kim, Hyeon Jin; Kim, Shinhong; Kimura, Naoki; Kind, Oliver; King, Barry; King, Matthew; King, Robert Steven Beaufoy; King, Samuel Burton; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kiss, Florian; Kitamura, Takumi; Kittelmann, Thomas; Kiuchi, Kenji; Kladiva, Eduard; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klioutchnikova, Tatiana; Klok, Peter; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koevesarki, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolanoski, Hermann; Koletsou, Iro; Koll, James; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; König, Sebastian; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Köpke, Lutz; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Korotkov, Vladislav; Kortner, Oliver; Kortner, Sandra; Kostyukhin, Vadim; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kral, Vlastimil; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitriy; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, Jana; Kravchenko, Anton; Kreiss, Sven; Kretz, Moritz; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Kruker, Tobias; Krumnack, Nils; Krumshteyn, Zinovii; Kruse, Amanda; Kruse, Mark; Kruskal, Michael; Kubota, Takashi; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuhl, Andrew; Kuhl, Thorsten; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kuna, Marine; Kunkle, Joshua; Kupco, Alexander; Kurashige, Hisaya; Kurochkin, Yurii; Kurumida, Rie; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; La Rosa, Alessandro; La Rotonda, Laura; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Laier, Heiko; Lambourne, Luke; Lammers, Sabine; Lampen, Caleb; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lang, Valerie Susanne; Lange, Clemens; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Lassnig, Mario; Laurelli, Paolo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Le, Bao Tran; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Menedeu, Eve; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Claire, Alexandra; Lee, Hurng-Chun; Lee, Jason; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Guillaume; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehan, Allan; Lehmacher, Marc; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leister, Andrew Gerard; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzen, Georg; Lenzi, Bruno; Leone, Robert; Leonhardt, Kathrin; Leontsinis, Stefanos; Leroy, Claude; Lester, Christopher; Lester, Christopher Michael; Levchenko, Mikhail; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levy, Mark; Lewis, Adrian; Lewis, George; Leyko, Agnieszka; Leyton, Michael; Li, Bing; Li, Bo; Li, Haifeng; Li, Ho Ling; Li, Liang; Li, Shu; Li, Yichen; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Lichard, Peter; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Limper, Maaike; Lin, Simon; Linde, Frank; Lindquist, Brian Edward; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Bo; Liu, Dong; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Miaoyuan; Liu, Minghui; Liu, Yanwen; Livan, Michele; Livermore, Sarah; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo Sterzo, Francesco; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loddenkoetter, Thomas; Loebinger, Fred; Loevschall-Jensen, Ask Emil; Loginov, Andrey; Loh, Chang Wei; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Lombardo, Vincenzo Paolo; Long, Brian Alexander; Long, Jonathan; Long, Robin Eamonn; Lopes, Lourenco; Lopez Mateos, David; Lopez Paredes, Brais; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Lou, XinChou; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lowe, Andrew; Lu, Feng; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lundberg, Olof; Lund-Jensen, Bengt; Lungwitz, Matthias; Lynn, David; Lysak, Roman; Lytken, Else; Ma, Hong; Ma, Lian Liang; Maccarrone, Giovanni; Macchiolo, Anna; Machado Miguens, Joana; Macina, Daniela; Madaffari, Daniele; Madar, Romain; Maddocks, Harvey Jonathan; Mader, Wolfgang; Madsen, Alexander; Maeno, Mayuko; Maeno, Tadashi; Magradze, Erekle; Mahboubi, Kambiz; Mahlstedt, Joern; Mahmoud, Sara; Maiani, Camilla; Maidantchik, Carmen; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Mal, Prolay; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mamuzic, Judita; Mandelli, Beatrice; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Manfredini, Alessandro; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany Andreina; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mantifel, Rodger; Mapelli, Livio; March, Luis; Marchand, Jean-Francois; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marques, Carlos; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Marti, Lukas Fritz; Marti-Garcia, Salvador; Martin, Brian; Martin, Brian; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Homero; Martinez, Mario; Martin-Haugh, Stewart; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massol, Nicolas; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Matsunaga, Hiroyuki; Matsushita, Takashi; Mättig, Peter; Mättig, Stefan; Mattmann, Johannes; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Mazzaferro, Luca; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; Mchedlidze, Gvantsa; Mclaughlan, Tom; McMahon, Steve; McPherson, Robert; Meade, Andrew; Mechnich, Joerg; Medinnis, Michael; Meehan, Samuel; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meineck, Christian; Meirose, Bernhard; Melachrinos, Constantinos; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Mergelmeyer, Sebastian; Meric, Nicolas; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Merritt, Hayes; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Middleton, Robin; Migas, Sylwia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Milstein, Dmitry; Minaenko, Andrey; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mirabelli, Giovanni; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Mitsui, Shingo; Miucci, Antonio; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Mochizuki, Kazuya; Moeller, Victoria; Mohapatra, Soumya; Mohr, Wolfgang; Molander, Simon; Moles-Valls, Regina; Mönig, Klaus; Monini, Caterina; Monk, James; Monnier, Emmanuel; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Moraes, Arthur; Morange, Nicolas; Morel, Julien; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morii, Masahiro; Moritz, Sebastian; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Morvaj, Ljiljana; Moser, Hans-Guenther; Mosidze, Maia; Moss, Josh; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Muanza, Steve; Mudd, Richard; Mueller, Felix; Mueller, James; Mueller, Klemens; Mueller, Thibaut; Mueller, Timo; Muenstermann, Daniel; Munwes, Yonathan; Murillo Quijada, Javier Alberto; Murray, Bill; Musheghyan, Haykuhi; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nackenhorst, Olaf; Nadal, Jordi; Nagai, Koichi; Nagai, Ryo; Nagai, Yoshikazu; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagel, Martin; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Namasivayam, Harisankar; Nanava, Gizo; Narayan, Rohin; Nattermann, Till; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Negri, Andrea; Negri, Guido; Negrini, Matteo; Nektarijevic, Snezana; Nelson, Andrew; Nelson, Timothy Knight; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen, Duong Hai; Nickerson, Richard; Nicolaidou, Rosy; Nicquevert, Bertrand; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolics, Katalin; Nikolopoulos, Konstantinos; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nodulman, Lawrence; Nomachi, Masaharu; Nomidis, Ioannis; Norberg, Scarlet; Nordberg, Markus; Nowak, Sebastian; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; Nuti, Francesco; O'Brien, Brendan Joseph; O'grady, Fionnbarr; O'Neil, Dugan; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Oda, Susumu; Odaka, Shigeru; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Ohshima, Takayoshi; Okamura, Wataru; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olchevski, Alexander; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ouellette, Eric; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Padilla Aranda, Cristobal; Pagáčová, Martina; Pagan Griso, Simone; Paganis, Efstathios; Pahl, Christoph; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Palestini, Sandro; Pallin, Dominique; Palma, Alberto; Palmer, Jody; Pan, Yibin; Panagiotopoulou, Evgenia; Panduro Vazquez, William; Pani, Priscilla; Panikashvili, Natalia; Panitkin, Sergey; Pantea, Dan; Paolozzi, Lorenzo; Papadopoulou, Theodora; Papageorgiou, Konstantinos; Paramonov, Alexander; Paredes Hernandez, Daniela; Parker, Michael Andrew; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pasqualucci, Enrico; Passaggio, Stefano; Passeri, Antonio; Pastore, Fernanda; Pastore, Francesca; Pásztor, Gabriella; Pataraia, Sophio; Patel, Nikhul; Pater, Joleen; Patricelli, Sergio; Pauly, Thilo; Pearce, James; Pedersen, Maiken; Pedraza Lopez, Sebastian; Pedro, Rute; Peleganchuk, Sergey; Pelikan, Daniel; Peng, Haiping; Penning, Bjoern; Penwell, John; Perepelitsa, Dennis; Perez Codina, Estel; Pérez García-Estañ, María Teresa; Perez Reale, Valeria; Perini, Laura; Pernegger, Heinz; Perrino, Roberto; Peschke, Richard; Peshekhonov, Vladimir; Peters, Krisztian; Peters, Yvonne; Petersen, Brian; Petersen, Jorgen; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petrolo, Emilio; Petrucci, Fabrizio; Petteni, Michele; Pettersson, Nora Emilia; Pezoa, Raquel; Phillips, Peter William; Piacquadio, Giacinto; Pianori, Elisabetta; Picazio, Attilio; Piccaro, Elisa; Piccinini, Maurizio; Piegaia, Ricardo; Pignotti, David; Pilcher, James; Pilkington, Andrew; Pina, João Antonio; Pinamonti, Michele; Pinder, Alex; Pinfold, James; Pingel, Almut; Pinto, Belmiro; Pires, Sylvestre; Pitt, Michael; Pizio, Caterina; Pleier, Marc-Andre; Pleskot, Vojtech; Plotnikova, Elena; Plucinski, Pawel; Poddar, Sahill; Podlyski, Fabrice; Poettgen, Ruth; Poggioli, Luc; Pohl, David-leon; Pohl, Martin; Polesello, Giacomo; Policicchio, Antonio; Polifka, Richard; Polini, Alessandro; Pollard, Christopher Samuel; Polychronakos, Venetios; Pommès, Kathy; Pontecorvo, Ludovico; Pope, Bernard; Popeneciu, Gabriel Alexandru; Popovic, Dragan; Poppleton, Alan; Portell Bueso, Xavier; Pospelov, Guennady; Pospisil, Stanislav; Potamianos, Karolos; Potrap, Igor; Potter, Christina; Potter, Christopher; Poulard, Gilbert; Poveda, Joaquin; Pozdnyakov, Valery; Pralavorio, Pascal; Pranko, Aliaksandr; Prasad, Srivas; Pravahan, Rishiraj; Prell, Soeren; Price, Darren; Price, Joe; Price, Lawrence; Prieur, Damien; Primavera, Margherita; Proissl, Manuel; Prokofiev, Kirill; Prokoshin, Fedor; Protopapadaki, Eftychia-sofia; Protopopescu, Serban; Proudfoot, James; Przybycien, Mariusz; Przysiezniak, Helenka; Ptacek, Elizabeth; Pueschel, Elisa; Puldon, David; Purohit, Milind; Puzo, Patrick; Qian, Jianming; Qin, Gang; Qin, Yang; Quadt, Arnulf; Quarrie, David; Quayle, William; Quilty, Donnchadha; Qureshi, Anum; Radeka, Veljko; Radescu, Voica; Radhakrishnan, Sooraj Krishnan; Radloff, Peter; Rados, Pere; Ragusa, Francesco; Rahal, Ghita; Rajagopalan, Srinivasan; Rammensee, Michael; Randle-Conde, Aidan Sean; Rangel-Smith, Camila; Rao, Kanury; Rauscher, Felix; Rave, Tobias Christian; Ravenscroft, Thomas; Raymond, Michel; Read, Alexander Lincoln; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reeves, Kendall; Rehnisch, Laura; Reinsch, Andreas; Reisin, Hernan; Relich, Matthew; Rembser, Christoph; Ren, Zhongliang; Renaud, Adrien; Rescigno, Marco; Resconi, Silvia; Rezanova, Olga; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Ridel, Melissa; Rieck, Patrick; Rijssenbeek, Michael; Rimoldi, Adele; Rinaldi, Lorenzo; Ritsch, Elmar; Riu, Imma; Rizatdinova, Flera; Rizvi, Eram; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Roda, Chiara; Rodrigues, Luis; Roe, Shaun; Røhne, Ole; Rolli, Simona; Romaniouk, Anatoli; Romano, Marino; Romeo, Gaston; Romero Adam, Elena; Rompotis, Nikolaos; Roos, Lydia; Ros, Eduardo; Rosati, Stefano; Rosbach, Kilian; Rose, Matthew; Rosendahl, Peter Lundgaard; Rosenthal, Oliver; Rossetti, Valerio; Rossi, Elvira; Rossi, Leonardo Paolo; Rosten, Rachel; Rotaru, Marina; Roth, Itamar; Rothberg, Joseph; Rousseau, David; Royon, Christophe; Rozanov, Alexandre; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rubinskiy, Igor; Rud, Viacheslav; Rudolph, Christian; Rudolph, Matthew Scott; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rurikova, Zuzana; Rusakovich, Nikolai; Ruschke, Alexander; Rutherfoord, John; Ruthmann, Nils; Ryabov, Yury; Rybar, Martin; Rybkin, Grigori; Ryder, Nick; Saavedra, Aldo; Sacerdoti, Sabrina; Saddique, Asif; Sadeh, Iftach; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Sakamoto, Hiroshi; Sakurai, Yuki; Salamanna, Giuseppe; Salamon, Andrea; Saleem, Muhammad; Salek, David; Sales De Bruin, Pedro Henrique; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvachua Ferrando, Belén; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sampsonidis, Dimitrios; Sanchez, Arturo; Sánchez, Javier; Sanchez Martinez, Victoria; Sandaker, Heidi; Sandbach, Ruth Laura; Sander, Heinz Georg; Sanders, Michiel; Sandhoff, Marisa; Sandoval, Tanya; Sandoval, Carlos; Sandstroem, Rikard; Sankey, Dave; Sansoni, Andrea; Santoni, Claudio; Santonico, Rinaldo; Santos, Helena; Santoyo Castillo, Itzebelt; Sapp, Kevin; Sapronov, Andrey; Saraiva, João; Sarrazin, Bjorn; Sartisohn, Georg; Sasaki, Osamu; Sasaki, Yuichi; Sauvage, Gilles; Sauvan, Emmanuel; Savard, Pierre; Savu, Dan Octavian; Sawyer, Craig; Sawyer, Lee; Saxon, David; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scanlon, Tim; Scannicchio, Diana; Scarcella, Mark; Schaarschmidt, Jana; Schacht, Peter; Schaefer, Douglas; Schaefer, Ralph; Schaepe, Steffen; Schaetzel, Sebastian; Schäfer, Uli; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R~Dean; Scharf, Veit; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Scherzer, Max; Schiavi, Carlo; Schieck, Jochen; Schillo, Christian; Schioppa, Marco; Schlenker, Stefan; Schmidt, Evelyn; Schmieden, Kristof; Schmitt, Christian; Schmitt, Christopher; Schmitt, Sebastian; Schneider, Basil; Schnellbach, Yan Jie; Schnoor, Ulrike; Schoeffel, Laurent; Schoening, Andre; Schoenrock, Bradley Daniel; Schorlemmer, Andre Lukas; Schott, Matthias; Schouten, Doug; Schovancova, Jaroslava; Schramm, Steven; Schreyer, Manuel; Schroeder, Christian; Schuh, Natascha; Schultens, Martin Johannes; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwartzman, Ariel; Schwegler, Philipp; Schwemling, Philippe; Schwienhorst, Reinhard; Schwindling, Jerome; Schwindt, Thomas; Schwoerer, Maud; Sciacca, Gianfranco; Scifo, Estelle; Sciolla, Gabriella; Scott, Bill; Scuri, Fabrizio; Scutti, Federico; Searcy, Jacob; Sedov, George; Sedykh, Evgeny; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekula, Stephen; Selbach, Karoline Elfriede; Seliverstov, Dmitry; Sellers, Graham; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Serre, Thomas; Seuster, Rolf; Severini, Horst; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shamim, Mansoora; Shan, Lianyou; Shank, James; Shao, Qi Tao; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Sherwood, Peter; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shiyakova, Mariya; Shmeleva, Alevtina; Shochet, Mel; Short, Daniel; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Shushkevich, Stanislav; Sicho, Petr; Sidorov, Dmitri; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silbert, Ohad; Silva, José; Silver, Yiftah; Silverstein, Daniel; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simoniello, Rosa; Simonyan, Margar; Sinervo, Pekka; Sinev, Nikolai; Sipica, Valentin; Siragusa, Giovanni; Sircar, Anirvan; Sisakyan, Alexei; Sivoklokov, Serguei; Sjölin, Jörgen; Sjursen, Therese; Skottowe, Hugh Philip; Skovpen, Kirill; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Sliwa, Krzysztof; Smakhtin, Vladimir; Smart, Ben; Smestad, Lillian; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Kenway; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snidero, Giacomo; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffer, Abner; Soh, Dart-yin; Solans, Carlos; Solar, Michael; Solc, Jaroslav; Soldatov, Evgeny; Soldevila, Urmila; Solfaroli Camillocci, Elena; Solodkov, Alexander; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Song, Hong Ye; Soni, Nitesh; Sood, Alexander; Sopczak, Andre; Sopko, Vit; Sopko, Bruno; Sorin, Veronica; Sosebee, Mark; Soualah, Rachik; Soueid, Paul; Soukharev, Andrey; South, David; Spagnolo, Stefania; Spanò, Francesco; Spearman, William Robert; Spighi, Roberto; Spigo, Giancarlo; Spousta, Martin; Spreitzer, Teresa; Spurlock, Barry; St Denis, Richard Dante; Staerz, Steffen; Stahlman, Jonathan; Stamen, Rainer; Stanecka, Ewa; Stanek, Robert; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stanitzki, Marcel Michael; Stapnes, Steinar; Starchenko, Evgeny; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Staszewski, Rafal; Stavina, Pavel; Steele, Genevieve; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stern, Sebastian; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoebe, Michael; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Stradling, Alden; Straessner, Arno; Stramaglia, Maria Elena; Strandberg, Jonas; Strandberg, Sara; Strandlie, Are; Strauss, Emanuel; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Stroynowski, Ryszard; Stucci, Stefania Antonia; Stugu, Bjarne; Styles, Nicholas Adam; Su, Dong; Su, Jun; Subramania, Halasya Siva; Subramaniam, Rajivalochan; Succurro, Antonella; Sugaya, Yorihito; Suhr, Chad; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Susinno, Giancarlo; Sutton, Mark; Suzuki, Yu; Svatos, Michal; Swedish, Stephen; Swiatlowski, Maximilian; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takahashi, Yuta; Takai, Helio; Takashima, Ryuichi; Takeda, Hiroshi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tam, Jason; Tamsett, Matthew; Tan, Kong Guan; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Satoshi; Tanaka, Shuji; Tanasijczuk, Andres Jorge; Tani, Kazutoshi; Tannoury, Nancy; Tapprogge, Stefan; Tarem, Shlomit; Tarrade, Fabien; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Frank; Taylor, Geoffrey; Taylor, Wendy; Teischinger, Florian Alfred; Teixeira Dias Castanheira, Matilde; Teixeira-Dias, Pedro; Temming, Kim Katrin; Ten Kate, Herman; Teng, Ping-Kun; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Therhaag, Jan; Theveneaux-Pelzer, Timothée; Thoma, Sascha; Thomas, Juergen; Thomas-Wilsker, Joshuha; Thompson, Emily; Thompson, Paul; Thompson, Peter; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Thong, Wai Meng; Thun, Rudolf; Tian, Feng; Tibbetts, Mark James; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tiouchichine, Elodie; Tipton, Paul; Tisserant, Sylvain; Todorov, Theodore; Todorova-Nova, Sharka; Toggerson, Brokk; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tollefson, Kirsten; Tomlinson, Lee; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Topilin, Nikolai; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Tran, Huong Lan; Trefzger, Thomas; Tremblet, Louis; Tricoli, Alessandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Triplett, Nathan; Trischuk, William; Trocmé, Benjamin; Troncon, Clara; Trottier-McDonald, Michel; Trovatelli, Monica; True, Patrick; Trzebinski, Maciej; Trzupek, Adam; Tsarouchas, Charilaos; Tseng, Jeffrey; Tsiareshka, Pavel; Tsionou, Dimitra; Tsipolitis, Georgios; Tsirintanis, Nikolaos; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsuno, Soshi; Tsybychev, Dmitri; Tudorache, Alexandra; Tudorache, Valentina; Tuna, Alexander Naip; Tupputi, Salvatore; Turchikhin, Semen; Turecek, Daniel; Turk Cakir, Ilkay; Turra, Ruggero; Tuts, Michael; Tykhonov, Andrii; Tylmad, Maja; Tyndel, Mike; Uchida, Kirika; Ueda, Ikuo; Ueno, Ryuichi; Ughetto, Michael; Ugland, Maren; Uhlenbrock, Mathias; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Ungaro, Francesca; Unno, Yoshinobu; Urbaniec, Dustin; Urquijo, Phillip; Usai, Giulio; Usanova, Anna; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Valencic, Nika; Valentinetti, Sara; Valero, Alberto; Valery, Loic; Valkar, Stefan; Valladolid Gallego, Eva; Vallecorsa, Sofia; Valls Ferrer, Juan Antonio; Van Der Deijl, Pieter; van der Geer, Rogier; van der Graaf, Harry; Van Der Leeuw, Robin; van der Ster, Daniel; van Eldik, Niels; van Gemmeren, Peter; Van Nieuwkoop, Jacobus; van Vulpen, Ivo; van Woerden, Marius Cornelis; Vanadia, Marco; Vandelli, Wainer; Vanguri, Rami; Vaniachine, Alexandre; Vankov, Peter; Vannucci, Francois; Vardanyan, Gagik; Vari, Riccardo; Varnes, Erich; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vazeille, Francois; Vazquez Schroeder, Tamara; Veatch, Jason; Veloso, Filipe; Veneziano, Stefano; Ventura, Andrea; Ventura, Daniel; Venturi, Manuela; Venturi, Nicola; Venturini, Alessio; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Jos; Vest, Anja; Vetterli, Michel; Viazlo, Oleksandr; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Vigne, Ralph; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinogradov, Vladimir; Virzi, Joseph; Vivarelli, Iacopo; Vives Vaque, Francesc; Vlachos, Sotirios; Vladoiu, Dan; Vlasak, Michal; Vogel, Adrian; Vokac, Petr; Volpi, Guido; Volpi, Matteo; von der Schmitt, Hans; von Radziewski, Holger; von Toerne, Eckhard; Vorobel, Vit; Vorobev, Konstantin; Vos, Marcel; Voss, Rudiger; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vu Anh, Tuan; Vuillermet, Raphael; Vukotic, Ilija; Vykydal, Zdenek; Wagner, Wolfgang; Wagner, Peter; Wahrmund, Sebastian; Wakabayashi, Jun; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wall, Richard; Waller, Peter; Walsh, Brian; Wang, Chao; Wang, Chiho; Wang, Fuquan; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Kuhan; Wang, Rui; Wang, Song-Ming; Wang, Tan; Wang, Xiaoxiao; Wanotayaroj, Chaowaroj; Warburton, Andreas; Ward, Patricia; Wardrope, David Robert; Warsinsky, Markus; Washbrook, Andrew; Wasicki, Christoph; Watanabe, Ippei; Watkins, Peter; Watson, Alan; Watson, Ian; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Ben; Webb, Samuel; Weber, Michele; Weber, Stefan Wolf; Webster, Jordan S; Weidberg, Anthony; Weigell, Philipp; Weinert, Benjamin; Weingarten, Jens; Weiser, Christian; Weits, Hartger; Wells, Phillippa; Wenaus, Torre; Wendland, Dennis; Weng, Zhili; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Matthias; Werner, Per; Wessels, Martin; Wetter, Jeffrey; Whalen, Kathleen; White, Andrew; White, Martin; White, Ryan; White, Sebastian; Whiteson, Daniel; Wicke, Daniel; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wienemann, Peter; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wijeratne, Peter Alexander; Wildauer, Andreas; Wildt, Martin Andre; Wilkens, Henric George; Will, Jonas Zacharias; Williams, Hugh; Williams, Sarah; Willis, Christopher; Willocq, Stephane; Wilson, John; Wilson, Alan; Wingerter-Seez, Isabelle; Winklmeier, Frank; Wittgen, Matthias; Wittig, Tobias; Wittkowski, Josephine; Wollstadt, Simon Jakob; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wosiek, Barbara; Wotschack, Jorg; Woudstra, Martin; Wozniak, Krzysztof; Wright, Michael; Wu, Mengqing; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wulf, Evan; Wyatt, Terry Richard; Wynne, Benjamin; Xella, Stefania; Xiao, Meng; Xu, Da; Xu, Lailin; Yabsley, Bruce; Yacoob, Sahal; Yamada, Miho; Yamaguchi, Hiroshi; Yamaguchi, Yohei; Yamamoto, Akira; Yamamoto, Kyoko; Yamamoto, Shimpei; Yamamura, Taiki; Yamanaka, Takashi; Yamauchi, Katsuya; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Hongtao; Yang, Un-Ki; Yang, Yi; Yanush, Serguei; Yao, Liwen; Yao, Weiming; Yasu, Yoshiji; Yatsenko, Elena; Yau Wong, Kaven Henry; Ye, Jingbo; Ye, Shuwei; Yen, Andy L; Yildirim, Eda; Yilmaz, Metin; Yoosoofmiya, Reza; Yorita, Kohei; Yoshida, Rikutaro; Yoshihara, Keisuke; Young, Charles; Young, Christopher John; Youssef, Saul; Yu, David Ren-Hwa; Yu, Jaehoon; Yu, Jiaming; Yu, Jie; Yuan, Li; Yurkewicz, Adam; Zabinski, Bartlomiej; Zaidan, Remi; Zaitsev, Alexander; Zaman, Aungshuman; Zambito, Stefano; Zanello, Lucia; Zanzi, Daniele; Zaytsev, Alexander; Zeitnitz, Christian; Zeman, Martin; Zemla, Andrzej; Zengel, Keith; Zenin, Oleg; Ženiš, Tibor; Zerwas, Dirk; Zevi della Porta, Giovanni; Zhang, Dongliang; Zhang, Fangzhou; Zhang, Huaqiao; Zhang, Jinlong; Zhang, Lei; Zhang, Xueyao; Zhang, Zhiqing; Zhao, Zhengguo; Zhemchugov, Alexey; Zhong, Jiahang; Zhou, Bing; Zhou, Lei; Zhou, Ning; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zibell, Andre; Zieminska, Daria; Zimine, Nikolai; Zimmermann, Christoph; Zimmermann, Robert; Zimmermann, Simone; Zimmermann, Stephanie; Zinonos, Zinonas; Ziolkowski, Michael; Zobernig, Georg; Zoccoli, Antonio; zur Nedden, Martin; Zurzolo, Giovanni; Zutshi, Vishnu; Zwalinski, Lukasz

    2014-01-01

    The integrated elliptic flow of charged particles produced in Pb+Pb collisions at $\\sqrt{s_{NN}}=2.76$ TeV has been measured with the ATLAS detector using data collected at the Large Hadron Collider. The anisotropy parameter, $v_2$, was measured in the pseudorapidity range $|\\eta|\\leq$ 2.5 with the event-plane method. In order to include tracks with very low transverse momentum $p_T$, thus reducing the uncertainty in $v_2$ integrated over $p_T$, a $1 \\mu b^{-1}$ data sample recorded without a magnetic field in the tracking detectors is used. The centrality dependence of the integrated $v_2$ is compared to other measurements obtained with higher $p_T$ thresholds. A weak pseudorapidity dependence of the integrated elliptic flow is observed for central collisions, and a small decrease when moving away from mid-rapidity is observed only in peripheral collisions. The integrated $v_2$ transformed to the rest frame of one of the colliding nuclei is compared to the lower-energy RHIC data.

  5. [The role of the basal forebrain cholinergic dysfunction in pathogenesis of declarative memory disorder in Alzheimer's disease].

    Science.gov (United States)

    Mukhin, V N

    2013-06-01

    Alzheimer's disease is the most common cause of the declarative memory disorder: 30-40% cases of dementia among all of age groups, and 50-60% among the people older 65 years. In addition, disorder of declarative memory is the genuine symptom of the disease, which certainly appears on early stage of the disease and it is an obligate diagnostic symptom. Proponents of the "cholinergic theory" of pathogenesis of Alzheimer's disease suggest that the basis disorder of declarative memory is cholinergic dysfunction. Several neurodynamic mechanisms associated with declarative memory depend on the level of acetylcholine in hippocampus and neocortex. It is believed that dysfunction of the basal cholinergic system in Alzheimer's disease leads to the impairment of these mechanisms. In this review, we summarize available literature data concerning the mechanisms of Alzheimer's disease. PMID:24459876

  6. In vivo PET imaging of brain nicotinic cholinergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Bottlaender, M.; Valette, H.; Saba, W.; Schollhorn-Peyronneau, M.A.; Dolle, F.; Syrota, A. [Service Hospitalier Frederic Joliot (CEA/DSV/DRM), 91 - Orsay (France)

    2006-07-01

    Neuronal acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system where they modulate a number of CNS functions including neurotransmitter release, cognitive function, anxiety, analgesia and control of cerebral blood flow. In the brain, a major subtype is composed of the {alpha}4{beta}2 subunit combination. Density of this subtype has been shown to be decreased in patients with neuro-degenerative disease such as Alzheimer and Parkinson's disease (AD and PD), and mutated receptors has been described in some familial epilepsy. Thus, in vivo mapping of the nicotinic nAChRs by Positron Emission Tomography (PET) are of great interest to monitor the evolution of these pathologies and changes in the neuronal biochemistry induced by therapeutic agents. Recently, a new compound, 3-[2(S)-2-azetidinyl-methoxy]pyridine (A-85380) has been synthesised and labelled with fluorine-18, [{sup 18}F]fluoro-A-85380 (Dolle et al., 1999). The [{sup 18}F]fluoro-A-85380 has been shown to bind with high affinity t o nAChRs in vitro (Saba et al., 2004), and its toxicity was low and compatible with it s use at tracer dose in human PET studies (Valette, 2002). PET studies in baboons showed that, after in vivo administration of [ {sup 18}F]fluoro-A-85380 at a tracer dose, the distribution of the radioactivity in the brain reflect the distribution of the < 4R2 nAChRs. Competition and pre-blocking studies, using nicotinic agonists, confirm that the radiotracer binds specifically to the heteromeric nAChRs in the brain (Valette et al., 1999). The in vivo, characteristics of the [{sup 18}F]fluoro-A-8538 0 combined with its low toxicity make possible the imaging of the nicotinic receptor s in human by PET (Bottlaender 2003). Studies were performed in healthy non-smoker volunteers to evaluate the brain kinetics of [{sup 18}F]fluoro-A-85380 and to assess the quantification of its nAChRs binding in the human brain with PET (Gallezot et a., 2005). The [{sup 18}F

  7. Failure of cholinergic stimulation to induce a secretory response from the rectal mucosa in cystic fibrosis.

    OpenAIRE

    Hardcastle, J; Hardcastle, P T; Taylor, C J; Goldhill, J

    1991-01-01

    The secretory response to cholinergic stimulation was investigated in rectal biopsy specimens from children with cystic fibrosis and a control group using a modified Ussing chamber technique. Acetylcholine (10(-3) mol/l) increased the short circuit current in 12 control specimens by mean (SEM) 83.0 (16.4) microA/cm2, but samples from five children with cystic fibrosis failed to exhibit such a response (-1.4 (3.2) microA/cm2). Amiloride (10(-4) mol/l), which will inhibit electrogenic sodium ab...

  8. Control of heart rate during thermoregulation in the heliothermic lizard Pogona barbata: importance of cholinergic and adrenergic mechanisms.

    Science.gov (United States)

    Seebacher, F; Franklin, C E

    2001-12-01

    During thermoregulation in the bearded dragon Pogona barbata, heart rate when heating is significantly faster than when cooling at any given body temperature (heart rate hysteresis), resulting in faster rates of heating than cooling. However, the mechanisms that control heart rate during heating and cooling are unknown. The aim of this study was to test the hypothesis that changes in cholinergic and adrenergic tone on the heart are responsible for the heart rate hysteresis during heating and cooling in P. barbata. Heating and cooling trials were conducted before and after the administration of atropine, a muscarinic antagonist, and sotalol, a beta-adrenergic antagonist. Cholinergic and beta-adrenergic blockade did not abolish the heart rate hysteresis, as the heart rate during heating was significantly faster than during cooling in all cases. Adrenergic tone was extremely high (92.3 %) at the commencement of heating, and decreased to 30.7 % at the end of the cooling period. Moreover, in four lizards there was an instantaneous drop in heart rate (up to 15 beats min(-1)) as the heat source was switched off, and this drop in heart rate coincided with either a drop in beta-adrenergic tone or an increase in cholinergic tone. Rates of heating were significantly faster during the cholinergic blockade, and least with a combined cholinergic and beta-adrenergic blockade. The results showed that cholinergic and beta-adrenergic systems are not the only control mechanisms acting on the heart during heating and cooling, but they do have a significant effect on heart rate and on rates of heating and cooling. PMID:11815660

  9. Estimating Groundwater Concentrations from Mass Releases to the Aquifer at Integrated Disposal Facility and Tank Farm Locations Within the Central Plateau of the Hanford Site

    Energy Technology Data Exchange (ETDEWEB)

    Bergeron, Marcel P.; Freeman, Eugene J.

    2005-06-09

    This report summarizes groundwater-related numerical calculations that will support groundwater flow and transport analyses associated with the scheduled 2005 performance assessment of the Integrated Disposal Facility (IDF) at the Hanford Site. The report also provides potential supporting information to other ongoing Hanford Site risk analyses associated with the closure of single-shell tank farms and related actions. The IDF 2005 performance assessment analysis is using well intercept factors (WIFs), as outlined in the 2001 performance assessment of the IDF. The flow and transport analyses applied to these calculations use both a site-wide regional-scale model and a local-scale model of the area near the IDF. The regional-scale model is used to evaluate flow conditions, groundwater transport, and impacts from the IDF in the central part of the Hanford Site, at the core zone boundary around the 200 East and 200 West Areas, and along the Columbia River. The local-scale model is used to evaluate impacts from transport of contaminants to a hypothetical well 100 m downgradient from the IDF boundaries. Analyses similar to the regional-scale analysis of IDF releases are also provided at individual tank farm areas as additional information. To gain insight on how the WIF approach compares with other approaches for estimating groundwater concentrations from mass releases to the unconfined aquifer, groundwater concentrations were estimated with the WIF approach for two hypothetical release scenarios and compared with similar results using a calculational approach (the convolution approach). One release scenario evaluated with both approaches (WIF and convolution) involved a long-term source release from immobilized low-activity waste glass containing 25,550 Ci of technetium-99 near the IDF; another involved a hypothetical shorter-term release of {approx}0.7 Ci of technetium over 600 years from the S-SX tank farm area. In addition, direct simulation results for both release

  10. Effects of massive wind power integration on short-term water resource management in central Chile - a grid-wide study

    Science.gov (United States)

    Haas, J.; Olivares, M. A.; Palma, R.

    2013-12-01

    In central Chile, water from reservoirs and streams is mainly used for irrigation and power generation. Hydropower reservoirs operation is particularly challenging because: i) decisions at each plant impact the entire power system, and ii) the existence of large storage capacity implies inter-temporal ties. An Independent System Operator (ISO) decides the grid-wide optimal allocation of water for power generation, under irrigation-related constraints. To account for the long-term opportunity cost of water, a future cost function is determined and used in the short term planning. As population growth and green policies demand increasing levels of renewable energy in power systems, deployment of wind farms and solar plants is rising quickly. However, their power output is highly fluctuating on short time scales, affecting the operation of power plants, particularly those fast responding units as hydropower reservoirs. This study addresses these indirect consequences of massive introduction of green energy sources on reservoir operations. Short-term reservoir operation, under different wind penetration scenarios, is simulated using a replica of Chile's ISO's scheduling optimization tools. Furthermore, an ongoing study is exploring the potential to augment the capacity the existing hydro-power plants to better cope with the balancing needs due to a higher wind power share in the system. As reservoir releases determine to a great extent flows at downstream locations, hourly time series of turbined flows for 24-hour periods were computed for selected combinations between new wind farms and increased capacity of existing hydropower plants. These time series are compiled into subdaily hydrologic alteration (SDHA) indexes (Zimmerman et al, 2010). The resulting sample of indexes is then analyzed using duration curves. Results show a clear increase in the SDHA for every reservoir of the system as more fluctuating renewables are integrated into the system. High

  11. Cholinergic cells in the nucleus basalis of mice express the N-methyl-D-aspartate-receptor subunit NR2C and its replacement by the NR2B subunit enhances frontal and amygdaloid acetylcholine levels

    NARCIS (Netherlands)

    De Souza Silva, M. A.; Dolga, Amalia; Pieri, I.; Marchetti, L.; Eisel, U. L. M.; Huston, J. P.; Dere, E.

    2006-01-01

    It is known that glutamatergic and cholinergic systems interact functionally at the level of the cholinergic basal forebrain. The N-methyl-D-aspartate receptor (NMDA-R) is a multiprotein complex composed of NR1, NR2 and/or NR3 subunits. The subunit composition of NMDA-R of cholinergic cells in the n

  12. The Protective Effect of Electroacupuncturing Zusanli Points on Hemorrhagic Shock Rats through Cholinergic Anti-inflammatory Pathway

    Institute of Scientific and Technical Information of China (English)

    Zhao-Hui DU; Jian-Guo LI; Yan-Lin WANG; Zhou-Quan PENG; Xiao-Feng YE

    2005-01-01

    @@ 1 Introduction In conditions of circulatory shock, systemic inflammatory response (SIRS) plays a funda mental pathogenetic role, with activation of transcription nuclear factors(mainly NF- kB) and markedly increased production of cytokines (mainly TNF-a), which trigger the inflammatory cascade active ation. Recent research have identified a basic neural pathway that reflexively monitors and adjusts such response. It is through the rapid activation (in "real-time") of efferent vagus nerve fibres(the recentlyrecognized "brain cholinergic antiinflammatory pathway" ) [1].There are show that the rapid activation cholinergic antiinflammatory pathway can protect against the hemorrhagic shock[2,3].

  13. The role of the central ghrelin system in reward from food and chemical drugs

    OpenAIRE

    Dickson, Suzanne L; Egecioglu, Emil; Landgren, Sara; Skibicka, Karolina P; Engel, Jörgen A; Jerlhag, Elisabet

    2011-01-01

    Abstract Here we review recent advances that identify a role for the central ghrelin signalling system in reward from both natural rewards (such as food) and artificial rewards (that include alcohol and drugs of abuse). Whereas ghrelin emerged as a stomach-derived hormone involved in energy balance, hunger and meal initiation via hypothalamic circuits, it now seems clear that it also has a role in motivated reward-driven behaviours via activation of the so-called ?cholinergic-dopam...

  14. INTEGRATING GEOPHYSICS, GEOLOGY, AND HYDROLOGY TO DETERMINE BEDROCK GEOMETRY CONTROLS ON THE ORIGIN OF ISOLATED MEADOW COMPLEXES WITHIN THE CENTRAL GREAT BASIN, NEVADA

    Science.gov (United States)

    Riparian meadow complexes found in mountain ranges of the Central Great Basin physiographic region (western United States) are of interest to researchers as they contain significant biodiversity relative to the surrounding basin areas. These meadow complexes are currently degradi...

  15. Altitude acclimatization improves submaximal cognitive performance in mice and involves an imbalance of the cholinergic system.

    Science.gov (United States)

    Guerra-Narbona, R; Delgado-García, J M; López-Ramos, J C

    2013-06-15

    The aim of this work was to reveal a hypothetical improvement of cognitive abilities in animals acclimatized to altitude and performing under ground level conditions, when looking at submaximal performance, once seen that it was not possible when looking at maximal scores. We modified contrasted cognitive tasks (object recognition, operant conditioning, eight-arm radial maze, and classical conditioning of the eyeblink reflex), increasing their complexity in an attempt to find performance differences in acclimatized animals vs. untrained controls. In addition, we studied, through immunohistochemical quantification, the expression of choline acetyltransferase and acetyl cholinesterase, enzymes involved in the synthesis and degradation of acetylcholine, in the septal area, piriform and visual cortexes, and the hippocampal CA1 area of animals submitted to acute hypobaric hypoxia, or acclimatized to this simulated altitude, to find a relationship between the cholinergic system and a cognitive improvement due to altitude acclimatization. Results showed subtle improvements of the cognitive capabilities of acclimatized animals in all of the tasks when performed under ground-level conditions (although not before 24 h), in the three tasks used to test explicit memory (object recognition, operant conditioning in the Skinner box, and eight-arm radial maze) and (from the first conditioning session) in the classical conditioning task used to evaluate implicit memory. An imbalance of choline acetyltransferase/acetyl cholinesterase expression was found in acclimatized animals, mainly 24 h after the acclimatization period. In conclusion, altitude acclimatization improves cognitive capabilities, in a process parallel to an imbalance of the cholinergic system. PMID:23599398

  16. Cholinergic neuronal differentiation of bone marrow mesenchymal stem cells in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The purpose of the present study was to determine the best cholinergic neuronal differentiation method of rhesus monkey bone marrow mesenchymal stem cells(BMSCs).Four methods were used to induce differentiation,and the groups were assigned accordingly:basal inducing group(culture media,bFGF,and forskolin);SHH inducing group(SHH,inducing group);RA inducing group(RA,basal inducing group);and SHH+RA inducing group(SHH,RA,and basal inducing group).All groups displayed neuronal morphology and increased expression of nestin and neuron-specific enolase.The basal inducing group did not express synapsin,and cells from the SHH inducing group did not exhibit neuronal resting membrane potential.In contrast,results demonstrated that BMSCs from the RA and SHH+RA inducing groups exhibited neuronal resting membrane potential,and cells from the SHH+RA inducing group expressed higher levels of synapsin and acetylcholine.In conclusion,the induction of cholinergic differentiation through SHH+RA was determined to be superior to the other methods.

  17. Preclinical Evidence for a Role of the Nicotinic Cholinergic System in Parkinson's Disease.

    Science.gov (United States)

    Perez, Xiomara A

    2015-12-01

    One of the primary deficits in Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra pars compacta which leads to striatal dopaminergic deficits that underlie the motor symptoms associated with the disease. A plethora of animal models have been developed over the years to uncover the molecular alterations that lead to PD development. These models have provided valuable information on neurotransmitter pathways and mechanisms involved. One such a system is the nicotinic cholinergic system. Numerous studies show that nigrostriatal damage affects nicotinic receptor-mediated dopaminergic signaling; therefore therapeutic modulation of the nicotinic cholinergic system may offer a novel approach to manage PD. In fact, there is evidence showing that nicotinic receptor drugs may be useful as neuroprotective agents to prevent Parkinson's disease progression. Additional preclinical studies also show that nicotinic receptor drugs may be beneficial for the treatment of L-dopa induced dyskinesias. Here, we review preclinical findings supporting the idea that nicotinic receptors are valuable therapeutic targets for PD. PMID:26553323

  18. Outcomes from two forms of training for first-responder competency in cholinergic crisis management.

    Science.gov (United States)

    Andreatta, Pamela; Klotz, Jessica J; Madsen, James M; Hurst, Charles G; Talbot, Thomas B

    2015-04-01

    Military and civilian first responders must be able to recognize and effectively manage mass disaster casualties. Clinical management of injuries resulting from nerve agents provides different challenges for first responders than those of conventional weapons. We evaluated the impact of a mixed-methods training program on competency acquisition in cholinergic crisis clinical management using multimedia with either live animal or patient actor examples, and hands-on practice using SimMan3G mannequin simulators. A purposively selected sample of 204 civilian and military first responders who had not previously completed nerve agent training were assessed pre- and post-training for knowledge, performance, self-efficacy, and affective state. We conducted analysis of variance with repeated measures; statistical significance p 20%, performance > 50%, self-efficacy > 34%, and affective state > 15%. There were no significant differences between the live animal and patient actor groups. These findings could aid in the specification of training for first-responder personnel in military and civilian service. Although less comprehensive than U.S. Army Medical Research Institute of Chemical Defense courses, the training outcomes associated with this easily distributed program demonstrate its value in increasing the competency of first responders in recognizing and managing a mass casualty cholinergic event.

  19. Acetylcholine released from cholinergic nerves contributes to cutaneous vasodilation during heat stress

    Science.gov (United States)

    Shibasaki, Manabu; Wilson, Thad E.; Cui, Jian; Crandall, Craig G.

    2002-01-01

    Nitric oxide (NO) contributes to active cutaneous vasodilation during a heat stress in humans. Given that acetylcholine is released from cholinergic nerves during whole body heating, coupled with evidence that acetylcholine causes vasodilation via NO mechanisms, it is possible that release of acetylcholine in the dermal space contributes to cutaneous vasodilation during a heat stress. To test this hypothesis, in seven subjects skin blood flow (SkBF) and sweat rate were simultaneously monitored over three microdialysis membranes placed in the dermal space of dorsal forearm skin. One membrane was perfused with the acetylcholinesterase inhibitor neostigmine (10 microM), the second membrane was perfused with the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME; 10 mM) dissolved in the aforementioned neostigmine solution (l-NAME(Neo)), and the third membrane was perfused with Ringer solution as a control site. Each subject was exposed to approximately 20 min of whole body heating via a water-perfused suit, which increased mean body temperature from 36.4 +/- 0.1 to 37.5 +/- 0.1 degrees C (P acetylcholine released from cholinergic nerves is capable of modulating cutaneous vasodilation via NO synthase mechanisms early in the heat stress but not after substantial cutaneous vasodilation.

  20. Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment

    Directory of Open Access Journals (Sweden)

    Saswati ePaul

    2015-04-01

    Full Text Available A substantial number of studies on basal forebrain cholinergic neurons (BFCN have provided compelling evidence for their role in the etiology of stress, cognitive aging, Alzheimer’s disease (AD, and other neurodegenerative diseases. BFCN project to a broad range of cortical sites and limbic structures, including the hippocampus, and are involved in stress and cognition. In particular, the hippocampus, the primary target tissue of the glucocorticoid stress hormones, is associated with cognitive function in tandem with hypothalamic-pituitary-adrenal (HPA axis modulation. The present review summarizes glucocorticoid and HPA axis research to date in an effort to establish the manner in which stress affects the release of acetylcholine, glucocorticoids, and their receptor in the context of cognitive processes. We attempt to provide the molecular interactive link between the glucocorticoids and cholinergic system that contributes to BFCN degeneration in stress-induced acceleration of cognitive decline in aging and AD. We also discuss the importance of animal models in facilitating such studies for pharmacological use, which could help decipher disease states and propose leads for pharmacological intervention.

  1. Antagonist of the amylin receptor blocks beta-amyloid toxicity in rat cholinergic basal forebrain neurons.

    Science.gov (United States)

    Jhamandas, Jack H; MacTavish, David

    2004-06-16

    Salvage of cholinergic neurons in the brain through a blockade of the neurotoxic effects of amyloidbeta protein (Abeta) is one of the major, but still elusive, therapeutic goals of current research in Alzheimer's disease (AD). To date, no receptor has been unequivocally identified for Abeta. Human amylin, which acts via a receptor composed of the calcitonin receptor-like receptor and a receptor-associated membrane protein, possesses amyloidogenic properties and has a profile of neurotoxicity that is strikingly similar to Abeta. In this study, using primary cultures of rat cholinergic basal forebrain neurons, we show that acetyl-[Asn30, Tyr32] sCT(8-37) (AC187), an amylin receptor antagonist, blocks Abeta-induced neurotoxicity. Treatment of cultures with AC187 before exposure to Abeta results in significantly improved neuronal survival as judged by MTT and live-dead cell assays. Quantitative measures of Abeta-evoked apoptotic cell death, using Hoechst and phosphotidylserine staining, confirm neuroprotective effects of AC187. We also demonstrate that AC187 attenuates the activation of initiator and effector caspases that mediate Abeta-induced apoptotic cell death. These data are the first to show that expression of Abeta toxicity may occur through the amylin receptor and suggest a novel therapeutic target for the treatment of AD. PMID:15201330

  2. Hypothesis for synergistic toxicity of organophosphorus poisoning-induced cholinergic crisis and anaphylactoid reactions

    Energy Technology Data Exchange (ETDEWEB)

    Cowan, F.M.; Shih, T.M.; Lenz, D.E.; Madsen, J.M.; Broomfield, C.A.

    1996-08-01

    The neurotoxicity of organophosphorus (OP) compounds Involves the Inhibition of acetylchollnesterase (AChE), causing accumulation of acetyicholine (ACh) at synapses. However, cholinergic crisis may not be the sole mechanism of OP toxicity. Adverse drug reactions caused by synergistic toxicity between drugs with distinct pharmacological mechanisms are a common problem. Likewise, the multiple pharmacological activities of a single molecule might also contribute to either toxicity or efficacy. For example, certain OP compounds (e.g. soman) exhibit anti-AChE activity and also act as secretagogues by inducing mast cell degranulation with associated autacoid release and anaphylactoid reactions. Anaphylactoid shock can produce a lethal syndrome with symptoms of respiratory failure and circulatory collapse similar to the physiological sequelae observed for OP poisoning. Moreover, the major classes of drugs used as antidotes for OP intoxication can affect anaphylaxis. Acetylcholine can act as an agonist of autacoid release, and autacoids such as histamine can augment soman-Induced bronchial spasm. In concert with the demonstrably critical role of cholinergic crisis In OP toxicity, the precepts of neuroimmunology indicate that secondary adverse reactions encompassing anaphylactold reactions may complicate OP toxicity.

  3. Outsourcing central banking

    DEFF Research Database (Denmark)

    Khoury, Sarkis Joseph; Wihlborg, Clas

    2005-01-01

    The literature on Currency Boards (CB) stops at the water edge in terms of dealing with the totality of the functions of a central bank. Monetary policy, and banking supervisioncan be "outsourced" in an open economy with substantial foreign direct investment (FDI)in the banking sector if political...... the feasibility of, and constraints on, outsourcing of central bank functions. A brief discussion of the Argentinian experience is used for contrast.Key words: Currency Board, Foreign Banks, Supervision, Regional Integration,outsourcing....

  4. Subtle learning and memory impairment in an idiopathic rat model of Alzheimer's disease utilizing cholinergic depletions and β-amyloid.

    Science.gov (United States)

    Deibel, S H; Weishaupt, N; Regis, A M; Hong, N S; Keeley, R J; Balog, R J; Bye, C M; Himmler, S M; Whitehead, S N; McDonald, R J

    2016-09-01

    Alzheimer's disease (AD) is a disease of complex etiology, involving multiple risk factors. When these risk factors are presented concomitantly, cognition and brain pathology are more severely compromised than if those risk factors were presented in isolation. Reduced cholinergic tone and elevated amyloid-beta (Aβ) load are pathological hallmarks of AD. The present study sought to investigate brain pathology and alterations in learning and memory when these two factors were presented together in rats. Rats received either sham surgeries, cholinergic depletions of the medial septum, intracerebroventricular Aβ25-35 injections, or both cholinergic depletion and Aβ25-35 injections (Aβ+ACh group). The Aβ+ACh rats were unimpaired in a striatal dependent visual discrimination task, but had impaired acquisition in the standard version of the Morris water task. However, these rats displayed normal Morris water task retention and no impairment in acquisition of a novel platform location during a single massed training session. Aβ+ACh rats did not have exacerbated brain pathology as indicated by activated astroglia, activated microglia, or accumulation of Aβ. These data suggest that cholinergic depletions and Aβ injections elicit subtle cognitive deficits when behavioural testing is conducted shortly after the presentation of these factors. These factors might have altered hippocampal synaptic plasticity and thus resemble early AD pathology. PMID:27208489

  5. Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2014-01-01

    Full Text Available To date, the effective preventive paradigm against mild cognitive impairment (MCI is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv. At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism.

  6. The Role of Muscarinic and Nicotinic Cholinergic Neurotransmission in Aversive Conditioning: Comparing Pavlovian Fear Conditioning and Inhibitory Avoidance

    Science.gov (United States)

    Tinsley, Matthew R.; Quinn, Jennifer J.; Fanselow, Michael S.

    2004-01-01

    Aversive conditioning is an ideal model for studying cholinergic effects on the processes of learning and memory for several reasons. First, deficits produced by selective lesions of the anatomical structures shown to be critical for Pavlovian fear conditioning and inhibitory avoidance (such as the amygdala and hippocampus) resemble those deficits…

  7. Dorsal raphe nucleus acetylcholine-mediated neurotransmission modulates post-ictal antinociception: The role of muscarinic and nicotinic cholinergic receptors.

    Science.gov (United States)

    de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Biagioni, Audrey Francisco; Falconi-Sobrinho, Luiz Luciano; Coimbra, Norberto Cysne

    2016-01-15

    The dorsal raphe nucleus (DRN) is a key structure of the endogenous pain inhibitory system. Although the DRN is rich in serotoninergic neurons, cholinergic neurons are also found in that nucleus. Both ictal and inter-ictal states are followed by post-ictal analgesia. The present study investigated the role of cholinergic mechanisms in postictal antinociceptive processes using microinjections of atropine and mecamylamine, muscarinic and nicotinic cholinergic receptor antagonists, respectively, in the DRN of rats. Intraperitoneal injection of pentylenetetrazole (PTZ) (at 64mg/kg) caused tonic and tonic-clonic seizures. The convulsive motor reactions were followed by an increase in pain thresholds, a phenomenon known as post-ictal analgesia. Pre-treatment of the DRN with atropine or mecamylamine at 1µg, 3µg and 5µg/0.2µL decreased the post-ictal antinociceptive phenomenon. The present results showed that the post-ictal analgesia was mediated by muscarinic and nicotinic cholinergic receptors in the DRN, a structure crucially involved in the neural network that organises post-ictal hypoalgesia. PMID:26620541

  8. Role of cholinergic anti-inflammatory pathway in regulating host response and its interventional strategy for inflammatory diseases

    Institute of Scientific and Technical Information of China (English)

    WANG Da-wei; ZHOU Rong-bin; YAO Yong-ming

    2009-01-01

    @@ The cholinergic anti-inflammatory pathway (CAP) is a neurophysiological mechanism that regulates the immune system. The CAP inhibits inflammation by suppressing cytokine synthesis via release of acetylcholine in organs of the reticuloendothelial system, including the lungs, spleen, liver, kidneys and gastrointestinal tract.

  9. Effect of corticosterone and adrenalectomy on NMDA-induced cholinergic cell death in rat magnocellular nucleus basalis

    NARCIS (Netherlands)

    Abraham, [No Value; Veenema, AH; Nyakas, C; Harkany, T; Bohus, BGJ; Luiten, PGM; Ábrahám, I.

    1997-01-01

    The present study demonstrates the effects of adrenalectomy and subcutaneously administered corticosterone on N-methyl-D-aspartate-induced neurodegeneration in the cholinergic magnocellular basal nucleus of the rat, NMDA was unilaterally injected into the nucleus basalis at different plasma corticos

  10. Change of cholinergic transmission and memory deficiency induced by injection of b-amyloid protein into NBM of rats

    Institute of Scientific and Technical Information of China (English)

    马晓峰; 叶惟泠; 梅镇彤

    2001-01-01

    The change of cholinergic transmission of b-amyloid protein (b-AP) treated rats was studied by intracerebral microdialysis sampling combined with HPLC analysis. b-AP1-40 was injected into nucleus basalis magnocellularis (NBM). Passive avoidance response test (step-down test) and delayed alternation task were used for memory testing. The impairment of memory after injection of b-AP1-40 into NBM exhibited mainly the deficiency of short-term working memory. One week after injection of b-AP1-40 the release of acetylcholine (ACh) from frontal cortex of freely-moving rats decreased significantly, and the response of cholinergic nerve ending to the action of high [K+] solution was rather weak. In control animals the percentage of increase of ACh- release during behavioral performance was 57%, while in b-AP1-40 - treated rats it was 34%. The temporary in-crease of the ACh-release of the rat put into a new place was also significantly diminished in b-AP1-40 -treated rats. The results show that the injection of b-AP1-40 into NBM impairs the cholinergic transmission in frontal cortex, and the impairment of cholinergic transmission may be the main cause of the deficit of working memory.

  11. Culture density regulates both the cholinergic phenotype and the expression of the CNTF receptor in P19 neurons.

    Science.gov (United States)

    Parnas, D; Linial, M

    1997-04-01

    The P19 embryonal carcinoma cells differentiate into neurons, astrocytes, and fibroblast-like cells following induction with retinoic acid. The cells mature into functional neurons, as determined by their ability to release neurotransmitters in a Ca(2+)- and depolarization-dependent manner. P19 neurons in culture represent a mixed population in terms of their neurotransmitter phenotype. The cholinergic phenotype of these neurons is modulated by culture density. Cholinergic markers, such as the vesicular acetylcholine transporter, acetyl cholinesterase, and choline acetyltransferase, are expressed in about 85% of the cells in sparse cultures and are largely suppressed at high cell densities. In contrast, glutamate release is enhanced in dense P19 neuronal cultures. The factor mediating the density effect is concentrated exclusively on the cell membrane of P19 neurons and not on the nonneuronal cells, which also differentiate from P19 embryonal carcinoma cells. This membrane-associated component retains its functionality, even after membrane fixation. The downregulation of the cholinergic properties in dense cultures is paralleled by a downregulation of the alpha subunit of the ciliary neurotrophic factor (CNTF) receptor. Thus, it is suggested that the membrane-associated factor, which mediates the density effect, downregulates the cholinergic phenotype by inhibiting the responsiveness of these neurons to CNTF. We further suggest that the P19 cell line can serve as a model system for the study of neurotransmitter phenotype acquisition and plasticity throughout neuronal differentiation. PMID:9188041

  12. Cholinergic neurons and terminal fields revealed by immunohistochemistry for the vesicular acetylcholine transporter. II. The peripheral nervous system.

    Science.gov (United States)

    Schäfer, M K; Eiden, L E; Weihe, E

    1998-05-01

    The peripheral sympathetic and parasympathetic cholinergic innervation was investigated with antibodies directed against the C-terminus of the rat vesicular acetylcholine transporter. Immunohistochemistry for the vesicular acetylcholine transporter resulted in considerably more detailed visualization of cholinergic terminal fields in the peripheral nervous system than reported previously and was well suited to also identify cholinergic perikarya. Vesicular acetylcholine transporter immunoreactivity completely delineated the preganglionic sympathetic terminals in pre- and paravertebral sympathetic ganglia, and in the adrenal medulla as well as postganglionic cholinergic neurons in the paravertebral chain. Cholinergic terminals of sudomotor and vasomotor nerves of skeletal muscle were optimally visualized. Mixed peripheral ganglia, including periprostatic and uterovaginal ganglia, exhibited extensive preganglionic cholinergic innervation of both noradrenergic and cholinergic postganglionic principal neurons which were intermingled in these ganglia. Varicose vesicular acetylcholine transporter-positive fibres and terminals, representing the cranial parasympathetic innervation of the cerebral vasculature, of salivary and lacrimal glands, of the eye, of the respiratory tract and of the upper digestive tract innervated various target structures including seromucous gland epithelium and myoepithelium, respiratory epithelium, and smooth muscle of the tracheobronchial tree. The only macrovascular elements receiving vesicular acetylcholine transporter-positive innervation were the cerebral arteries. The microvasculature throughout the viscera, with the exception of lymphoid tissues, the liver and kidney, received vesicular acetylcholine transporter-positive innervation while the microvasculature of limb and trunk skeletal muscle appeared to be the only relevant somatic target of vesicular acetylcholine transporter innervation. Vesicular acetylcholine transporter

  13. A cholinergic-regulated circuit coordinates the maintenance and bi-stable states of a sensory-motor behavior during Caenorhabditis elegans male copulation.

    Directory of Open Access Journals (Sweden)

    Yishi Liu

    2011-03-01

    Full Text Available Penetration of a male copulatory organ into a suitable mate is a conserved and necessary behavioral step for most terrestrial matings; however, the detailed molecular and cellular mechanisms for this distinct social interaction have not been elucidated in any animal. During mating, the Caenorhabditis elegans male cloaca is maintained over the hermaphrodite's vulva as he attempts to insert his copulatory spicules. Rhythmic spicule thrusts cease when insertion is sensed. Circuit components consisting of sensory/motor neurons and sex muscles for these steps have been previously identified, but it was unclear how their outputs are integrated to generate a coordinated behavior pattern. Here, we show that cholinergic signaling between the cloacal sensory/motor neurons and the posterior sex muscles sustains genital contact between the sexes. Simultaneously, via gap junctions, signaling from these muscles is transmitted to the spicule muscles, thus coupling repeated spicule thrusts with vulval contact. To transit from rhythmic to sustained muscle contraction during penetration, the SPC sensory-motor neurons integrate the signal of spicule's position in the vulva with inputs from the hook and cloacal sensilla. The UNC-103 K(+ channel maintains a high excitability threshold in the circuit, so that sustained spicule muscle contraction is not stimulated by fewer inputs. We demonstrate that coordination of sensory inputs and motor outputs used to initiate, maintain, self-monitor, and complete an innate behavior is accomplished via the coupling of a few circuit components.

  14. Cholinergic receptors as target for cancer therapy in a systems medicine perspective.

    Science.gov (United States)

    Russo, P; Del Bufalo, A; Milic, M; Salinaro, G; Fini, M; Cesario, A

    2014-01-01

    Epithelial cells not innervated by cholinergic neurons express nicotinic and muscarinic acetylcholine (ACh) receptors (nAChR, mAChR). nAChR and mAChR are components of the auto-/paracrine-regulatory loop of non-neuronal ACh release. The cholinergic control of non-neuronal cells may be mediated by different effects (synergistic, additive, or reciprocal) triggered by these receptors. The ionic events (Ca(+2) influx) are generated by the ACh-opening of nAChR channels, while the metabolic events by ACh-binding to G-proteincoupled mAChR. Effective inter- and intracellular signaling is crucial for valuable cancer cells proliferation and survival. Depending on cancer cell type, different AChR have been identified. The proliferation of airways epithelial cancer cells and pancreatic cancer cells may be under the control of α7-nAChR and M3-mAChR, while breast cancer cells and colon cancer cells are regulated by α9-nAChR, and M3-mAChR, respectively. In turn, these receptors may activate different pathways (Ras-Raf-1-Erk-AKT) as well as other receptors (β- adrenergicR). nAChR or mAChR antagonists may inhibit cancer growth. Inhibition of M3 by antisense or antagonists (Darifenacin, Tiotropium) reduces lung or colon cancer proliferation, as well as inhibition of α9- nAChR [polyphenol (-)-epigallocatechin-3-gallate] diminishes breast cancer cells growth. α7-nAChR silencing inhibits lung cancer proliferation. Moreover, inhibition of the nAChR-β-adrenergicR pathway (β-blockers) could be also useful. This review will describe the future translational perspectives of cholinergic receptors druginhibition in a complex disease such as cancer that poses compelling treatment challenges. Cancer happens as consequence of disease-perturbed molecular networks in relevant organ cells that change during progression. The framework for approaching these challenges is a systems approach. PMID:25324001

  15. Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

    Science.gov (United States)

    Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla

    2016-04-01

    Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD. PMID:26638718

  16. A Cross Country Analysis of Curricular Reform in Vocational Education and Training in Central and Eastern Europe. Integration of Work and Learning. Report.

    Science.gov (United States)

    Parkes, David, Ed.; Gronwald, Detlef; Grootings, Peter; Nielsen, Soren

    Curriculum reform in vocational education and training (VET) in Central and Eastern Europe was examined through case studies of VET in 10 countries: Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovak Republic, and Slovenia. Special attention was paid to the following: each country's VET system; curriculum…

  17. Cuidados com cateter central de inserção periférica no neonato: revisão integrativa da literatura Cuidados con catéter central de inserción periférica en el neonato: revisión integrativa de la literatura Peripherally inserted central catheter care in neonates: an integrative literature review

    Directory of Open Access Journals (Sweden)

    Derdried Athanasio Johann

    2012-12-01

    Full Text Available O cateter central de inserção periférica é tecnologia comum empregada na terapia intravenosa de neonatos. Trata-se de revisão integrativa, cujo objetivo foi investigar e analisar as evidências disponíveis na literatura acerca da temática. As bases de dados pesquisadas foram Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS e Biblioteca Nacional de Medicina dos Estados Unidos (PubMed. Resultados apontam lacunas no que tange à população neonatal; conhecimento insuficiente dos profissionais quanto indicações (n=1; e variados temas sobre uso de anticoagulantes (n=6, comparação com outros cateteres (n=4, diagnóstico por imagem (n=2, dor (n=2, infecção relacionada a cateter e sua prevenção (n=7, entre outros fatores. Conclui-se que há necessidade de atualização profissional, evidências científicas de fácil acesso e publicações nacionais.El catéter central de inserción periférica es una tecnología común empleada en terapia endovenosa de neonatos. Se trata de una revisión integrativa, cuyo objetivo fue investigar y analizar las evidencias disponibles en la literatura acerca de la temática. Se investigaron las bases de datos Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS y la Biblioteca Nacional de Medicina de los Estados Unidos (PubMed. Los resultados expresan omisiones en lo referente a la población neonatal; conocimiento insuficiente de los profesionales al respecto de las indicaciones (n=1, diagnóstico por imagen (n=2, dolor (n=2, infección relacionada al catéter y su prevención (n=7, entre otras. Se necesita de actualización profesional; evidencias científicas de fácil acceso y publicaciones nacionales.The peripherally inserted central catheter is a common technology employed in the intravenous therapy of neonates. This integrative review was performed with the objective to investigate and analyze the evidence available in the literature regarding this

  18. Effects of mescaline and some of its analogs on cholinergic neuromuscular transmission.

    Science.gov (United States)

    Ghansah, E; Kopsombut, P; Malleque, M A; Brossi, A

    1993-02-01

    Mescaline (3,4,5-trimethoxyphenylethylamine; MES) and its analogs, anhalinine (ANH) and methylenemescaline trimer (MMT) were investigated, using sciatic-sartorius preparations of the frog and cortical tissue from the rat. The effects of MES and its analogs were examined with respect to muscle twitch, resting membrane potential and nicotinic receptor binding. Mescaline and its analogs (10-100 microM) blocked both directly and neurally evoked twitches but their effects on neurally evoked twitches were greater than those on directly evoked twitches. Mescaline, ANH and MMT decreased amplitude of the miniature endplate and endplate potentials, decreased acetylcholine (ACh) quantal content, hyperpolarized the resting membrane potential and prolonged duration of the action potential. They did not significantly displace the binding of [125I]-alpha-bungarotoxin (alpha-BTX) to nicotinic receptors, at concentrations which blocked neuromuscular transmission. These results suggest that MES and its analogs inhibit cholinergic neuromuscular transmission by blocking release of ACh; they also affect K+ conductance.

  19. A cholinergic contribution to the circulatory responses evoked at the onset of handgrip exercise in humans

    DEFF Research Database (Denmark)

    Vianna, Lauro C; Fadel, Paul J; Secher, Niels H;

    2015-01-01

    of the muscle is relatively small compared with the onset of leg cycling, where a marked increase in muscle blood flow rapidly occurs as a consequence of multiple redundant mechanisms. We recorded blood pressure (BP; brachial artery), stroke volume (pulse contour analysis), cardiac output, and systemic vascular...... resistance (SVR) in young healthy males, while performing either 20 s of isometric handgrip contraction at 40% maximum voluntary contraction (protocol 1; n = 9) or 20 s of low-intensity leg cycling exercise (protocol 2; n = 8, 42 ± 8 W). Exercise trials were conducted under control (no drug) conditions...... and following cholinergic blockade (glycopyrrolate). Under control conditions, isometric handgrip elicited an initial increase in BP (+5 ± 2 mmHg at 3 s and +3 ± 1 mmHg at 10 s, P

  20. GRK5 Deficiency Leads to Selective Basal Forebrain Cholinergic Neuronal Vulnerability.

    Science.gov (United States)

    He, Minchao; Singh, Prabhakar; Cheng, Shaowu; Zhang, Qiang; Peng, Wei; Ding, XueFeng; Li, Longxuan; Liu, Jun; Premont, Richard T; Morgan, Dave; Burns, Jeffery M; Swerdlow, Russell H; Suo, William Z

    2016-05-19

    Why certain diseases primarily affect one specific neuronal subtype rather than another is a puzzle whose solution underlies the development of specific therapies. Selective basal forebrain cholinergic (BFC) neurodegeneration participates in cognitive impairment in Alzheimer's disease (AD), yet the underlying mechanism remains elusive. Here, we report the first recapitulation of the selective BFC neuronal loss that is typical of human AD in a mouse model termed GAP. We created GAP mice by crossing Tg2576 mice that over-express the Swedish mutant human β-amyloid precursor protein gene with G protein-coupled receptor kinase-5 (GRK5) knockout mice. This doubly defective mouse displayed significant BFC neuronal loss at 18 months of age, which was not observed in either of the singly defective parent strains or in the wild type. Along with other supporting evidence, we propose that GRK5 deficiency selectively renders BFC neurons more vulnerable to degeneration.

  1. Cholinergic stimulation of pancreatic amylase release and muscarinic receptors: effect of ionophore A23187

    International Nuclear Information System (INIS)

    Dispersed rat pancreatic acini were incubated in 0.5 mM calcium medium with increasing concentrations of carbamylcholine, with or without the ionophore A23187 (10-6M). Addition of the ionophore reduced maximal amylase release, increased the maximal effective concentration of carbamylcholine and dramatically impaired the agonist's capacity to induce enzyme secretion at low concentration. The ionophore also abolished the inhibition of secretion observed at high carbamylcholine concentrations. These effects of the ionophore on the cholinergic secretory response cannot be explained by interaction at the muscarinic receptor since neither the Bmax, the affinity of the receptor for the [3H]QNB nor the binding of carbamylcholine were affected by the ionophore. It is suggested that for the conditions studied, the ionophore can interact with the secretory process at one or several points ulterior to the initial recognition site of carbamylcholine on its receptor. 30 references, 3 figures

  2. Striatal Cholinergic Interneurons Control Motor Behavior and Basal Ganglia Function in Experimental Parkinsonism.

    Science.gov (United States)

    Maurice, Nicolas; Liberge, Martine; Jaouen, Florence; Ztaou, Samira; Hanini, Marwa; Camon, Jeremy; Deisseroth, Karl; Amalric, Marianne; Kerkerian-Le Goff, Lydia; Beurrier, Corinne

    2015-10-27

    Despite evidence showing that anticholinergic drugs are of clinical relevance in Parkinson's disease (PD), the causal role of striatal cholinergic interneurons (CINs) in PD pathophysiology remains elusive. Here, we show that optogenetic inhibition of CINs alleviates motor deficits in PD mouse models, providing direct demonstration for their implication in parkinsonian motor dysfunctions. As neural correlates, CIN inhibition in parkinsonian mice differentially impacts the excitability of striatal D1 and D2 medium spiny neurons, normalizes pathological bursting activity in the main basal ganglia output structure, and increases the functional weight of the direct striatonigral pathway in cortical information processing. By contrast, CIN inhibition in non-lesioned mice does not affect locomotor activity, equally modulates medium spiny neuron excitability, and does not modify spontaneous or cortically driven activity in the basal ganglia output, suggesting that the role of these interneurons in motor function is highly dependent on dopamine tone. PMID:26489458

  3. Striatal Cholinergic Interneurons Control Motor Behavior and Basal Ganglia Function in Experimental Parkinsonism

    Directory of Open Access Journals (Sweden)

    Nicolas Maurice

    2015-10-01

    Full Text Available Despite evidence showing that anticholinergic drugs are of clinical relevance in Parkinson’s disease (PD, the causal role of striatal cholinergic interneurons (CINs in PD pathophysiology remains elusive. Here, we show that optogenetic inhibition of CINs alleviates motor deficits in PD mouse models, providing direct demonstration for their implication in parkinsonian motor dysfunctions. As neural correlates, CIN inhibition in parkinsonian mice differentially impacts the excitability of striatal D1 and D2 medium spiny neurons, normalizes pathological bursting activity in the main basal ganglia output structure, and increases the functional weight of the direct striatonigral pathway in cortical information processing. By contrast, CIN inhibition in non-lesioned mice does not affect locomotor activity, equally modulates medium spiny neuron excitability, and does not modify spontaneous or cortically driven activity in the basal ganglia output, suggesting that the role of these interneurons in motor function is highly dependent on dopamine tone.

  4. 欧亚经济共同体对中亚区域一体化影响的研究%Study of the Influence of Eurasian Economic Community on the Integration of Central Asian Countries

    Institute of Scientific and Technical Information of China (English)

    王维然; 赵凤莲

    2012-01-01

    The central Asian countries have taken part in lots of regional economic cooperation organizations since the disintegration of the Soviet Union. It is uncertain whether these organizations, especially the most successful Eurasian Economic Community, have promoted the integration degree of these countries. The research results of this paper indicate that the participation of regional integration is beneficial for the exPort of central Asian countries, but the members of Eurasian Economic Community have not achieved their expected goals. The main cause lies in the fault of industrial structure in these countries. A trade integration network based on marketization has been gradually formed in central Asia, but the government of each country has not recognized its importance and positivity.%自独立以来,中亚国家组织和参加了多个区域经济合作组织。但这些组织.包括其中最为成功的欧亚经济共同体,是否提升了各国一体化水平却尚无定论。通过研究认为参与一体化对中亚国家出口的增长是有利的,但欧亚经济共同体却并未发挥各国预期的作用。产生问题的原因主要是各成员国经济发展水平不一、产业结构的缺陷和市场化程度低下。目前中亚已初步形成了基于市场化的贸易一体化网络并取得了良好的效果,但各国政府尚未认识到其作用和积极性。

  5. Diverse roles of neurotensin agonists in the central nervous system

    Directory of Open Access Journals (Sweden)

    Mona eBoules

    2013-03-01

    Full Text Available NT is a tridecapeptide that is found in the central nervous system and the gastrointestinal tract. NT behaves as a neurotransmitter in the brain and as a hormone in the gut. Additionally, NT acts as a neuromodulator to several neurotransmitter systems including dopaminergic, sertonergic, GABAergic, glutamatergic and cholinergic systems. Due to its association with such a wide variety of neurotransmitters, NT has been implicated in the pathophysiology of several central nervous system (CNS disorders such as schizophrenia, drug abuse, Parkinson’s disease, pain, central control of blood pressure, eating disorders, as well as, cancer and inflammation. The present review will focus on the role that NT and its analogs play in schizophrenia, endocrine function, pain, psychostimulant abuse, and Parkinson’s disease.

  6. Glucocorticoid-cholinergic interactions in the dorsal striatum in memory consolidation of inhibitory avoidance training

    Directory of Open Access Journals (Sweden)

    Oscar eSanchez-Resendis

    2012-06-01

    Full Text Available Extensive evidence indicates that glucocorticoid hormones act in a variety of brain regions to enhance the consolidation of memory of emotionally motivated training experiences. We previously reported that corticosterone, the major glucocorticoid in the rat, administered into the dorsal striatum immediately after inhibitory avoidance training dose-dependently enhances memory consolidation of this training. There is also abundant evidence that the intrinsic cholinergic system of the dorsal striatum is importantly involved in memory consolidation of inhibitory avoidance training. However, it is presently unknown whether these two neuromodulatory systems interact within the dorsal striatum in the formation of long-term memory. To address this issue, we first investigated in male Wistar rats whether the muscarinic receptor agonist oxotremorine administered into the dorsal striatum immediately after inhibitory avoidance training enhances 48-h retention of the training. Subsequently, we examined whether an attenuation of glucocorticoid signaling by either a systemic administration of the corticosterone-synthesis inhibitor metyrapone or an intra-striatal infusion of the glucocorticoid receptor antagonist RU 38486 would block the memory enhancement induced by oxotremorine. Our findings indicate that oxotremorine dose-dependently enhanced 48-h retention latencies, but that the administration of either metyrapone or RU 38486 prevented the memory-enhancing effect of oxotremorine. In the last experiment, corticosterone was infused into the dorsal striatum together with the muscarinic receptor antagonist scopolamine immediately after inhibitory avoidance training. Scopolamine blocked the enhancing effect of corticosterone on 48-h retention performance. These findings indicate that there are mutual interactions between glucocorticoids and the striatal cholinergic system in enhancing the consolidation of memory of inhibitory avoidance training.

  7. Treatment of Alzheimer's Disease: The Legacy of the Cholinergic Hypothesis, Neuroplasticity, and Future Directions.

    Science.gov (United States)

    Wesson Ashford, J

    2015-01-01

    In this issue, an article by Waring et al. provides a meta-analysis of the effects of apo-lipo-protein E (APOE) genotype on the beneficial effect of acetyl-cholinesterase inhibitors (AChEIs) in patients with Alzheimer's disease (AD). There was no significant effect found. As of 2015, AChEI medications are the mainstay of AD treatment, and APOE genotype is the most significant factor associated with AD causation. This lack of a significant effect of APOE is analyzed with respect to the "Cholinergic Hypothesis" of AD, dating from 1976, through the recognition that cholinergic neurons are not the sole target of AD, but rather that AD attacks all levels of neuroplasticity in the brain, an idea originated by Ashford and Jarvik in 1985 and which still provides the clearest explanation for AD dementia. The "Amyloid Hypothesis" is dissected back to the alpha/beta pathway switching mechanism affecting the nexin-amyloid pre-protein (NAPP switch). The NAPP switch may be the critical neuroplasticity component of all learning involving synapse remodeling and subserve all learning mechanisms. The gamma-secretase cleavage is discussed, and its normal complementary products, beta-amyloid and the NAPP intracellular domain (NAICD), appear to be involved in natural synapse removal, but the link to AD dementia may involve the NAICD rather than beta-amyloid. Understanding neuroplasticity and the critical pathways to AD dementia are needed to determine therapies and preventive strategies for AD. In particular, the effect of APOE on AD predisposition needs to be established and a means found to adjust its effect to prevent AD. PMID:26402763

  8. Effects of superoxide generating systems on muscle tone, cholinergic and NANC responses in cat airway.

    Science.gov (United States)

    Bauer, V; Nakajima, T; Pucovsky, V; Onoue, H; Ito, Y

    2000-02-14

    To study the possible role of reactive oxygen species in airway hyperreactivity, we examined the effects of the superoxide anion radical (O(2)(-)) generating systems, pyrogallol and xanthine with xanthine oxidase, on muscle tone, excitatory and inhibitory neurotransmission in the cat airway. Smooth muscle contraction or non-adrenergic non-cholinergic (NANC) relaxation evoked by electrical field stimulation (EFS) were measured before or after O(2)(-) generating systems with or without diethydithiocarbamic acid (DEDTCA), an inhibitor of endogenous superoxide dismutase (SOD). Resting membrane potential or excitatory junction potential (EJP) were also measured in vitro. Both pyrogallol and xanthine/xanthine oxidase produced biphasic changes in basal and elevated (by 5-HT) muscle tone. After SOD pretreatment, both systems consistently produced a prolonged contraction, thereby indicating that O(2)(-) was converted to H(2)O(2) by the action of SOD and as a result the actions of O(2)(-) were lost but those of H(2)O(2) introduced. The O(2)(-) showed no significant effect on smooth muscle contraction or EJP evoked by EFS, however after DEDTCA pretreatment, it evoked initial enhancement followed by suppression of the contraction and EJP. DEDTCA pretreatment ameliorated the inhibitory action of pyrogallol and xanthine/xanthine oxidase on the NANC relaxation, probably because O(2)(-) could combine with endogenous NO to form peroxynitrite. These results indicate that the O(2)(-) generating systems have multiple actions, presumably due to the presence and simultaneous action of at least two different reactive oxygen species (O(2)(-) and H(2)O(2)). While H(2)O(2) seems to be responsible for elevation of muscle tone and augmentation of smooth muscle contraction by EFS, O(2)(-) inhibits muscle tone, cholinergic and NANC neurotransmission.

  9. Hormonal Responses to Cholinergic Input Are Different in Humans with and without Type 2 Diabetes Mellitus

    Science.gov (United States)

    Dunai, Judit; Kilpatrick, Rachel; Oestricker, Lauren Z.; Wallendorf, Michael J.; Patterson, Bruce W.; Reeds, Dominic N.; Wice, Burton M.

    2016-01-01

    Peripheral muscarinic acetylcholine receptors regulate insulin and glucagon release in rodents but their importance for similar roles in humans is unclear. Bethanechol, an acetylcholine analogue that does not cross the blood-brain barrier, was used to examine the role of peripheral muscarinic signaling on glucose homeostasis in humans with normal glucose tolerance (NGT; n = 10), impaired glucose tolerance (IGT; n = 11), and type 2 diabetes mellitus (T2DM; n = 9). Subjects received four liquid meal tolerance tests, each with a different dose of oral bethanechol (0, 50, 100, or 150 mg) given 60 min before a meal containing acetaminophen. Plasma pancreatic polypeptide (PP), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), glucose, glucagon, C-peptide, and acetaminophen concentrations were measured. Insulin secretion rates (ISRs) were calculated from C-peptide levels. Acetaminophen and PP concentrations were surrogate markers for gastric emptying and cholinergic input to islets. The 150 mg dose of bethanechol increased the PP response 2-fold only in the IGT group, amplified GLP-1 release in the IGT and T2DM groups, and augmented the GIP response only in the NGT group. However, bethanechol did not alter ISRs or plasma glucose, glucagon, or acetaminophen concentrations in any group. Prior studies showed infusion of xenin-25, an intestinal peptide, delays gastric emptying and reduces GLP-1 release but not ISRs when normalized to plasma glucose levels. Analysis of archived plasma samples from this study showed xenin-25 amplified postprandial PP responses ~4-fold in subjects with NGT, IGT, and T2DM. Thus, increasing postprandial cholinergic input to islets augments insulin secretion in mice but not humans. Trial Registration: ClinicalTrials.gov NCT01434901 PMID:27304975

  10. Predominant Glandular Cholinergic Dysautonomia in Patients with Primary Sjögren’s Syndrome

    Science.gov (United States)

    Imrich, Richard; Alevizos, Ilias; Bebris, Lolita; Goldstein, David S.; Holmes, Courtney S.; Illei, Gabor G.; Nikolov, Nikolay P.

    2015-01-01

    Objectives The autonomic nervous system (ANS) modulates exocrine gland function. Available data show poor correlation between the degree of exocrine gland function and destruction in primary Sjögren’s syndrome (pSS) suggesting other mechanisms, such as autonomic dysfunction may be important in these patients. We performed a comprehensive analysis of sympathoneural and sympathetic cholinergic function in well-characterized patients with pSS. Methods 21 pSS patients (mean±SE age 44±3 years) and in 13 healthy controls (51±2 years) were assessed during orthostasis and intravenous injection of edrophonium (10 mg). The postganglionic sympathetic cholinergic system was evaluated by assessing sweat production by the quantitative sudomotor axon reflex test (QSART). Gastric empting testing assessed the gastro-intestinal ANS in pSS patients. Results Velocity index and acceleration index were significantly higher (p<0.05) in pSS compared to controls before and during the orthostatic and edrophonium tests. Other hemodynamic and neurochemical parameters did not differ between pSS patients and controls during the orthostasis and edrophonium test, however, edrophonium-induced saliva increment was lower in pSS (p=0.002). Abnormally low sweat production was found in four (N=4) pSS patients but in none of the controls in the QSART. Gastric empting was delayed in 53 % of pSS patients. Conclusion We observed subtle differences in several ANS domains, including gastrointestinal and sympathocholinergic system suggesting a complex ANS dysfunction in pSS. The impact was the largest on the exocrine glands with subtle differences in the cardiac parasympathetic function independent of glandular inflammation and atrophy, suggesting an alternative pathogenesis mechanism of the disease in pSS. PMID:25622919

  11. Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers.

    Directory of Open Access Journals (Sweden)

    H Scott Swartzwelder

    Full Text Available The long-term effects of intermittent ethanol exposure during adolescence (AIE are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational significance. Male rats (starting at PND-30 received exposure to AIE (5g/kg, i.g. or vehicle and were allowed to mature into adulthood. At PND-71, one group of animals was assessed using the spatial-temporal object recognition (stOR test to evaluate memory function. A separate group of animals was used to assess the density of cholinergic neurons in forebrain areas Ch1-4 using immunohistochemistry. AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4. These findings add to the growing literature indicating long-lasting neural and behavioral effects of AIE that persist into adulthood and indicate that memory-related deficits after AIE depend upon the tasks employed, and possibly their degree of complexity. Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE.

  12. VTA GABA neurons modulate specific learning behaviours through the control of dopamine and cholinergic systems

    Directory of Open Access Journals (Sweden)

    Meaghan C Creed

    2014-01-01

    Full Text Available The mesolimbic reward system is primarily comprised of the ventral tegmental area (VTA and the nucleus accumbens (NAc as well as their afferent and efferent connections. This circuitry is essential for learning about stimuli associated with motivationally-relevant outcomes. Moreover, addictive drugs affect and remodel this system, which may underlie their addictive properties. In addition to DA neurons, the VTA also contains approximately 30% ɣ-aminobutyric acid (GABA neurons. The task of signalling both rewarding and aversive events from the VTA to the NAc has mostly been ascribed to DA neurons and the role of GABA neurons has been largely neglected until recently. GABA neurons provide local inhibition of DA neurons and also long-range inhibition of projection regions, including the NAc. Here we review studies using a combination of in vivo and ex vivo electrophysiology, pharmacogenetic and optogenetic manipulations that have characterized the functional neuroanatomy of inhibitory circuits in the mesolimbic system, and describe how GABA neurons of the VTA regulate reward and aversion-related learning. We also discuss pharmacogenetic manipulation of this system with benzodiazepines (BDZs, a class of addictive drugs, which act directly on GABAA receptors located on GABA neurons of the VTA. The results gathered with each of these approaches suggest that VTA GABA neurons bi-directionally modulate activity of local DA neurons, underlying reward or aversion at the behavioural level. Conversely, long-range GABA projections from the VTA to the NAc selectively target cholinergic interneurons (CINs to pause their firing and temporarily reduce cholinergic tone in the NAc, which modulates associative learning. Further characterization of inhibitory circuit function within and beyond the VTA is needed in order to fully understand the function of the mesolimbic system under normal and pathological conditions.

  13. The α2-subunit of the nicotinic cholinergic receptor is specifically expressed in medial subpallium-derived cells of mammalian amygdala.

    Science.gov (United States)

    Pombero, Ana; Martinez, Salvador

    2015-08-01

    Nicotinic acetylcholine receptor (nAChR) subtypes are expressed in specific neuronal populations, which are involved in numerous neural functions such as sleep, fatigue, anxiety, and cognition, as well as the central processing of pain and food intake. Moreover, mutations in nAChRs subunits have been related to frontal lobe epilepsy, neurodegenerative diseases, and other neurological disorders, including schizophrenia and attention deficit and hyperactivity disorder (ADHD). Previous studies have shown that the α2-subunit of the AChR (Chrna2) is expressed in the basal forebrain, in the septum, and in some amygdalar nuclei in the adult rodent brain. However, although the importance of this amygdalar expression in emotion-related behavior and the physiopathology of neuropsychiatric disorders has been accepted, a detailed study of the Chrna2 expression pattern during development has been lacking. In this study we found that Chrna2 is specifically expressed in medial subpallium-derived amygdalar nuclei from early developmental stages to adult. This finding could help us to better understand the role of Chrna2 in the differentiation and functional maturation of amygdalar neurons involved in cholinergic-regulated emotional behavior. PMID:25641263

  14. Geometries of doleritic intrusions in central Spitsbergen, Svalbard: an integrated study of an onshore-offshore magmatic province with implications for CO2 sequestration

    OpenAIRE

    Senger, Kim; Roy, Srikumar; Braathen, Alvar; Buckley, Simon John; Bælum, Karoline; Gernigon, Laurent; Mjelde, Rolf; Noormets, Riko; Ogata, Kei; Olaussen, Snorre; Planke, Sverre; Ruud, Bent Ole; Tveranger, Jan

    2013-01-01

    Igneous intrusions emplaced during the Early Cretaceous are well exposed in central Spitsbergen within the Permian–Jurassic sedimentary succession. The doleritic intrusions are collectively classified as the Diabasodden Suite, and form part of the High Arctic Large Igneous Province. Though relatively easily accessible and very well exposed in places, the Diabasodden Suite dolerites remain underexplored and their prevalent geometry is particularly poorly understood. In this contribution ...

  15. From national to regional plans – the Integrated Drought Management Programme of the Global Water Partnership for Central and Eastern Europe

    OpenAIRE

    Sabina Bokal; Ania Grobicki; Janusz Kindler; Danka Thalmeinerova

    2014-01-01

    In the past few decades it has become evident that the countries of Central and Eastern Europe (CEE) are affected by droughts which are becoming more and more lasting and severe. The region׳s vulnerability to this natural hazard alerted the public, governments, and operational agencies to the many socio-economic problems accompanying water shortage and to the need for drought mitigation measures. In addition, climate change amplifies the frequency and severity of droughts in the region. In th...

  16. Central stress-integrative circuits: Forebrain glutamatergic and GABAergic projections to the dorsomedial hypothalamus, medial preoptic area, and bed nucleus of the stria terminalis

    OpenAIRE

    Myers, Brent; Dolgas, C. Mark; Kasckow, John; Cullinan, William E.; Herman, James P.

    2013-01-01

    Central regulation of hypothalamo-pituitary-adrenocortical (HPA) axis stress responses is mediated by a relatively circumscribed group of projections to the paraventricular hypothalamus (PVN). The dorsomedial hypothalamus (DMH), medial preoptic area (mPOA), and bed nucleus of the stria terminalis (BST) provide direct, predominantly inhibitory, innervation of the PVN. These PVN-projecting neurons are controlled by descending information from limbic forebrain structures, including the prefronta...

  17. Detection of Ca2+-dependent acid phosphatase activity identifies neuronal integrity in damaged rat central nervous system after application of bacterial melanin

    Directory of Open Access Journals (Sweden)

    Tigran R Petrosyan

    2016-01-01

    Full Text Available The study aims to confirm the neuroregenerative effects of bacterial melanin (BM on central nervous system injury using a special staining method based on the detection of Ca2+-dependent acid phosphatase activity. Twenty-four rats were randomly assigned to undergo either unilateral destruction of sensorimotor cortex (group I; n = 12 or unilateral rubrospinal tract transection at the cervical level (C3–4 (group II; n = 12. In each group, six rats were randomly selected after surgery to undergo intramuscular injection of BM solution (BM subgroup and the remaining six rats were intramuscularly injected with saline (saline subgroup. Neurological testing confirmed that BM accelerated the recovery of motor function in rats from both BM and saline subgroups. Two months after surgery, Ca2+-dependent acid phosphatase activity detection in combination with Chilingarian's calcium adenoside triphosphate method revealed that BM stimulated the sprouting of fibers and dilated the capillaries in the brain and spinal cord. These results suggest that BM can promote the recovery of motor function of rats with central nervous system injury; and detection of Ca2+-dependent acid phosphatase activity is a fast and easy method used to study the regeneration-promoting effects of BM on the injured central nervous system.

  18. Detection of Ca2+-dependent acid phosphatase activity identiifes neuronal integrity in damaged rat central nervous system after application of bacterial melanin

    Institute of Scientific and Technical Information of China (English)

    Tigran R Petrosyan; Anna S Ter-Markosyan; Anna S Hovsepyan

    2016-01-01

    The study aims to confirm the neuroregenerative effects of bacterial melanin (BM) on central nervous system injury using a special staining method based on the detection of Ca2+-dependent acid phosphatase activity. Twenty-four rats were randomly assigned to undergo either unilateral destruction of sensorimotor cortex (group I;n=12) or unilateral rubrospinal tract transection at the cervical level (C3–4) (group II;n=12). In each group, six rats were randomly selected after surgery to undergo intramuscular injection of BM solution (BM subgroup) and the remaining six rats were intramuscularly injected with saline (saline subgroup). Neurological testing confirmed that BM accelerated the recovery of motor function in rats from both BM and saline subgroups. Two months after surgery, Ca2+-dependent acid phosphatase activity detection in combination with Chilingarian’s calcium adenoside triphosphate method revealed that BM stimulated the sprouting of ifbers and dilated the capillaries in the brain and spinal cord. These results sug-gest that BM can promote the recovery of motor function of rats with central nervous system injury;and detection of Ca2+-dependent acid phosphatase activity is a fast and easy method used to study the regenera-tion-promoting effects of BM on the injured central nervous system.

  19. Detection of Ca(2+)-dependent acid phosphatase activity identifies neuronal integrity in damaged rat central nervous system after application of bacterial melanin.

    Science.gov (United States)

    Petrosyan, Tigran R; Ter-Markosyan, Anna S; Hovsepyan, Anna S

    2016-07-01

    The study aims to confirm the neuroregenerative effects of bacterial melanin (BM) on central nervous system injury using a special staining method based on the detection of Ca(2+)-dependent acid phosphatase activity. Twenty-four rats were randomly assigned to undergo either unilateral destruction of sensorimotor cortex (group I; n = 12) or unilateral rubrospinal tract transection at the cervical level (C3-4) (group II; n = 12). In each group, six rats were randomly selected after surgery to undergo intramuscular injection of BM solution (BM subgroup) and the remaining six rats were intramuscularly injected with saline (saline subgroup). Neurological testing confirmed that BM accelerated the recovery of motor function in rats from both BM and saline subgroups. Two months after surgery, Ca(2+)-dependent acid phosphatase activity detection in combination with Chilingarian's calcium adenoside triphosphate method revealed that BM stimulated the sprouting of fibers and dilated the capillaries in the brain and spinal cord. These results suggest that BM can promote the recovery of motor function of rats with central nervous system injury; and detection of Ca(2+)-dependent acid phosphatase activity is a fast and easy method used to study the regeneration-promoting effects of BM on the injured central nervous system. PMID:27630700

  20. Central Station Design Options

    DEFF Research Database (Denmark)

    2011-01-01

    The purpose of EDISON Work Package 4.1 is the evaluation of possible Central (charging) Stations design options for making possible the public charging of Electric Vehicles (EVs). A number of scenarios for EVs are assessed, with special emphasis on the options of Fast Charging and Battery Swapping....... The work identifies the architecture, sizing and siting of prospective Central Stations in Denmark, which can be located at shopping centers, large car parking lots or gas stations. Central Stations are planned to be integrated in the Danish distribution grid. The Danish island of Bornholm, where a high.......g. due to vandalism, the charge supply circuit is disconnected. More electrical vehicles on the market are capable today of quick charging up to 50 kW power level. The feasibility of Central Stations with fast charging/swapping option, their capacity, design, costs and grid impact, as well as battery...

  1. Critical role of cholinergic transmission from the laterodorsal tegmental nucleus to the ventral tegmental area in cocaine-induced place preference

    OpenAIRE

    Shinohara, Fumiya; Kihara, Yukari; Ide, Soichiro; Minami, Masabumi; Kaneda, Katsuyuki

    2014-01-01

    Conditioned place preference (CPP) is widely used to investigate the rewarding properties of cocaine. Various brain regions and neurotransmitters are involved in developing cocaine CPP. However, the contribution of cholinergic transmission in the ventral tegmental area (VTA) to cocaine CPP remains largely unexplored. Here, we examined the role of cholinergic input arising from the laterodorsal tegmental nucleus (LDT) to the VTA in the acquisition and expression of cocaine CPP in rats. Intra-L...

  2. Plant hydraulics as a central hub integrating plant and ecosystem function: meeting report for 'Emerging Frontiers in Plant Hydraulics' (Washington, DC, May 2015).

    Science.gov (United States)

    Sack, Lawren; Ball, Marilyn C; Brodersen, Craig; Davis, Stephen D; Des Marais, David L; Donovan, Lisa A; Givnish, Thomas J; Hacke, Uwe G; Huxman, Travis; Jansen, Steven; Jacobsen, Anna L; Johnson, Daniel M; Koch, George W; Maurel, Christophe; McCulloh, Katherine A; McDowell, Nate G; McElrone, Andrew; Meinzer, Frederick C; Melcher, Peter J; North, Gretchen; Pellegrini, Matteo; Pockman, William T; Pratt, R Brandon; Sala, Anna; Santiago, Louis S; Savage, Jessica A; Scoffoni, Christine; Sevanto, Sanna; Sperry, John; Tyerman, Stephen D; Way, Danielle; Holbrook, N Michele

    2016-09-01

    Water plays a central role in plant biology and the efficiency of water transport throughout the plant affects both photosynthetic rate and growth, an influence that scales up deterministically to the productivity of terrestrial ecosystems. Moreover, hydraulic traits mediate the ways in which plants interact with their abiotic and biotic environment. At landscape to global scale, plant hydraulic traits are important in describing the function of ecological communities and ecosystems. Plant hydraulics is increasingly recognized as a central hub within a network by which plant biology is connected to palaeobiology, agronomy, climatology, forestry, community and ecosystem ecology and earth-system science. Such grand challenges as anticipating and mitigating the impacts of climate change, and improving the security and sustainability of our food supply rely on our fundamental knowledge of how water behaves in the cells, tissues, organs, bodies and diverse communities of plants. A workshop, 'Emerging Frontiers in Plant Hydraulics' supported by the National Science Foundation, was held in Washington DC, 2015 to promote open discussion of new ideas, controversies regarding measurements and analyses, and especially, the potential for expansion of up-scaled and down-scaled inter-disciplinary research, and the strengthening of connections between plant hydraulic research, allied fields and global modelling efforts. PMID:27037757

  3. Integrated simulation of consumptive use and land subsidence in the Central Valley, California, for the past and for a future subject to urbanization and climate change

    Science.gov (United States)

    Hanson, Randall T.; Flint, Alan L.; Faunt, Claudia C.; Cayan, Daniel R.; Flint, Lorraine E.; Leake, Stanley A.; Schmid, Wolfgang

    2010-01-01

    Competition for water resources is growing throughout California, particularly in the Central Valley where about 20% of all groundwater used in the United States is consumed for agriculture and urban water supply. Continued agricultural use coupled with urban growth and potential climate change would result in continued depletion of groundwater storage and associated land subsidence throughout the Central Valley. For 1962-2003, an estimated 1,230 hectare meters (hm3) of water was withdrawn from fine-grained beds, resulting in more than three meters (m) of additional land subsidence locally. Linked physically-based, supply-constrained and emanddriven hydrologic models were used to simulate future hydrologic conditions under the A2 climate projection scenario that assumes continued "business as usual" greenhouse gas emissions. Results indicate an increased subsidence in the second half of the twenty-first century. Potential simulated land subsidence extends into urban areas and the eastern side of the valley where future surface-water deliveries may be depleted. 

  4. Wastewater and greywater reuse on irrigation in centralized and decentralized systems--an integrated approach on water quality, energy consumption and CO2 emissions.

    Science.gov (United States)

    Matos, C; Pereira, S; Amorim, E V; Bentes, I; Briga-Sá, A

    2014-09-15

    Wastewater and greywater have different scales of end-uses in irrigation in Portugal. Wastewater is treated in a central wastewater treatment plant and reused in public/private large areas of irrigation, like agriculture, public gardens and golf courses. On the contrary, greywater reuse is generally applied in in situ small scales, treated and used in the same place, generally in the production site. The main aim of this paper is to compare the two types of systems: a wastewater centralized reuse system (WWCRS) and a greywater decentralized reuse system (GWDRS) in terms of water quality, energy consumption and CO2 emissions. In this paper, the main characteristics of both streams are presented and the degree of treatment required in each stream is analyzed. The advantages and disadvantages of its reuse in different scales, in terms of water quality, energy consumption and CO2 emissions are discussed. A methodology to calculate the energy consumptions and CO2 emissions related to wastewater treatment that may be applied in different cases is presented. A hypothetical example of the two systems: one referring to a WWCRS and the other to a GWDRS is presented. The energy consumption and the CO2 emissions are analyzed and compared. The WWCRS needs a higher degree of treatment and so it spends more energy and leads to more CO2 emissions to the environment than the GWDRS that consumed between 11.8 and 37.5% of the energy consumed in the WWCRS considering the same number of inhabitants served.

  5. Plant hydraulics as a central hub integrating plant and ecosystem function: meeting report for 'Emerging Frontiers in Plant Hydraulics' (Washington, DC, May 2015).

    Science.gov (United States)

    Sack, Lawren; Ball, Marilyn C; Brodersen, Craig; Davis, Stephen D; Des Marais, David L; Donovan, Lisa A; Givnish, Thomas J; Hacke, Uwe G; Huxman, Travis; Jansen, Steven; Jacobsen, Anna L; Johnson, Daniel M; Koch, George W; Maurel, Christophe; McCulloh, Katherine A; McDowell, Nate G; McElrone, Andrew; Meinzer, Frederick C; Melcher, Peter J; North, Gretchen; Pellegrini, Matteo; Pockman, William T; Pratt, R Brandon; Sala, Anna; Santiago, Louis S; Savage, Jessica A; Scoffoni, Christine; Sevanto, Sanna; Sperry, John; Tyerman, Stephen D; Way, Danielle; Holbrook, N Michele

    2016-09-01

    Water plays a central role in plant biology and the efficiency of water transport throughout the plant affects both photosynthetic rate and growth, an influence that scales up deterministically to the productivity of terrestrial ecosystems. Moreover, hydraulic traits mediate the ways in which plants interact with their abiotic and biotic environment. At landscape to global scale, plant hydraulic traits are important in describing the function of ecological communities and ecosystems. Plant hydraulics is increasingly recognized as a central hub within a network by which plant biology is connected to palaeobiology, agronomy, climatology, forestry, community and ecosystem ecology and earth-system science. Such grand challenges as anticipating and mitigating the impacts of climate change, and improving the security and sustainability of our food supply rely on our fundamental knowledge of how water behaves in the cells, tissues, organs, bodies and diverse communities of plants. A workshop, 'Emerging Frontiers in Plant Hydraulics' supported by the National Science Foundation, was held in Washington DC, 2015 to promote open discussion of new ideas, controversies regarding measurements and analyses, and especially, the potential for expansion of up-scaled and down-scaled inter-disciplinary research, and the strengthening of connections between plant hydraulic research, allied fields and global modelling efforts.

  6. Scientific integrity

    DEFF Research Database (Denmark)

    Merlo, Domenico Franco; Vahakangas, Kirsi; Knudsen, Lisbeth E.

    2008-01-01

    consent was obtained.Integrity is central to environmental health research searching for causal relations. It requires open communication and trust and any violation (i.e., research misconduct, including fabrication or falsification of data, plagiarism, conflicting interests, etc.) may endanger...

  7. Do Different Neurons Age Differently? Direct Genome-Wide Analysis of Aging in Single Identified Cholinergic Neurons

    OpenAIRE

    Moroz, Leonid L.; Kohn, Andrea B.

    2010-01-01

    Aplysia californica is a powerful experimental system to study the entire scope of genomic and epigenomic regulation at the resolution of single functionally characterized neurons and is an emerging model in the neurobiology of aging. First, we have identified and cloned a number of evolutionarily conserved genes that are age-related, including components of apoptosis and chromatin remodeling. Second, we performed gene expression profiling of different identified cholinergic neurons between y...

  8. Ethanolic Extract of the Seed of Zizyphus jujuba var. spinosa Ameliorates Cognitive Impairment Induced by Cholinergic Blockade in Mice

    OpenAIRE

    Lee, Hyung Eun; Lee, So Young; Kim, Ju Sun; Park, Se Jin; Kim, Jong Min; Lee, Young Woo; Jung, Jun Man; Kim, Dong hyun; Shin, Bum Young; Jang, Dae Sik; Kang, Sam Sik; Ryu, Jong Hoon

    2013-01-01

    In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activit...

  9. Targeting the non-neuronal cholinergic system in macrophages for the management of infectious diseases and cancer: challenge and promise

    Science.gov (United States)

    Reichrath, Sandra; Reichrath, Jörg; Moussa, Amira-Talaat; Meier, Carola; Tschernig, Thomas

    2016-01-01

    Macrophages represent key players of the immune system exerting highly effective defense mechanisms against microbial infections and cancer that include phagocytosis and programmed cell removal. Recent findings highlight the relevance of the non-neuronal cholinergic system for the regulation of macrophage function that opens promising new concepts for the treatment of infectious diseases and cancer. This mini review summarizes our present knowledge on this topic and gives an outlook on future developments.

  10. Developmental Profile of the Aberrant Dopamine D2 Receptor Response in Striatal Cholinergic Interneurons in DYT1 Dystonia

    OpenAIRE

    Giuseppe Sciamanna; Annalisa Tassone; Giuseppina Martella; Georgia Mandolesi; Francesca Puglisi; Dario Cuomo; Grazia Madeo; Giulia Ponterio; David George Standaert; Paola Bonsi; Antonio Pisani

    2011-01-01

    BACKGROUND: DYT1 dystonia, a severe form of genetically determined human dystonia, exhibits reduced penetrance among carriers and begins usually during adolescence. The reasons for such age dependence and variability remain unclear. METHODS AND RESULTS: We characterized the alterations in D2 dopamine receptor (D2R) signalling in striatal cholinergic interneurons at different ages in mice overexpressing human mutant torsinA (hMT). An abnormal excitatory response to the D2R agonist quinpirole w...

  11. Catecholaminergic and cholinergic systems of mouse brain are modulated by LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids.

    Science.gov (United States)

    Fernández-Fernández, Laura; Esteban, Gerard; Giralt, Mercedes; Valente, Tony; Bolea, Irene; Solé, Montse; Sun, Ping; Benítez, Susana; Morelló, José Ramón; Reguant, Jordi; Ramírez, Bartolomé; Hidalgo, Juan; Unzeta, Mercedes

    2015-04-01

    The possible modulatory effect of the functional LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids, on the catecholaminergic and cholinergic neurotransmission, affecting cognition decline during aging has been studied. 129S1/SvlmJ mice were fed for 10, 20, 30 and 40 days with either LMN or control diets. The enzymes involved in catecholaminergic and cholinergic metabolism were determined by both immunohistological and western blot analyses. Noradrenalin, dopamine and other metabolites were quantified by HPLC analysis. Theobromine, present in cocoa, the main LMN diet component, was analysed in parallel using SH-SY5Y and PC12 cell lines. An enhanced modulatory effect on both cholinergic and catecholaminergic transmissions was observed on 20 day fed mice. Similar effect was observed with theobromine, besides its antioxidant capacity inducing SOD-1 and GPx expression. The enhancing effect of the LMN diet and theobromine on the levels of acetylcholine-related enzymes, dopamine and specially noradrenalin confirms the beneficial role of this diet on the "cognitive reserve" and hence a possible reducing effect on cognitive decline underlying aging and Alzheimer's disease. PMID:25756794

  12. Antidepressant-like properties of phosphodiesterase type 5 inhibitors and cholinergic dependency in a genetic rat model of depression.

    Science.gov (United States)

    Liebenberg, Nico; Harvey, Brian H; Brand, Linda; Brink, Christiaan B

    2010-09-01

    We explored the antidepressant-like properties of two phosphodiesterase type 5 (PDE5) inhibitors in a genetic animal model of depression, namely Flinders sensitive line rats. We investigated the dose-dependency of the antidepressant-like action of sildenafil, and its interaction with the cholinergic system and behavioural correlates of monoaminergic neurotransmission, in the forced swim test. Antidepressant-like properties of tadalafil (a structurally distinct PDE5 inhibitor) were also evaluated. Flinders sensitive line rats were treated for 14 days with vehicle, fluoxetine, atropine or PDE5 inhibitors+/-atropine. Immobility, swimming and climbing behaviours were assessed in the forced swim test. In combination with atropine (1 mg/kg), both sildenafil (10, 20 mg/kg) and tadalafil (10 mg/kg) decreased immobility while increasing swimming (serotonergic) and climbing (noradrenergic) behaviours. Interestingly, sildenafil (3 mg/kg) decreased immobility while selectively increasing climbing behaviour in the absence of atropine. These results suggest that the antidepressant-like activity of PDE5 inhibitors involve alterations in monoaminergic neurotransmission, but involve a dependence on inherent cholinergic tone so that the final response is determined by the relative extent of activation of these systems. Furthermore, the behavioural profile of sildenafil alone, and its observed antidepressant-like properties, shows strict dose-dependency, with only higher doses showing an interaction with the cholinergic system.

  13. Involvement of the Nonneuronal Cholinergic System in Bone Remodeling in Rat Midpalatal Suture after Rapid Maxillary Expansion

    Science.gov (United States)

    Guo, Jie; Wang, Lue; Miao, Cong; Ge, Lihua; Tian, Zhenchuan; Wang, Jianhong

    2016-01-01

    Few studies sought to analyze the expression and function of the nonneuronal acetylcholine system in bone remodeling in vivo due to the lack of suitable models. We established a rat maxilla expansion model in which the midline palatine suture of the rat was rapidly expanded under mechanical force application, inducing tissue remodeling and new bone formation, which could be a suitable model to investigate the role of the nonneuronal acetylcholine system in bone remodeling in vivo. During the expansion, the expression pattern changes of the nonneuronal cholinergic system components and the mRNA levels of OPG/RANKL were detected by immunohistochemistry or real-time PCR. The value of the RANKL/OPG ratio significantly increased after 1 day of expansion, indicating dominant bone resorption induced by the mechanical stimulation; however after 3 days of expansion, the value of the RANKL/OPG ratio significantly decreased, suggesting a dominant role of the subsequent bone formation process. Increasing expression of Ach was detected after 3 days of expansion which indicated that ACh might play a role in bone formation. The mRNA expression levels of other components also showed observable changes during the expansion which confirmed the involvement of the nonneuronal cholinergic system in the process of bone remodeling in vivo. Further researches are still needed to figure out the detailed functions of the nonneuronal cholinergic system and its components. PMID:27478838

  14. Pharmacological Mechanisms of Cortical Enhancement Induced by the Repetitive Pairing of Visual/Cholinergic Stimulation.

    Directory of Open Access Journals (Sweden)

    Jun-Il Kang

    Full Text Available Repetitive visual training paired with electrical activation of cholinergic projections to the primary visual cortex (V1 induces long-term enhancement of cortical processing in response to the visual training stimulus. To better determine the receptor subtypes mediating this effect the selective pharmacological blockade of V1 nicotinic (nAChR, M1 and M2 muscarinic (mAChR or GABAergic A (GABAAR receptors was performed during the training session and visual evoked potentials (VEPs were recorded before and after training. The training session consisted of the exposure of awake, adult rats to an orientation-specific 0.12 CPD grating paired with an electrical stimulation of the basal forebrain for a duration of 1 week for 10 minutes per day. Pharmacological agents were infused intracortically during this period. The post-training VEP amplitude was significantly increased compared to the pre-training values for the trained spatial frequency and to adjacent spatial frequencies up to 0.3 CPD, suggesting a long-term increase of V1 sensitivity. This increase was totally blocked by the nAChR antagonist as well as by an M2 mAChR subtype and GABAAR antagonist. Moreover, administration of the M2 mAChR antagonist also significantly decreased the amplitude of the control VEPs, suggesting a suppressive effect on cortical responsiveness. However, the M1 mAChR antagonist blocked the increase of the VEP amplitude only for the high spatial frequency (0.3 CPD, suggesting that M1 role was limited to the spread of the enhancement effect to a higher spatial frequency. More generally, all the drugs used did block the VEP increase at 0.3 CPD. Further, use of each of the aforementioned receptor antagonists blocked training-induced changes in gamma and beta band oscillations. These findings demonstrate that visual training coupled with cholinergic stimulation improved perceptual sensitivity by enhancing cortical responsiveness in V1. This enhancement is mainly mediated by n

  15. Effect of bilobalide B on cholinergic hippocampal neurons exposed to cholesterol and apoliprotein E4

    Institute of Scientific and Technical Information of China (English)

    Xijuan Jiang; Bin Lu; Yingchang Fan

    2008-01-01

    BACKGROUND: Extracts of ginkgo biloba leaves have been reported to improve nerve function and activity in Alzheimer's disease, which is associated with reduced secretion of cholinergic neurotransmitter in hippocampal neurons.OBJECTIVE: To validate the protective effect of bilobalide B against in vitro injury of cholinergic neurons of the hippocampus induced by combined cholesterol and apoE4DESIGN, TIME AND SETTING: This randomized, controlled animal experiment was performed in the Pathology Laboratory, Tianjin University of Traditional Chinese Medicine from July 2003 to July 2006.MATERIALS: Neonatal Wistar rats, 1-day-old, both male and female, and mean body mass of 5g were selected for this study. Cholesterol and apolipoprotein E4 (apoE4) were purchased from Sigma Company (USA), bilobalide B was purchased from Tianjin Zhongyi Pharmaceutical Factory, batch number 20050312.METHODS: Hippocampal neurons were divided into three groups; a normal control group (routinely added media), a model group (exposed to media containing 40mg/L cholesterol and 30mg/L apoE4 for 24 hours) and a bilobalide B group (exposed to media containing 160mg/L bilobalide B for 16 hours, and then with addition of 40mg/L cholesterol and 30mg/L apoE4 for an additional 24 hours).MAIN OUTCOME MEASURES: Levels of acetylcholine (ACh) and activity of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) in hippocampal neurons were determined by microdosage hydroxylamine colorimetry, hydroxylamine colorimetry and radiological chemistry, respectively.RESULTS: The ACh level was significantly lower in the model group than that in the normal control group (P0.05). Activity of ChAT was significantly lower in the model group than in the normal control group (P<0.01), while the activity was significantly higher in the bilobalide B group than in the model group (P<0.05).CONCLUSION: Bilobalide B can enhance the ACh level of hippocampal neurons damaged by combined cholesterol and apoE4, by promoting

  16. Commentary - The Early Days of Central Asian Military Integration: the Kyrgyz National Division of the Red Army in 1927-1928

    Directory of Open Access Journals (Sweden)

    Isabelle Ohayon

    2009-12-01

    Full Text Available This paper is a brief overview of the sociology of a national division of the Red Army in the early days of its formation in Kyrgyzstan, as described in two documents about soldiers of Kyrgyz nationality in 1927 and 1928. At that time the Soviet Army was not seeking to substantially increase its numbers but rather recruiting in line with the intentions of the nationality policy, by integrating ethnic groups and regions that had been ignored by the high command. Kyrgyzstan is a striking exampl...

  17. Effects of melatonin on learning abilities, cholinergic fibers and nitric oxide synthase expression in rat cerebral cortex

    Institute of Scientific and Technical Information of China (English)

    Bin Xu; Junpao Chen; Hailing Zhao

    2006-01-01

    BACKGROUND: Melatonin is a kind of hormones derived from pineal gland. Recent researches demonstrate that melatonin is characterized by anti-oxidation, anti-senility and destroying free radicals. While, effect and pathogenesis of pineal gland on learning ability should be further studied.OBJ ECTIVE: To investigate the effects of pinealectomy on learning abiliy, distribution of cholinesterase and expression of neuronal nitric oxide synthase (nNOS) in cerebral cortex of rats and probe into the effect of melatonin on learning ability, central cholinergic system and nNOS expression.DESIGN: Randomized grouping design and animal study.SETTING: Department of Neurology, the 187 Hospital of Chinese PLA.MATERIALS: A total of 12 male SD rats, of normal learning ability testing with Y-tape maze, of clean grade,weighing 190-210 g, aged 6 weeks, were selected in this study.METHODS: The experiment was carried out in the Department of Neurology, Zhujiang Hospital from July 1997to June 2000. All SD rats were divided into experimental group (n =6,pinealectomy) and control group (n =6, sham operation). Seven days later, rats in both two groups were continuously fed for 33 days. ①Learning ability test: The learning ability of rats was tested by trisection Y-type maze and figured as attempting times. ②Expression of acetylcholinesterase (AchE) was detected by enzyme histochemistry and nNOS was measured by SABC method. ③ Quantitative analysis of AchE fibers: AchE fibers density in unit area (surface density)was surveyed with Leica Diaplan microscope and Leica Quantimet 500+ image analytic apparatus and quantitative parameter was set up for AchE fibers covering density (μm2) per 374 693.656 μm2, moreover, the AchE fibers density was measured in Ⅱ -Ⅳ layers of motor and somatosensory cortex (showing three layers per field of vision at one time), in radiative, lacunaria and molecular layers of CA1, CA2 and CA3 areas, and in lamina multiforms of dentate gyrus. Three tissue slices

  18. Fade of the responses of the isolated, blood-perfused dog atrium to cholinergic interventions.

    Science.gov (United States)

    Furukawa, Y; Martin, P; Levy, M N

    1984-05-01

    In the isolated, blood-perfused, canine right atrium, intramural parasympathetic nerve stimulation and intra-arterial infusions of acetylcholine induced substantial negative chronotropic and inotropic responses. The responses to parasympathetic stimulation reached their maximum values quickly, and then usually faded back toward control levels over the next 1 or 2 min of stimulation. The fade of the responses at high stimulation frequencies (greater than or equal to 30 Hz) was significantly greater than that at lower frequencies. The inotropic responses to acetylcholine infusion (1 microgram/min) faded slightly but significantly, whereas the chronotropic responses did not fade at all. These results suggest that the fade of the cardiac responses to parasympathetic stimulation is mainly ascribable to a progressive reduction in the rate of acetylcholine release from the nerve endings, especially at higher stimulation frequencies. The fade of the inotropic responses was more pronounced and had a longer time course than that of the chronotropic responses. Furthermore, the fade of the inotropic responses diminished significantly as the response magnitude was augmented by an increase in stimulation voltage. Conversely, the fade of chronotropic responses was not significantly affected by this intervention. These differences in the inotropic and chronotropic responses to neural stimulation, and the occurrence of a slight fade of the inotropic response to acetylcholine infusion, suggest that in addition to the predominant prejunctional mechanism, a postjunctional phenomenon may also be partly responsible for the fade of the inotropic response to cholinergic interventions.

  19. Cuneiform neurons activated during cholinergically induced active sleep in the cat.

    Science.gov (United States)

    Pose, I; Sampogna, S; Chase, M H; Morales, F R

    2000-05-01

    In the present study, we report that the cuneiform (Cun) nucleus, a brainstem structure that before now has not been implicated in sleep processes, exhibits a large number of neurons that express c-fos during carbachol-induced active sleep (AS-carbachol). Compared with control (awake) cats, during AS-carbachol, there was a 671% increase in the number of neurons that expressed c-fos in this structure. Within the Cun nucleus, three immunocytochemically distinct populations of neurons were observed. One group consisted of GABAergic neurons, which predominantly did not express c-fos during AS-carbachol. Two other different populations expressed c-fos during this state. One of the Fos-positive (Fos(+)) populations consisted of a distinct group of nitric oxide synthase (NOS)-NADPH-diaphorase (NADPH-d)-containing neurons; the neurotransmitter of the other Fos(+) population remains unknown. The Cun nucleus did not contain cholinergic, catecholaminergic, serotonergic, or glycinergic neurons. On the basis of neuronal activation during AS-carbachol, as indicated by c-fos expression, we suggest that the Cun nucleus is involved, in an as yet unknown manner, in the physiological expression of active sleep. The finding of a population of NOS-NADPH-d containing neurons, which were activated during AS-carbachol, suggests that nitrergic modulation of their target cell groups is likely to play a role in active sleep-related physiological processes. PMID:10777795

  20. Network burst dynamics under heterogeneous cholinergic modulation of neural firing properties and heterogeneous synaptic connectivity.

    Science.gov (United States)

    Knudstrup, Scott; Zochowski, Michal; Booth, Victoria

    2016-05-01

    The characteristics of neural network activity depend on intrinsic neural properties and synaptic connectivity in the network. In brain networks, both of these properties are critically affected by the type and levels of neuromodulators present. The expression of many of the most powerful neuromodulators, including acetylcholine (ACh), varies tonically and phasically with behavioural state, leading to dynamic, heterogeneous changes in intrinsic neural properties and synaptic connectivity properties. Namely, ACh significantly alters neural firing properties as measured by the phase response curve in a manner that has been shown to alter the propensity for network synchronization. The aim of this simulation study was to build an understanding of how heterogeneity in cholinergic modulation of neural firing properties and heterogeneity in synaptic connectivity affect the initiation and maintenance of synchronous network bursting in excitatory networks. We show that cells that display different levels of ACh modulation have differential roles in generating network activity: weakly modulated cells are necessary for burst initiation and provide synchronizing drive to the rest of the network, whereas strongly modulated cells provide the overall activity level necessary to sustain burst firing. By applying several quantitative measures of network activity, we further show that the existence of network bursting and its characteristics, such as burst duration and intraburst synchrony, are dependent on the fraction of cell types providing the synaptic connections in the network. These results suggest mechanisms underlying ACh modulation of brain oscillations and the modulation of seizure activity during sleep states. PMID:26869313

  1. Different correlation patterns of cholinergic and GABAergic interneurons with striatal projection neurons

    Directory of Open Access Journals (Sweden)

    Avital eAdler

    2013-09-01

    Full Text Available The striatum is populated by a single projection neuron group, the medium spiny neurons (MSNs, and several groups of interneurons. Two of the electrophysiologically well-characterized striatal interneuron groups are the tonically active neurons (TANs, which are presumably cholinergic interneurons, and the fast spiking interneurons (FSIs, presumably parvalbumin (PV expressing GABAergic interneurons. To better understand striatal processing it is thus crucial to define the functional relationship between MSNs and these interneurons in the awake and behaving animal. We used multiple electrodes and standard physiological methods to simultaneously record MSN spiking activity and the activity of TANs or FSIs from monkeys engaged in a classical conditioning paradigm. All three cell populations were highly responsive to the behavioral task. However, they displayed different average response profiles and a different degree of response synchronization (signal correlation. TANs displayed the most transient and synchronized response, MSNs the most diverse and sustained response and FSIs were in between on both parameters. We did not find evidence for direct monosynaptic connectivity between the MSNs and either the TANs or the FSIs. However, while the cross correlation histograms of TAN to MSN pairs were flat, those of FSI to MSN displayed positive asymmetrical broad peaks. The FSI-MSN correlogram profile implies that the spikes of MSNs follow those of FSIs and both are driven by a common, most likely cortical, input. Thus, the two populations of striatal interneurons are probably driven by different afferents and play complementary functional roles in the physiology of the striatal microcircuit.

  2. Amphetamine sensitization and amygdala kindling: pharmacological evaluation of catecholaminergic and cholinergic mechanisms.

    Science.gov (United States)

    Kirkby, R D; Kokkinidis, L

    1991-03-01

    Chronic pharmacological experiments were conducted to evaluate the relationship between sensitization induced by repeated administration of amphetamine (AMPH) and electrical stimulation of the amygdala. While AMPH withdrawal did not influence the kindling process, AMPH administered during the kindling procedure increased the rate at which seizures evolved, and under these conditions withdrawal from chronic AMPH further facilitated the propensity to kindle. Haloperidol (HAL) treatment failed to block the stimulant-induced increase in kindling acquisition indicating that changes in dopamine (DA) are not necessary for the AMPH/kindling synergism to develop. Scopolamine dose-dependently retarded kindling evolution irrespective of prior AMPH pretreatment also ruling out a cholinergic mechanism in the kindling sensitization. Subsequent experiments assessed the interactive effects of AMPH and desipramine (DMI) on the kindling process. Animals chronically exposed to AMPH and switched to DMI treatment during the kindling procedure kindled faster than control subjects. In addition, withdrawal from DMI preexposure advanced the AMPH-induced increase in kindling rate. These results were discussed in terms of the role of norepinephrine-mediated inhibition of the kindling process, and were related to drug-elicited alterations in beta-adrenergic receptor functioning. Taken together, these findings implicate the amygdala as an important structure in the development of non-DA forms of AMPH sensitization.

  3. Deformation of attractor landscape via cholinergic presynaptic modulations: a computational study using a phase neuron model.

    Directory of Open Access Journals (Sweden)

    Takashi Kanamaru

    Full Text Available Corticopetal acetylcholine (ACh is released transiently from the nucleus basalis of Meynert (NBM into the cortical layers and is associated with top-down attention. Recent experimental data suggest that this release of ACh disinhibits layer 2/3 pyramidal neurons (PYRs via muscarinic presynaptic effects on inhibitory synapses. Together with other possible presynaptic cholinergic effects on excitatory synapses, this may result in dynamic and temporal modifications of synapses associated with top-down attention. However, the system-level consequences and cognitive relevance of such disinhibitions are poorly understood. Herein, we propose a theoretical possibility that such transient modifications of connectivity associated with ACh release, in addition to top-down glutamatergic input, may provide a neural mechanism for the temporal reactivation of attractors as neural correlates of memories. With baseline levels of ACh, the brain returns to quasi-attractor states, exhibiting transitive dynamics between several intrinsic internal states. This suggests that top-down attention may cause the attention-induced deformations between two types of attractor landscapes: the quasi-attractor landscape (Q-landscape, present under low-ACh, non-attentional conditions and the attractor landscape (A-landscape, present under high-ACh, top-down attentional conditions. We present a conceptual computational model based on experimental knowledge of the structure of PYRs and interneurons (INs in cortical layers 1 and 2/3 and discuss the possible physiological implications of our results.

  4. Ligands for SPECT and PET imaging of muscarinic-cholinergic receptors of the heart and brain

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, F.F. Jr.; McPherson, D.W.; Luo, H. [and others

    1995-06-01

    Interest in the potential use of cerebral SPECT and PET imaging for determination of the density and activity of muscarinic-cholinergic receptors (mAChR) has been stimulated by the changes in these receptors which occur in many neurological diseases. In addition, the important involvement of mAChR in modulating negative inotropic cardiac activity suggests that such receptor ligands may have important applications in evaluation of changes which may occur in cardiac disease. In this paper, the properties of several key muscarinic receptor ligands being developed or which have been used for clinical SPECT and PET are discussed. In addition, the ORNL development of the new iodinated IQNP ligand based on QNB and the results of in vivo biodistribution studies in rats, in vitro competitive binding studies and ex vivo autoradiographic experiments are described. The use of radioiodinated IQNP may offer several advantages in comparison to IQNB because of its easy and high yield preparation and high brain uptake and the potential usefulness of the {open_quotes}partial{close_quotes} subtype selective IONP isomers. We also describe the development of new IQNP-type analogues which offer the opportunity for radiolabeling with positron-emitting radioisotopes (carbon-11, fluorine-18 and bromine-76) for potential use with PET.

  5. Adrenergic and cholinergic responses in the uteroplacental vascular bed of the guinea pig

    International Nuclear Information System (INIS)

    The effects on uterine and maternal placental circulation of adrenergic and cholinergic drugs, injected selectively in the ovarian and uterine arteries of guinea pigs, were analysed by serial angiography. Noradrenaline, 0.5 nmol/kg, was found to cause a reduction in both ovarian and uterine blood flow, associated with arterial vasoconstriction and impairment of the placental circulation. This response could be prevented by α-adrenergic blockade with 25 nmol/kg phenoxybenzamine. At injection into the ovarian artery, phenoxybenzamine alone increased ovarian blood flow and elicited arterial vasodilatation. At injection into the uterine artery the response was more variable, but vasodilatation was observed in four animals of six. Acetylcholine, 0.5 to 5.0 nmol/kg, evoked an increase in both ovarian and uterine blood flow and arterial vasodilatation. When the dose was increased to 50 nmol/kg, dilatation of the extrinsic uterine arteries was maintained, but the placental circulation was reduced due to concomitant contraction of the myometrium. All the effects of acetylcholine could be blocked by prior administration of 10 nmol/kg atropine. This dose of atropine did not affect uterine or placental circulation when given alone. (Auth.)

  6. Cholinergic pairing with visual activation results in long-term enhancement of visual evoked potentials.

    Directory of Open Access Journals (Sweden)

    Jun Il Kang

    Full Text Available Acetylcholine (ACh contributes to learning processes by modulating cortical plasticity in terms of intensity of neuronal activity and selectivity properties of cortical neurons. However, it is not known if ACh induces long term effects within the primary visual cortex (V1 that could sustain visual learning mechanisms. In the present study we analyzed visual evoked potentials (VEPs in V1 of rats during a 4-8 h period after coupling visual stimulation to an intracortical injection of ACh analog carbachol or stimulation of basal forebrain. To clarify the action of ACh on VEP activity in V1, we individually pre-injected muscarinic (scopolamine, nicotinic (mecamylamine, alpha7 (methyllycaconitine, and NMDA (CPP receptor antagonists before carbachol infusion. Stimulation of the cholinergic system paired with visual stimulation significantly increased VEP amplitude (56% during a 6 h period. Pre-treatment with scopolamine, mecamylamine and CPP completely abolished this long-term enhancement, while alpha7 inhibition induced an instant increase of VEP amplitude. This suggests a role of ACh in facilitating visual stimuli responsiveness through mechanisms comparable to LTP which involve nicotinic and muscarinic receptors with an interaction of NMDA transmission in the visual cortex.

  7. Network burst dynamics under heterogeneous cholinergic modulation of neural firing properties and heterogeneous synaptic connectivity

    Science.gov (United States)

    Knudstrup, Scott; Zochowski, Michal; Booth, Victoria

    2016-01-01

    The characteristics of neural network activity depend on intrinsic neural properties and synaptic connectivity in the network. In brain networks, both of these properties are critically affected by the type and levels of neuromodulators present. The expression of many of the most powerful neuromodulators, including acetylcholine (ACh), varies tonically and phasically with behavioural state, leading to dynamic, heterogeneous changes in intrinsic neural properties and synaptic connectivity properties. Namely, ACh significantly alters neural firing properties as measured by the phase response curve in a manner that has been shown to alter the propensity for network synchronization. The aim of this simulation study was to build an understanding of how heterogeneity in cholinergic modulation of neural firing properties and heterogeneity in synaptic connectivity affect the initiation and maintenance of synchronous network bursting in excitatory networks. We show that cells that display different levels of ACh modulation have differential roles in generating network activity: weakly modulated cells are necessary for burst initiation and provide synchronizing drive to the rest of the network, whereas strongly modulated cells provide the overall activity level necessary to sustain burst firing. By applying several quantitative measures of network activity, we further show that the existence of network bursting and its characteristics, such as burst duration and intraburst synchrony, are dependent on the fraction of cell types providing the synaptic connections in the network. These results suggest mechanisms underlying ACh modulation of brain oscillations and the modulation of seizure activity during sleep states. PMID:26869313

  8. Noradrenergic and cholinergic modulation of late ERP responses to deviant stimuli.

    Science.gov (United States)

    Brown, Stephen B R E; van der Wee, Nic J A; van Noorden, Martijn S; Giltay, Erik J; Nieuwenhuis, Sander

    2015-12-01

    Researchers have proposed several hypotheses about the neuromodulator systems involved in generating P3 components of the ERP. To test some of these hypotheses, we conducted a randomized placebo-controlled crossover study in which we investigated how the late positive ERP response to deviant stimuli is modulated by (a) clonidine, an α2 agonist that attenuates baseline noradrenergic activity; and (b) scopolamine, a muscarinic antagonist of acetylcholine receptors. We collected EEG data from 18 healthy volunteers during the performance of an auditory oddball task with several active and passive task conditions. We then used temporospatial principal component analysis (PCA) to decompose the ERP waveforms. The PCA revealed two distinct late positive ERP components: the classic parietal P300 and the frontal novelty P3. Statistical analysis of the temporospatial factor scores indicated that in most conditions the amplitude of the classic P300 was increased by clonidine and scopolamine. In contrast, the amplitude of the novelty P3 was decreased by both drugs. The similar pattern of results for clonidine and scopolamine probably reflects the strong interactions between the noradrenergic and cholinergic systems. The results, in combination with previous pharmacological studies, suggest a critical role for both neuromodulator systems in the generation of the P300 and the novelty P3.

  9. Behavioral deficits and cholinergic pathway abnormalities in male Sanfilippo B mice.

    Science.gov (United States)

    Kan, Shih-Hsin; Le, Steven Q; Bui, Quang D; Benedict, Braeden; Cushman, Jesse; Sands, Mark S; Dickson, Patricia I

    2016-10-01

    Sanfilippo B syndrome is a progressive neurological disorder caused by inability to catabolize heparan sulfate glycosaminoglycans. We studied neurobehavior in male Sanfilippo B mice and heterozygous littermate controls from 16 to 20 weeks of age. Affected mice showed reduced anxiety, with a decrease in the number of stretch-attend postures during the elevated plus maze (p=0.001) and an increased tendency to linger in the center of an open field (p=0.032). Water maze testing showed impaired spatial learning, with reduced preference for the target quadrant (p=0.01). In radial arm maze testing, affected mice failed to achieve above-chance performance in a win-shift working memory task (t-test relative to 50% chance: p=0.289), relative to controls (p=0.037). We found a 12.4% reduction in mean acetylcholinesterase activity (padult-onset dementias, including Alzheimer disease. Our results suggest that male Sanfilippo B mice display neurobehavioral deficits at a relatively early age, and that as in adult dementias, they may display deficits in cholinergic pathways. PMID:27340089

  10. Atrophy and structural covariance of the cholinergic basal forebrain in primary progressive aphasia.

    Science.gov (United States)

    Teipel, Stefan; Raiser, Theresa; Riedl, Lina; Riederer, Isabelle; Schroeter, Matthias L; Bisenius, Sandrine; Schneider, Anja; Kornhuber, Johannes; Fliessbach, Klaus; Spottke, Annika; Grothe, Michel J; Prudlo, Johannes; Kassubek, Jan; Ludolph, Albert; Landwehrmeyer, Bernhard; Straub, Sarah; Otto, Markus; Danek, Adrian

    2016-10-01

    Primary progressive aphasia (PPA) is characterized by profound destruction of cortical language areas. Anatomical studies suggest an involvement of cholinergic basal forebrain (BF) in PPA syndromes, particularly in the area of the nucleus subputaminalis (NSP). Here we aimed to determine the pattern of atrophy and structural covariance as a proxy of structural connectivity of BF nuclei in PPA variants. We studied 62 prospectively recruited cases with the clinical diagnosis of PPA and 31 healthy older control participants from the cohort study of the German consortium for frontotemporal lobar degeneration (FTLD). We determined cortical and BF atrophy based on high-resolution magnetic resonance imaging (MRI) scans. Patterns of structural covariance of BF with cortical regions were determined using voxel-based partial least square analysis. We found significant atrophy of total BF and BF subregions in PPA patients compared with controls [F(1, 82) = 20.2, p covariance analysis in healthy controls revealed associations of the BF nuclei, particularly the NSP, with left hemispheric predominant prefrontal, lateral temporal, and parietal cortical areas, including Broca's speech area (p covariance of the BF nuclei mostly with right but not with left hemispheric cortical areas (p covariance of the BF with left hemispheric cortical areas in healthy aging towards right hemispheric cortical areas in PPA, possibly reflecting a consequence of the profound and early destruction of cortical language areas in PPA.

  11. Network burst dynamics under heterogeneous cholinergic modulation of neural firing properties and heterogeneous synaptic connectivity.

    Science.gov (United States)

    Knudstrup, Scott; Zochowski, Michal; Booth, Victoria

    2016-05-01

    The characteristics of neural network activity depend on intrinsic neural properties and synaptic connectivity in the network. In brain networks, both of these properties are critically affected by the type and levels of neuromodulators present. The expression of many of the most powerful neuromodulators, including acetylcholine (ACh), varies tonically and phasically with behavioural state, leading to dynamic, heterogeneous changes in intrinsic neural properties and synaptic connectivity properties. Namely, ACh significantly alters neural firing properties as measured by the phase response curve in a manner that has been shown to alter the propensity for network synchronization. The aim of this simulation study was to build an understanding of how heterogeneity in cholinergic modulation of neural firing properties and heterogeneity in synaptic connectivity affect the initiation and maintenance of synchronous network bursting in excitatory networks. We show that cells that display different levels of ACh modulation have differential roles in generating network activity: weakly modulated cells are necessary for burst initiation and provide synchronizing drive to the rest of the network, whereas strongly modulated cells provide the overall activity level necessary to sustain burst firing. By applying several quantitative measures of network activity, we further show that the existence of network bursting and its characteristics, such as burst duration and intraburst synchrony, are dependent on the fraction of cell types providing the synaptic connections in the network. These results suggest mechanisms underlying ACh modulation of brain oscillations and the modulation of seizure activity during sleep states.

  12. Protein kinase C mediates cholinergically regulated protein phosphorylation in a Cl(-)-secreting epithelium.

    Science.gov (United States)

    Cohn, J A

    1990-02-01

    T84 cell monolayers were used to study the cholinergic regulation of protein phosphorylation in epithelial cells. When T84 cell monolayers are labeled with 32Pi and stimulated with carbachol, six proteins exhibit altered phosphorylation. The most prominent response is a fivefold increase in labeling of p83, an acidic protein of Mr 83,000. Increasing labeling of p83 parallels stimulated secretion with respect to the onset of agonist action, agonist potency, and antagonism by atropine. However, the p83 and secretory responses differ in that the p83 response is more sustained. When T84 cell fractions are incubated with [gamma-32P]ATP, Ca2(+)-phospholipid stimulates p83 labeling. Phosphorylation of p83 also occurs when a T84 cell extract is incubated with purified protein kinase C and when intact cells are exposed to phorbol myristate acetate. p83 does not become phosphorylated in cell fractions incubated with adenosine 3',5'-cyclic monophosphate (cAMP) or in monolayers stimulated with agonists acting via cAMP. Thus carbachol stimulates the phosphorylation of an endogenous substrate for protein kinase C in T84 cells. The duration of this phosphorylation response suggests that protein kinase C may mediate a sustained response to carbachol, possibly acting to limit the duration of stimulated secretion.

  13. UNILATERAL MYDRIASIS WITH CHOLINERGIC SUPER SENSITIVITY: A DIAGNOSTIC DILEMMA - A CASE SERIES REPORT

    Directory of Open Access Journals (Sweden)

    Sandhya

    2014-05-01

    Full Text Available Pupillary abnormalities are a common feature of general ophthalmic practice. It often causes confusion as they can be manifestations of local and/ or systemic diseases. These diseases may range from vision threatening to life endangering to innocuous ones. A keen observational and clinical skill can help the ophthalmologist in diagnosis & timely referral when necessary. We report 3 cases of acquired mydriasis, with cholinergic supersensitivity. The short history poses a diagnostic dilemma as to whether it is Adie’s Tonic pupil or a harbinger of a serious neurological problem. 2 of the patients with mydriasis were younger, 32 & 35 years of age, presenting with recent onset of blurring of Vision for distance and difficulty in reading. The 3rd patient was a 45 year old presbyope who presented with sudden drop in near vision in one eye. Our cases raise several important question regarding so-called “benign pupillary dilation of the young” and its relationship with Adie‘s tonic pupil. Demonstration of probable transient parasympathetic dysfunction suggests that pharmacologic testing with dilute pilocarpine should be considered in patients reporting with near vision problems with isolated unilateral recent onset mydriasis which is probably intermittent. Thorough history and basic clinical neurological examination are mandatory. The importance of timely referral to neurologist must be borne in mind always in such cases.

  14. Integrating field measurements, a geomorphological map and stochastic modelling to estimate the spatially distributed rockfall sediment budget of the Upper Kaunertal, Austrian Central Alps

    Science.gov (United States)

    Heckmann, Tobias; Hilger, Ludwig; Vehling, Lucas; Becht, Michael

    2016-05-01

    The estimation of catchment-scale rockfall rates relies on the regionalisation of local measurements. Here, we propose a new framework for such a regionalisation by the example of a case study in the Upper Kaunertal, Austrian Central Alps (62.5 km2). Measurements of rockfall deposition during 12 months onto six collector nets within the study area were combined with published mean annual rates from the literature, and a probability density function was fitted to these data. A numerical model involving a random walk routing scheme and a one-parameter friction model was used to simulate rockfall trajectories, starting from potential rockfall source areas that were delineated from a digital elevation model. Rockfall rates sampled from the fitted probability density function were assigned to these trajectories in order to model the spatial distribution and to estimate the amount of rockfall deposition. By recording all trajectories as edges of a network of raster cells, and by aggregating the latter to landforms (or landform types) as delineated in a geomorphological map of the study area, rockfall sediment flux from sources to different landforms could be quantified. Specifically, the geomorphic coupling of rockfall sources to storage landforms and the glacial and fluvial sediment cascade was investigated using this network model. The total rockfall contribution to the sediment budget of the Upper Kaunertal is estimated at c. 8000 Mg yr- 1, 16.5% of which is delivered to the glaciers, and hence to the proglacial zone. The network approach is favourable, for example because multiple scenarios (involving different probability density functions) can be calculated on the basis of the same set of trajectories, and because deposits can be back-linked to their respective sources. While the methodological framework constitutes the main aim of our paper, we also discuss how the estimation of the budget can be improved on the basis of spatially distributed production rates.

  15. An Integration of Geophysical Methods for the Determination of Subsurface Structure of the Intra-Mountain Plains: The CASES of Rieti and Leonessa (CENTRAL APENNINES, ITALY)

    Science.gov (United States)

    Skrame, K.; Di Filippo, M.; Di Nezza, M.

    2014-12-01

    This work, carried out with an integrated methodological approach, describes the acquisition of gravity data and their integration with different geophysical techniques, in order to map and model the thickness of unconsolidated deposits and determine the bedrock configuration of two different intra-mountain plains: Leonessa plain (hereafter LP) and Rieti plain (hereafter RP). The LP and the RP, the test areas of this study, are typical intra-mountain depressions of Center Apennines, related to the Plio-Quaternary extensional tectonic. Both basins are characterized by thick Quaternary fluvial-lacustrine deposits (gravel, sand and clay) overlaying the Meso-Cenozoic pelagic basin deposits. On the LP, the study involved an area of 62 km2 occupied by 333 gravity stations. Instead, on the RP, the study area, of 35 km2, were occupied by 170 gravity stations. The gravity data resulted from the network adjustment were used to calculate the Bouguer anomaly map. Subtracting the regional field from the Bouguer anomaly produced the residual anomaly map. In order to determine the distribution of the sedimentary infill, a 2D gravity modeling was developed in the region, including five profiles in the case study of LP and six profiles in the case study of RP. A realistic density of the unconsolidated Quaternary deposits (1.75-2,00 g/cm3 in the case of LP and 2,15 g/cm3 in the case of RP), a density of 2.50 g/cm3 for the Travertine and a density of 2.60 g/cm3 for the Meso-Cenozoic pelagic basin deposits were used to constrain the 2D gravimetric models. The models match quite well with the information determined from a collection of existing well logs and geophysical data obtained by the ambient noise, MASW and Downhole measurements. Finally, referring to these models, we were able to evaluate the thickness of the Quaternary sedimentary infilling and to define the 3D bedrock configuration of the basins. These 3D models represent a useful starting point for future activities such as

  16. Identification and functional expression of a family of nicotinic acetylcholine receptor subunits in the central nervous system of the mollusc Lymnaea stagnalis.

    Science.gov (United States)

    van Nierop, Pim; Bertrand, Sonia; Munno, David W; Gouwenberg, Yvonne; van Minnen, Jan; Spafford, J David; Syed, Naweed I; Bertrand, Daniel; Smit, August B

    2006-01-20

    We described a family of nicotinic acetylcholine receptor (nAChR) subunits underlying cholinergic transmission in the central nervous system (CNS) of the mollusc Lymnaea stagnalis. By using degenerate PCR cloning, we identified 12 subunits that display a high sequence similarity to nAChR subunits, of which 10 are of the alpha-type, 1 is of the beta-type, and 1 was not classified because of insufficient sequence information. Heterologous expression of identified subunits confirms their capacity to form functional receptors responding to acetylcholine. The alpha-type subunits can be divided into groups that appear to underlie cation-conducting (excitatory) and anion-conducting (inhibitory) channels involved in synaptic cholinergic transmission. The expression of the Lymnaea nAChR subunits, assessed by real time quantitative PCR and in situ hybridization, indicates that it is localized to neurons and widespread in the CNS, with the number and localization of expressing neurons differing considerably between subunit types. At least 10% of the CNS neurons showed detectable nAChR subunit expression. In addition, cholinergic neurons, as indicated by the expression of the vesicular ACh transporter, comprise approximately 10% of the neurons in all ganglia. Together, our data suggested a prominent role for fast cholinergic transmission in the Lymnaea CNS by using a number of neuronal nAChR subtypes comparable with vertebrate species but with a functional complexity that may be much higher.

  17. Integrated plant safety assessment: systematic evaluation program. Oyster Creek nuclear generating station. GPU Nuclear Corporation and Jersey Central Power and Light Company. Docket No. 50-219

    International Nuclear Information System (INIS)

    The Systematic Evaluation Program was initiated in February 1978 by the US Nuclear Regulatory Commission to review the designs of older operating nuclear reactor plants to reconfirm and document their safety. The review provides (1) an assessment of how these plants compare with current licensing safety requirements relating to selected issues, (2) a basis for deciding on how these differences should be resolved in an integrated plant review, and (3) a documented evaluation of plant safety. This report documents the review of the Oyster Creek Nuclear Generating Station (located in Ocean County, New Jersey), one of ten plants reviewed under Phase II of this program, and indicates how 137 topics selected for review under Phase I of the program were addressed. Equipment and procedural changes have been identified as a result of the review. It is expected that this report will be one of the bases in considering the issuance of a full-term operating license in place of the existing provisional operating license

  18. Prevalence of haemoparasitic infections in dairy cattle (Friesian breeds at nagari integrated dairy farms, Gauta-Nike village, Keffi local government area, Nasarawa state, north central of Nigeria

    Directory of Open Access Journals (Sweden)

    S.M. Abdullahi

    2014-02-01

    Full Text Available The of prevalence ofhaemoparasites of cattle located in Nagari Integrated Farms, Gauta-NikeVillage, Keffi Local Government Area, Nasarawa State, Nigeria was conducted inOctober 2012 where 50 Friesian cattle (male and females are kept on intensivesystem of management were randomly selected. Blood samples were collected in ananticoagulant sample bottle and submitted to the Parasitology Laboratory ofFaculty of Veterinary Medicine, Ahmadu Bello University Zaria, Kaduna state ofNigeria for parasitological examination. Giemsa stained thin blood smears wereexamined for hemoparasites and Hematocrit Centrifuge Technique (HCT was usedto determine the presence of motile parasites. An overall prevalence of 90%(82% female and 8% male was recorded for all samples examined, 21 (42% wereinfected with Anaplasma marginale, Theileria mutans shows 20 (40% prevalenceand 4 (8% were infected by Babesia bigemina. Mixed infection between Anaplasmamarginale and Babesia bigemina revealed 2 (4% while Anaplasma marginale andTheileria mutans was 7 (14%. There was a significant difference (P > 0.05in infections caused by Anaplasma marginale, Babesia bigemina and Theileriamutans (Table 1 and also between sexes(Table 3,  but there was no significant difference  (P<0.05 between any of the mixedinfections observed (Table 2. The result of this study shows thesehemoparasites are endemic in the cattle under study which may result in seriousdisease conditions when such animals are subjected to stressful condition.

  19. Integrated water resources management in central Asia: nutrient and heavy metal emissions and their relevance for the Kharaa River Basin, Mongolia.

    Science.gov (United States)

    Hofmann, J; Venohr, M; Behrendt, H; Opitz, D

    2010-01-01

    Within the framework of Integrated Water Resources Management (IWRM) the nutrient and heavy metal levels within the Kharaa river basin were investigated. By the application of the MONERIS model, which quantifies nutrient emissions into river basins, various point and diffuse pathways, as well as nutrient load in rivers, could be analysed. Despite seasonal variations and inputs of point sources (e.g. Wastewater Treatment Plant Darkhan) the nutrient concentrations in most of the subbasins are on a moderate level. This shows evidence for a nutrient limited ecosystem as well as dilution effects. However, in the middle and lower reaches heavy metal concentrations of arsenic and mercury, which are linked to mining activities in many cases, are a point of concern. Thus measures are necessary to protect the valuable chemical and ecological status of the Kharaa River and its tributaries. As a result of the growing economic pressure Mongolia will enhance the agricultural production by irrigation. Until 2015 about 60% of the agricultural land shall be irrigated. In addition the gold mining activities shall increase by 20% a year. Both sectors have a high demand for water quantity and quality. The model MONERIS allows the assessment of measures which are inevitable to protect the water quality under shrinking water availability. PMID:20651440

  20. Integrated water resources management in central Asia: nutrient and heavy metal emissions and their relevance for the Kharaa River Basin, Mongolia.

    Science.gov (United States)

    Hofmann, J; Venohr, M; Behrendt, H; Opitz, D

    2010-01-01

    Within the framework of Integrated Water Resources Management (IWRM) the nutrient and heavy metal levels within the Kharaa river basin were investigated. By the application of the MONERIS model, which quantifies nutrient emissions into river basins, various point and diffuse pathways, as well as nutrient load in rivers, could be analysed. Despite seasonal variations and inputs of point sources (e.g. Wastewater Treatment Plant Darkhan) the nutrient concentrations in most of the subbasins are on a moderate level. This shows evidence for a nutrient limited ecosystem as well as dilution effects. However, in the middle and lower reaches heavy metal concentrations of arsenic and mercury, which are linked to mining activities in many cases, are a point of concern. Thus measures are necessary to protect the valuable chemical and ecological status of the Kharaa River and its tributaries. As a result of the growing economic pressure Mongolia will enhance the agricultural production by irrigation. Until 2015 about 60% of the agricultural land shall be irrigated. In addition the gold mining activities shall increase by 20% a year. Both sectors have a high demand for water quantity and quality. The model MONERIS allows the assessment of measures which are inevitable to protect the water quality under shrinking water availability.

  1. Towards an integrated assessment of the impacts of forest residue mulching following wildfire in eucalypt plantations in north-central Portugal

    Science.gov (United States)

    Keizer, Jan Jacob; Abrantes, Nelson; Bastos, Ana; Brandsma, Micha; Campos, Isabel; Faria, Silvia; Malvar, Maruxa; Martins, Martinho; João Oliveira, Maria; Pimpão, Gabriel; Prats, Sergio; Puga, João; Ribeiro, Cristina; Rocha, João; Santos, Liliana; Serpa, Dalila; Silva, Flávio; Silva, Tiago; Valente, Sandra; Vieira, Diana

    2016-04-01

    In the framework of the EU-FP7 project RECARE (www.recare-project.eu) and, in particular, its WP6, the University of Aveiro partner has recently started testing two measures against the soil threat of post-fire erosion by water in an area in north-central Portugal, close to Coimbra that burnt during the summer of 2015. These measures - mulching with forest slash residues and contour ploughing - had been selected by the local and external stakeholders involved in the project, through two subsequent stakeholder workshops. While contour ploughing has still not taken place, the mulching was already carried out, using residues from eucalypt plantations as the burnt areas was dominated by eucalypt plantations, and applying them in a homogeneous fashion at two contrasting application rates, i.e. a "standard" rate of approximately 10 Mg ha-1 and a "reduced" rate of about 3 Mg ha-1. The standard rate was selected for having proved effective in reducing post-fire runoff and erosion in previous field studies in the region (Prats et al., 2012, 2014, 2015a), while the reduced rate had been found to be nearly as effective as the standard rate in a recent study in the hydraulic laboratory of the University of Coimbra (Prats et al., 2015b). Unlike the referred prior studies, however, the present study will also assess the impacts of mulching on two other soil threats - i.e. decline in soil organic matter and in soil biodiversity - and, ultimately, will compare the two measures in terms of their consequences for soil-based ecosystem services, using the framework being developed by RECARE (Schwilch et al. in Stolte et al., 2016). The proposed presentation will show the first results on the effects of the two mulch application rates on post-fire runoff as well as the associated losses of sediments, organic matter/C and nutrients (N, P), and on selected indicators of soil biological activity and diversity. Prats et al., 2015a (in press). LD&D (doi: 10.1002/ldr.2422) Prats et al., 2015

  2. Integrative genomic analyses identify LIN28 and OLIG2 as markers of survival and metastatic potential in childhood central nervous system primitive neuro-ectodermal brain tumours

    Science.gov (United States)

    Picard, Daniel; Miller, Suzanne; Hawkins, Cynthia E; Bouffet, Eric; Rogers, Hazel A; Chan, Tiffany SY; Kim, Seung-Ki; Ra, Young-Shin; Fangusaro, Jason; Korshunov, Andrey; Toledano, Helen; Nakamura, Hideo; Hayden, James T; Chan, Jennifer; Lafay-Cousin, Lucie; Hu, Ping X; Fan, Xing; Muraszko, Karin M; Pomeroy, Scott L; Lau, Ching C; Ng, Ho-Keung; Jones, Chris; Meter, Timothy Van; Clifford, Steven C; Eberhart, Charles; Gajjar, Amar; Pfister, Stefan M; Grundy, Richard G; Huang, Annie

    2013-01-01

    Background Childhood Central Nervous System Primitive Neuro-Ectodermal brain Tumours (CNS-PNETs) are highly aggressive brain tumours for which molecular features and best therapeutic strategy remains unknown. We interrogated a large cohort of these rare tumours in order to identify molecular markers that will enhance clinical management of CNS-PNET. Methods Transcriptional and copy number profiles from primary hemispheric CNS-PNETs were examined using clustering, gene and pathways enrichment analyses to discover tumour sub-groups and group-specific molecular markers. Immuno-histochemical and/or gene expression analyses were used to validate and examine the clinical significance of novel sub-group markers in 123 primary CNS-PNETs. Findings Three molecular sub-groups of CNS-PNETs distinguished by primitive neural (Group 1), oligo-neural (Group 2) and mesenchymal lineage (Group 3) gene expression signature were identified. Tumour sub-groups exhibited differential expression of cell lineage markers, LIN28 and OLIG2, and correlated with distinct demographics, survival and metastatic incidence. Group 1 tumours affected primarily younger females; male: female ratios were respectively 0.61 (median age 2.9 years; 95% CI: 2.4–5.2; p≤ 0.005), 1.25 (median age 7.9 years; 95% CI: 6–9.7) and 1.63 (median age 5.9 years; 95% CI: 4.9–7.8) for group 1, 2 and 3 patients. Overall outcome was poorest in group 1 patients which had a median survival of 0.8 years (95% CI: 0.47–1.2; p=0.019) as compared to 1.8 years (95% CI: 1.4–2.3) and 4.3 years; (95% CI: 0.82–7.8) respectively for group 2 and 3 patients. Group 3 tumours had the highest incidence of metastases at diagnosis; M0: M+ ratio were respectively 0.9 and 3.9 for group 3, versus group 1 and 2 tumours combined (p=0.037). Interpretation LIN28 and OLIG2 represent highly promising, novel diagnostic and prognostic molecular markers for CNS PNET that warrants further evaluation in prospective clinical trials. PMID:22691720

  3. Effect of central muscarinic receptors on passive-avoidance learning deficits induced by prenatal pentylenetetrazol kindling in male offspring.

    Science.gov (United States)

    Pourmotabbed, A; Mahmoodi, G; Mahmoodi, S; Mohammadi-Farani, A; Nedaei, S E; Pourmotabbed, T; Pourmotabbed, T

    2014-10-24

    Occurrence of the epileptic seizures during gestation might affect the neurodevelopment of the fetus resulting in cognitive problems for the child later in life. We have previously reported that prenatal pentylenetetrazol (PTZ)-kindling induces learning and memory deficits in the children born to kindled mothers, later in life but the mechanisms involved in this processes are unknown. The cholinergic system plays a major role in learning and memory. The present study was performed to investigate the possible involvement of central muscarinic cholinergic receptors on learning and memory deficits induced by prenatal PTZ-kindling in male offspring. Pregnant Wistar rats were kindled by repetitive i.p. injection of 25mg/kg of PTZ on day 13 of their pregnancy. The effect of intracerebroventricular (ICV) microinjection of scopolamine and pilocarpine, muscarinic cholinergic receptors antagonist and agonist, respectively on passive-avoidance learning of pups were tested at 12weeks of age using shuttle-box apparatus. Our data showed that the retention latencies of pups that received scopolamine (2 or 3μg) were significantly reduced compared to those received normal saline (pkindled dams and suggest a central mechanism for the cognitive and memory dysfunction, associated with seizures during pregnancy.

  4. CENTRAL PLATEAU REMEDIATION

    Energy Technology Data Exchange (ETDEWEB)

    ROMINE, L.D.

    2006-02-01

    A systematic approach to closure planning is being implemented at the Hanford Site's Central Plateau to help achieve the goal of closure by the year 2035. The overall objective of Central Plateau remediation is to protect human health and the environment from the significant quantity of contaminated material that resulted from decades of plutonium production in support of the nation's defense. This goal will be achieved either by removing contaminants or placing the residual contaminated materials in a secure configuration that minimizes further migration to the groundwater and reduces the potential for inadvertent intrusion into contaminated sites. The approach to Central Plateau cleanup used three key concepts--closure zones, closure elements, and closure process steps--to create an organized picture of actions required to complete remediation. These actions were merged with logic ties, constraints, and required resources to produce an integrated time-phased schedule and cost profile for Central Plateau closure. Programmatic risks associated with implementation of Central Plateau closure were identified and analyzed. Actions to mitigate the most significant risks are underway while high priority remediation projects continue to make progress.

  5. Integration of Three-dimensional Traffic in Public Space of Urban Central Areas: A Case Study of Rail Transport Hub and Central Business District%大城市中心区公共空间立体化交通的整合——以轨道交通枢纽和中央商务区为例

    Institute of Scientific and Technical Information of China (English)

    赵景伟

    2013-01-01

    随着大城市中心区土地的高度集约化利用,城市公共空间由于汇集了多种类型的交通需求而成为交通问题复杂、空间环境难以改善的城市区域.城市轨道交通枢纽和中央商务区作为大城市公共空间的典型代表,其空间特征确定了立体化交通方式整合的类型与方法.通过对城市公共空间多样性、有序性、和谐性的分析,提出了公共交通整合与步行系统整合是实现公共空间立体化的两个重要内容.公共空间立体化交通方式的整合,不仅能够实现人与机动车的分流,改善人流密集型公共空间的交通秩序,还可以保证城市公共空间的各项功能稳定、集约、高效运转,提升城市公众生活的品质,增强城市空间的链接,创建高质量的城市空间环境.%With the highly intensive use of land in urban central areas,the urban public space becomes the area where traffic problems are the most complex and the environment is hard to be improved due to assembling various types of traffic demands.The public space of rail transport hub and central business district,as the typical example of urban public space,confirms the type and method of three-dimensional traffic integration.The analysis on diversity,order and harmony of urban public space was made to draw a conclusion that the public transport integration and pedestrian transport integration are two keys for the three-dimensional treatment for the public space.The traffic integration can not only separate the human walk from motor vehicles running,which improves the traffic order in crowed space,but ensure all functions to be stable,intensive and efficient.It shall promote the quality of public life,increase the space links,and obtain an environment friendly space.

  6. Treatment of beta amyloid 1–42 (Aβ1–42)-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo

    Science.gov (United States)

    Kwakowsky, Andrea; Potapov, Kyoko; Kim, SooHyun; Peppercorn, Katie; Tate, Warren P.; Ábrahám, István M.

    2016-01-01

    In Alzheimer’s disease (AD), there is a loss in cholinergic innervation targets of basal forebrain which has been implicated in substantial cognitive decline. Amyloid beta peptide (Aβ1–42) accumulates in AD that is highly toxic for basal forebrain cholinergic (BFC) neurons. Although the gonadal steroid estradiol is neuroprotective, the administration is associated with risk of off-target effects. Previous findings suggested that non-classical estradiol action on intracellular signaling pathways has ameliorative potential without estrogenic side effects. After Aβ1–42 injection into mouse basal forebrain, a single dose of 4-estren-3α, 17β-diol (estren), the non-classical estradiol pathway activator, restored loss of cholinergic cortical projections and also attenuated the Aβ1–42-induced learning deficits. Estren rapidly and directly phosphorylates c-AMP-response–element-binding-protein and extracellular-signal-regulated-kinase-1/2 in BFC neurons and restores the cholinergic fibers via estrogen receptor-α. These findings indicated that selective activation of non-classical intracellular estrogen signaling has a potential to treat the damage of cholinergic neurons in AD. PMID:26879842

  7. The mediation of the central histaminergic system in the pressor effect of intracerebroventricularly injected melittin, a phospholipase A2 activator, in normotensive rats.

    Science.gov (United States)

    Altinbas, Burcin; Topuz, Bora B; Yilmaz, Mustafa S; Aydin, Cenk; Savci, Vahide; Jochem, Jerzy; Aydin, Sami; Yalcin, Murat

    2012-01-01

    Melittin is a polypeptide component of bee venom that leads to an increase in arachidonic acid release and subsequently in prostaglandin synthesis by activating phospholipase A(2). Recently we demonstrated that centrally or peripherally administrated melittin caused pressor effect and central thromboxane A(2) (TXA(2)) and cholinergic system mediated these effects of melittin. Also centrally injected histamine leads to pressor and bradycardic response by activating central histamine receptors in normotensive rats and central cholinergic system involved the effects of histamine. The present study demonstrates an involvement of the central histaminergic system in melittin-induced cardiovascular effect in normotensive rats. Experiments were carried out in male Sprague Dawley rats. Intracerebroventricularly (i.c.v.) injected melittin (0.5, 1 and 2 nmol) caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR) as we reported previously. Moreover, H(2) receptor antagonist ranitidine (50 nmol; i.c.v.) almost completely and H(3)/H(4) receptor antagonist thioperamide (50 nmol; i.c.v.) partly blocked melittin-evoked cardiovascular effects, whereas H(1) receptor blocker chlorpheniramine (50 nmol; i.c.v.) had no effect. Also centrally injected melittin was accompanied by 28% increase in extracellular histamine concentration in the posterior hypothalamus, as shown in microdialysis studies. In conclusion, results show that centrally administered melittin causes pressor and bradycardic response in conscious rats. Moreover, according to our findings, there is an involvement of the central histaminergic system in melittin-induced cardiovascular effects.

  8. Paleogene biomarker records from the central Arctic Ocean (Integrated Ocean Drilling Program Expedition 302): Organic carbon sources, anoxia, and sea surface temperature

    Science.gov (United States)

    Weller, Petra; Stein, Ruediger

    2008-03-01

    During Integrated Ocean Drilling Program Expedition 302 (Arctic Coring Expedition (ACEX)) a more than 200 m thick sequence of Paleogene organic carbon (OC)-rich (black shale type) sediments was drilled. Here we present new biomarker data determined in ACEX sediment samples to decipher processes controlling OC accumulation and their paleoenvironmental significance during periods of Paleogene global warmth and proposed increased freshwater discharge in the early Cenozoic. Specific source-related biomarkers including n-alkanes, fatty acids, isoprenoids, carotenoids, hopanes/hopenes, hopanoic acids, aromatic terpenoids, and long-chain alkenones show a high variability of components, derived from marine and terrestrial origin. The distribution of hopanoic acid isomers is dominated by compounds with the biological 17β(H), 21β(H) configuration indicating a low level of maturity. On the basis of the biomarker data the terrestrial OC supply was significantly enriched during the late Paleocene and part of the earliest Eocene, whereas increased aquatic contributions and euxinic conditions of variable intensity were determined for the Paleocene-Eocene thermal maximum and Eocene thermal maximum 2 events as well as the middle Eocene time interval. Furthermore, samples from the middle Eocene are characterized by the occurrence of long-chain alkenones, high proportions of lycopane, and high ratios (>0.6) of (n-C35 + lycopane)/n-C31. The occurrence of C37-alkenenones, which were first determined toward the end of the Azolla freshwater event, indicates that the OC becomes more marine in origin during the middle Eocene. Preliminary U37K'-based sea surface temperature (SST) values display a long-term temperature decrease of about 15°C during the time interval 49-44.5 Ma (25° to 10°C), coinciding with the global benthic δ18O cooling trend after the early Eocene climatic optimum. At about 46 Ma, parallel with onset of ice-rafted debris, SST (interpreted as summer temperatures

  9. Preliminary integrated geologic map databases for the United States: Digital data for the generalized bedrock geologic map, Yukon Flats region, east-central Alaska

    Science.gov (United States)

    Till, Alison B.; Dumoulin, Julie A.; Phillips, Jeffrey D.; Stanley, Richard G.; Crews, Jessie

    2006-01-01

    The growth in the use of Geographic Information Systems (GIS) has highlighted the need for digital geologic maps that have been attributed with information about age and lithology. Such maps can be conveniently used to generate derivative maps for manifold special purposes such as mineral-resource assessment, metallogenic studies, tectonic studies, and environmental research. This report is part of a series of integrated geologic map databases that cover the entire United States. Three national-scale geologic maps that portray most or all of the United States already exist; for the conterminous U.S., King and Beikman (1974a,b) compiled a map at a scale of 1:2,500,000, Beikman (1980) compiled a map for Alaska at 1:2,500,000 scale, and for the entire U.S., Reed and others (2005a,b) compiled a map at a scale of 1:5,000,000. A digital version of the King and Beikman map was published by Schruben and others (1994). Reed and Bush (2004) produced a digital version of the Reed and others (2005a) map for the conterminous U.S. The present series of maps is intended to provide the next step in increased detail. State geologic maps that range in scale from 1:100,000 to 1:1,000,000 are available for most of the country, and digital versions of these state maps are the basis of this product. The digital geologic maps presented here are in a standardized format as ARC/INFO export files and as ArcView shape files. Data tables that relate the map units to detailed lithologic and age information accompany these GIS files. The map is delivered as a set 1:250,000-scale quadrangle files. To the best of our ability, these quadrangle files are edge-matched with respect to geology. When the maps are merged, the combined attribute tables can be used directly with the merged maps to make derivative maps.

  10. Integrated interpretation of satellite imagery, aeromagnetic, aeroradiometric and ground exploration data-sets to delineate favorable target zones for unconformity related uranium mineralization, Khariar Basin, Central India

    International Nuclear Information System (INIS)

    The Mesoproterozoic Khariar basin, to the SE of Chhattisgarh basin, comprises 1000 m thick arenaceous-argillaceous sediments. For the first time, a multidisciplinary approach has been made to the integrate interpreted satellite imagery, aero-magnetic and aero-radiometric data with available ground exploration data sets with an objective to understand structural fabric and to establish various parameters for unconformity related uranium mineralization in the environs of Khariar basin. Total Magnetic Intensity (TMI) anomaly image has been useful to mark major faults (ENE-WSW), magnetic bodies and overall basement characteristics. Combination of first vertical derivative (1VD) and tilt derivative magnetic images brought out presence of NW-SE magnetic linear (dominant) with minor ENE-WSW and NNE-SSW trends. Basic dykes and quartz veins are the surface manifestations of NW-SE trend in basement. Radially averaged power spectrum indicates the approximate basement configuration. Enhanced Thematic Mapper satellite imagery (Landsat ETM+) interpretation has shown lineaments along NW-SE, NNE-SSW, ENE-WSW and ENW-WSE directions. These observations are corroborated by interpreted results of magnetic data. Analysis of both results indicate NW-SE and ENE-WSW trends as post depositional. Aero-radiometric images (U, Th, K and ternary U-Th-K) show overall radio-elemental distribution for various litho-units. Besides, Th and K images along with interpreted ETM+ satellite imagery (RGB: 432/752/751) are useful to map small outliers and to modify basement-sediment contact. Geochemical data from basement rocks around Khariar basin suggests the younger Bundeli granitoids and its equivalents are good source of uranium in the western margin. Presence of labile uranium is inferred from higher concentration of uranium in water samples. The Airborne gamma-ray spectrometry (AGRS) and hydro-geochemical anomalies fall along fault zones and intersection of fault zones. The western and southern

  11. Cholinergic Enhancement of Brain Activation in Mild Cognitive Impairment (MCI during Episodic Memory Encoding

    Directory of Open Access Journals (Sweden)

    Shannon L Risacher

    2013-09-01

    Full Text Available Objective: To determine the physiological impact of treatment with donepezil (Aricept on neural circuitry supporting episodic memory encoding in patients with amnestic mild cognitive impairment (MCI using functional MRI (fMRI. Methods: 18 patients with MCI and 20 age-matched healthy controls (HC were scanned twice while performing an event-related verbal episodic encoding task. MCI participants were scanned before treatment and after approximately 3 months on donepezil; HC were untreated but rescanned at the same interval. Voxel-level analyses assessed treatment effects in activation profile relative to retest changes in non-treated HC. Changes in task-related connectivity in medial temporal circuitry were also evaluated, as were associations between brain activation pattern, task-related functional connectivity, task performance, and clinical measures of cognition.Results: At baseline, the MCI group showed reduced activation during encoding relative to HC in the right medial temporal lobe (MTL; hippocampal/parahippocampal and additional regions, as well as attenuated task-related deactivation, relative to rest, in a medial parietal lobe cluster. After treatment, the MCI group showed normalized MTL activation and improved parietal deactivation. These changes were associated with cognitive performance. After treatment, the MCI group also demonstrated increased task-related functional connectivity from the right MTL cluster seed region to a network of other sites including the basal nucleus/caudate and bilateral frontal lobes. Increased functional connectivity was associated with improved task performance.Conclusions: Pharmacologic enhancement of cholinergic function in amnestic MCI is associated with changes in brain activation pattern and functional connectivity during episodic memory processing which are in turn related to increased cognitive performance. fMRI is a promising biomarker for assessing treatment related changes in brain function.

  12. Nitric oxide activates leak K+ currents in the presumed cholinergic neuron of basal forebrain.

    Science.gov (United States)

    Kang, Youngnam; Dempo, Yoshie; Ohashi, Atsuko; Saito, Mitsuru; Toyoda, Hiroki; Sato, Hajime; Koshino, Hisashi; Maeda, Yoshinobu; Hirai, Toshihiro

    2007-12-01

    Learning and memory are critically dependent on basal forebrain cholinergic (BFC) neuron excitability, which is modulated profoundly by leak K(+) channels. Many neuromodulators closing leak K(+) channels have been reported, whereas their endogenous opener remained unknown. We here demonstrate that nitric oxide (NO) can be the endogenous opener of leak K(+) channels in the presumed BFC neurons. Bath application of 1 mM S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, induced a long-lasting hyperpolarization, which was often interrupted by a transient depolarization. Soluble guanylyl cyclase inhibitors prevented SNAP from inducing hyperpolarization but allowed SNAP to cause depolarization, whereas bath application of 0.2 mM 8-bromoguanosine-3',5'-cyclomonophosphate (8-Br-cGMP) induced a similar long-lasting hyperpolarization alone. These observations indicate that the SNAP-induced hyperpolarization and depolarization are mediated by the cGMP-dependent and -independent processes, respectively. When examined with the ramp command pulse applied at -70 mV under the voltage-clamp condition, 8-Br-cGMP application induced the outward current that reversed at K(+) equilibrium potential (E(K)) and displayed Goldman-Hodgkin-Katz rectification, indicating the involvement of voltage-independent K(+) current. By contrast, SNAP application in the presumed BFC neurons either dialyzed with the GTP-free internal solution or in the presence of 10 muM Rp-8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate sodium salt, a protein kinase G (PKG) inhibitor, induced the inward current that reversed at potentials much more negative than E(K) and close to the reversal potential of Na(+)-K(+) pump current. These observations strongly suggest that NO activates leak K(+) channels through cGMP-PKG-dependent pathway to markedly decrease the excitability in BFC neurons, while NO simultaneously causes depolarization by the inhibition of Na(+)-K(+) pump through ATP

  13. Formation and Dynamics of Waves in a Cortical Model of Cholinergic Modulation.

    Directory of Open Access Journals (Sweden)

    James P Roach

    2015-08-01

    Full Text Available Acetylcholine (ACh is a regulator of neural excitability and one of the neurochemical substrates of sleep. Amongst the cellular effects induced by cholinergic modulation are a reduction in spike-frequency adaptation (SFA and a shift in the phase response curve (PRC. We demonstrate in a biophysical model how changes in neural excitability and network structure interact to create three distinct functional regimes: localized asynchronous, traveling asynchronous, and traveling synchronous. Our results qualitatively match those observed experimentally. Cortical activity during slow wave sleep (SWS differs from that during REM sleep or waking states. During SWS there are traveling patterns of activity in the cortex; in other states stationary patterns occur. Our model is a network composed of Hodgkin-Huxley type neurons with a M-current regulated by ACh. Regulation of ACh level can account for dynamical changes between functional regimes. Reduction of the magnitude of this current recreates the reduction in SFA the shift from a type 2 to a type 1 PRC observed in the presence of ACh. When SFA is minimal (in waking or REM sleep state, high ACh patterns of activity are localized and easily pinned by network inhomogeneities. When SFA is present (decreasing ACh, traveling waves of activity naturally arise. A further decrease in ACh leads to a high degree of synchrony within traveling waves. We also show that the level of ACh determines how sensitive network activity is to synaptic heterogeneity. These regimes may have a profound functional significance as stationary patterns may play a role in the proper encoding of external input as memory and traveling waves could lead to synaptic regularization, giving unique insights into the role and significance of ACh in determining patterns of cortical activity and functional differences arising from the patterns.

  14. Cytokines and cholinergic signals co-modulate surgical stress-induced changes in mood and memory.

    Science.gov (United States)

    Shapira-Lichter, Irit; Beilin, Benzion; Ofek, Keren; Bessler, Hanna; Gruberger, Michal; Shavit, Yehuda; Seror, Dan; Grinevich, Galina; Posner, Eldad; Reichenberg, Abraham; Soreq, Hermona; Yirmiya, Raz

    2008-03-01

    Inflammatory cytokines and the cholinergic system have been implicated in the effects of stressors on mood and memory; however, the underlying mechanisms involved and the potential interrelationships between these pathways remain unclear. To address these questions, we administered neuropsychological tests to 33 generally healthy surgery patients who donated blood samples several days prior to undergoing moderate surgery (baseline), on the morning of the surgery (i.e., a psychological stressor), and one day after surgery. Eighteen control subjects were similarly tested. Serum levels of inflammatory cytokines, acetylcholinesterase (AChE) activity, and the stressor-inducible AChE-R variant were measured. An elevation in anxiety levels, an increase in depressed mood, and a decline in declarative memory were observed on the morning of the surgery, prior to any medical intervention, and were exacerbated one day after surgery. The surgical stressor-induced elevated IL-1 beta levels, which contributed to the increased depressed mood and to the post-surgery increase in AChE-R expression. The latter increase, which was also predicted by pre-surgery AChE-R and post-surgery mood disturbances, was associated with exacerbated memory impairments induced by surgery. In addition, elevated levels of AChE-R on the morning of the surgery predicted the post-surgery elevation in IL-6 levels, which was associated with amelioration of the memory impairments induced by surgery. Taken together, these findings suggest that exposure to a surgical stressor induces a reciprocal up-regulation of AChE-R and pro-inflammatory cytokines, which are involved in regulating the surgery-induced mood and memory disturbances.

  15. Adrenergic and cholinergic activity contributes to the cardiovascular effects of lionfish (Pterois volitans) venom.

    Science.gov (United States)

    Church, Jarrod E; Hodgson, Wayne C

    2002-06-01

    The aim of the present study was to further investigate the cardiovascular activity of Pterois volitans crude venom. Venom (0.6-18 microg protein/ml) produced dose- and endothelium-dependent relaxation in porcine coronary arteries that was potentiated by atropine (10nM), but significantly attenuated by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (NOLA; 0.1mM), by prior exposure of the tissue to stonefish antivenom (SFAV, 3 units/ml, 10 min), or by removal of extracellular Ca(2+). In rat paced left atria, venom (10 microg protein/ml) produced a decrease, followed by an increase, in contractile force. Atropine (0.5 microM) abolished the decrease in force and potentiated the increase. Propranolol (5 microM) did not affect the decrease in force but significantly attenuated the increase. In spontaneously beating right atria, venom (10 microg protein/ml) produced an increase in rate that was significantly attenuated by propranolol (5 microM). Prior incubation with SFAV (0.3 units/microg protein, 10 min) abolished both the inotropic and chronotropic responses to venom. In the anaesthetised rat, venom (100 micro protein/kg, i.v.) produced a pressor response, followed by a sustained depressor response. Atropine (1mg/kg, i.v.) potentiated the pressor response. The further addition of prazosin (50 microg/kg, i.v.) restored the original response to venom. Prior administration of SFAV (100 units/kg, i.v., 10 min) significantly attenuated the in vivo response to venom. It is concluded that P. volitans venom produces its cardiovascular effects primarily by acting on muscarinic cholinergic receptors and adrenoceptors. As SFAV neutralised many of the effects of P. volitans venom, we suggest that the two venoms share a similar component(s). PMID:12175616

  16. Reciprocal cholinergic and GABAergic modulation of the small ventrolateral pacemaker neurons of Drosophila's circadian clock neuron network.

    Science.gov (United States)

    Lelito, Katherine R; Shafer, Orie T

    2012-04-01

    The relatively simple clock neuron network of Drosophila is a valuable model system for the neuronal basis of circadian timekeeping. Unfortunately, many key neuronal classes of this network are inaccessible to electrophysiological analysis. We have therefore adopted the use of genetically encoded sensors to address the physiology of the fly's circadian clock network. Using genetically encoded Ca(2+) and cAMP sensors, we have investigated the physiological responses of two specific classes of clock neuron, the large and small ventrolateral neurons (l- and s-LN(v)s), to two neurotransmitters implicated in their modulation: acetylcholine (ACh) and γ-aminobutyric acid (GABA). Live imaging of l-LN(v) cAMP and Ca(2+) dynamics in response to cholinergic agonist and GABA application were well aligned with published electrophysiological data, indicating that our sensors were capable of faithfully reporting acute physiological responses to these transmitters within single adult clock neuron soma. We extended these live imaging methods to s-LN(v)s, critical neuronal pacemakers whose physiological properties in the adult brain are largely unknown. Our s-LN(v) experiments revealed the predicted excitatory responses to bath-applied cholinergic agonists and the predicted inhibitory effects of GABA and established that the antagonism of ACh and GABA extends to their effects on cAMP signaling. These data support recently published but physiologically untested models of s-LN(v) modulation and lead to the prediction that cholinergic and GABAergic inputs to s-LN(v)s will have opposing effects on the phase and/or period of the molecular clock within these critical pacemaker neurons.

  17. Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway

    Institute of Scientific and Technical Information of China (English)

    Xiaojie Liu; Zhigang Mei; Jingping Qian; Yongbao Zeng; Mingzhi Wang

    2013-01-01

    Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen), has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that an-ti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic an-ti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be in-volved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment (intravenous injection) re-duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-αin brain tissue. Pretreatment with puerarin (intravenous injection) attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) activation and nuclear factor kappa B (NF-κB) inhibition. These observa-tions were inhibited by the alpha7 nicotinic acetylcholine receptor (α7nAchR) antagonistα-bungarotoxin (α-BGT). In addition, puerarin pretreatment increased the expression of α7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re-sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be me-diated through the activation of the cholinergic anti-inflammatory pathway.

  18. Vitamin D₃ improves decline in cognitive function and cholinergic transmission in prefrontal cortex of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Alrefaie, Zienab; Alhayani, Abdulmone'em

    2015-01-01

    Complications of diabetes mellitus include cognitive impairments and functional changes in the brain. The present study aimed to investigate the possible beneficial effect of vitamin D3 on episodic memory and cholinergic transmission in the prefrontal cortex of streptozotocin-induced diabetic rats. Thirty male Wistar rats (150-200 g) were included into control, diabetic and diabetic supplemented with vitamin D3 groups. Diabetes was induced by single intraperitoneal injection of streptozotocin 45 mg/kg in citrate buffer. Vitamin D3 was administered orally in a dose of 500 IU/kg/day in corn oil for 10 weeks. Then rats were subjected to novel object recognition test to examine for episodic memory. Animals were sacrificed under diethyl ether anesthesia and prefrontal cortices were dissected to measure the activity of choline acetyl transferase (CAT) and acetyle choline esterase (ACE) enzymes to assess for cholinergic transmission. Diabetic rats spent significantly less time exploring the novel object compared to control animals. Vitamin D3 significantly attenuated the diabetes-induced impairment so that animals again spent significantly more time exploring the novel object. The CAT activity was significantly decreased in diabetic animals while the ACE activity was significantly increased compared to control non-diabetic animals. Diabetes-induced alterations in enzyme activity in the prefrontal cortex were mitigated by vitamin D3 supplementation. The present findings demonstrate the potential effect of vitamin D3 supplementation on cognitive function in diabetic animals. It is possible that this effect is mediated through enhancing the prefrontal cortex cholinergic transmission. PMID:25835318

  19. Impairment of cognitive function and reduced hippocampal cholinergic activity in a rat model of chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    Chunling Zhao; Yan Chen; Chunlai Zhang; Linya Lü; Qian Xu

    2011-01-01

    The present study established a rat model of chronic intermittent hypoxia (CIH) to simulate obstructive sleep apnea syndrome. CIH rats were evaluated for cognitive function using the Morris water maze, and neuronal pathology in the hippocampus was observed using hematoxylin-eosin staining. In addition, hippocampal choline acetyl transferase (ChAT) and nicotinic acetylcholine receptor (nAChR) expression was determined by immunohistochemistry. Our results revealed necrotic hippocampal neurons, decreased ChAT and nAChR expression, as well as cognitive impairment in CIH rats. These results suggest that hippocampal neuronal necrosis and decreased cholinergic activity may be involved in CIH-induced cognitive impairment in rats.

  20. Distributed trace using central performance counter memory

    Science.gov (United States)

    Satterfield, David L.; Sexton, James C.

    2013-01-22

    A plurality of processing cores, are central storage unit having at least memory connected in a daisy chain manner, forming a daisy chain ring layout on an integrated chip. At least one of the plurality of processing cores places trace data on the daisy chain connection for transmitting the trace data to the central storage unit, and the central storage unit detects the trace data and stores the trace data in the memory co-located in with the central storage unit.

  1. c-fos Expression in mesopontine noradrenergic and cholinergic neurons of the cat during carbachol-induced active sleep: a double-labeling study.

    Science.gov (United States)

    Yamuy, J; Sampogna, S; Morales, F R; Chase, M H

    1998-01-01

    The interaction of cholinergic and catecholaminergic mechanisms in the mesopontine region has been hypothesized as being critical for the generation and maintenance of active (REM) sleep. To further examine this hypothesis, we sought to determine the pattern of neuronal activation (via c-fos expression) of catecholaminergic and cholinergic neurons in this region during active sleep induced by the pontine microapplication of carbachol (designated as active sleep-carbachol). Accordingly, we used two sets of double-labeling techniques; the first to identify tyrosine hydroxylase-containing neurons (putative catecholaminergic cells) which also express the c-fos protein product Fos, and the second to reveal choline acetyltransferase-containing neurons (putative cholinergic cells) which also express Fos. Compared to control cats, active sleep-carbachol cats exhibited a significantly greater number of Fos-expressing neurons in the dorsolateral region of the pons, which encompasses the locus coeruleus, the lateral pontine reticular formation, the peribrachial nuclei and the latero-dorsal and pedunculo-pontine tegmental nuclei. However, both control and active sleep-carbachol cats exhibited a similar number of catecholaminergic and cholinergic neurons in those regions that expressed Fos (i.e., double-labeled cells). A large number of c-fos-expressing neurons in the active sleep-carbachol cats whose neurotransmitter phenotype was not identified suggests that non-catecholaminergic, non-cholinergic neuronal populations in mesopontine regions are involved in the generation and maintenance of active sleep. The lack of increased c-fos expression in catecholaminergic neurons during active sleep-carbachol confirms and extends previous data that indicate that these cells are silent during active sleep-carbachol and naturally-occurring active sleep. The finding that cholinergic neurons of the dorsolateral pons were not activated either during wakefulness or active sleep

  2. Discharge Profiles across the Sleep–Waking Cycle of Identified Cholinergic, GABAergic, and Glutamatergic Neurons in the Pontomesencephalic Tegmentum of the Rat

    Science.gov (United States)

    Boucetta, Soufiane; Cissé, Youssouf; Mainville, Lynda; Morales, Marisela

    2014-01-01

    Distributed within the laterodorsal tegmental and pedunculopontine tegmental nuclei (LDT and PPT), cholinergic neurons in the pontomesencephalic tegmentum have long been thought to play a critical role in stimulating cortical activation during waking (W) and paradoxical sleep (PS, also called REM sleep), yet also in promoting PS with muscle atonia. However, the discharge profile and thus precise roles of the cholinergic neurons have remained uncertain because they lie intermingled with GABAergic and glutamatergic neurons, which might also assume these roles. By applying juxtacellular recording and labeling in naturally sleeping–waking, head-fixed rats, we investigated the discharge profiles of histochemically identified cholinergic, GABAergic, and glutamatergic neurons in the LDT, SubLDT, and adjoining medial part of the PPT (MPPT) in relation to sleep–wake states, cortical activity, and muscle tone. We found that all cholinergic neurons were maximally active during W and PS in positive correlation with fast (γ) cortical activity, as “W/PS-max active neurons.” Like cholinergic neurons, many GABAergic and glutamatergic neurons were also “W/PS-max active.” Other GABAergic and glutamatergic neurons were “PS-max active,” being minimally active during W and maximally active during PS in negative correlation with muscle tone. Conversely, some glutamatergic neurons were “W-max active,” being maximally active during W and minimally active during PS in positive correlation with muscle tone. Through different discharge profiles, the cholinergic, GABAergic, and glutamatergic neurons of the LDT, SubLDT, and MPPT thus appear to play distinct roles in promoting W and PS with cortical activation, PS with muscle atonia, or W with muscle tone. PMID:24672016

  3. Discharge profiles across the sleep-waking cycle of identified cholinergic, GABAergic, and glutamatergic neurons in the pontomesencephalic tegmentum of the rat.

    Science.gov (United States)

    Boucetta, Soufiane; Cissé, Youssouf; Mainville, Lynda; Morales, Marisela; Jones, Barbara E

    2014-03-26

    Distributed within the laterodorsal tegmental and pedunculopontine tegmental nuclei (LDT and PPT), cholinergic neurons in the pontomesencephalic tegmentum have long been thought to play a critical role in stimulating cortical activation during waking (W) and paradoxical sleep (PS, also called REM sleep), yet also in promoting PS with muscle atonia. However, the discharge profile and thus precise roles of the cholinergic neurons have remained uncertain because they lie intermingled with GABAergic and glutamatergic neurons, which might also assume these roles. By applying juxtacellular recording and labeling in naturally sleeping-waking, head-fixed rats, we investigated the discharge profiles of histochemically identified cholinergic, GABAergic, and glutamatergic neurons in the LDT, SubLDT, and adjoining medial part of the PPT (MPPT) in relation to sleep-wake states, cortical activity, and muscle tone. We found that all cholinergic neurons were maximally active during W and PS in positive correlation with fast (γ) cortical activity, as "W/PS-max active neurons." Like cholinergic neurons, many GABAergic and glutamatergic neurons were also "W/PS-max active." Other GABAergic and glutamatergic neurons were "PS-max active," being minimally active during W and maximally active during PS in negative correlation with muscle tone. Conversely, some glutamatergic neurons were "W-max active," being maximally active during W and minimally active during PS in positive correlation with muscle tone. Through different discharge profiles, the cholinergic, GABAergic, and glutamatergic neurons of the LDT, SubLDT, and MPPT thus appear to play distinct roles in promoting W and PS with cortical activation, PS with muscle atonia, or W with muscle tone. PMID:24672016

  4. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

    International Nuclear Information System (INIS)

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

  5. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Department of Environmental Science, New York Medical College, Valhalla, NY (United States); Heindel, Ned D. [Department of Chemistry, Lehigh University, Bethlehem, PA (United States); Young, Sherri C. [Department of Chemistry, Muhlenberg College, Allentown, PA (United States); Sinko, Patrick J. [Department of Pharmaceutics, Rutgers University, Piscataway, NJ (United States); Casillas, Robert P. [MRIGlobal, Kansas City, MO (United States); Laskin, Jeffrey D. [Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Gerecke, Donald R., E-mail: gerecke@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States)

    2014-10-15

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

  6. Evidence against VIP or substance P being the transmitter in non-cholinergic excitatory nerves supplying the guinea-pig bladder.

    Science.gov (United States)

    Meldrum, L A; Burnstock, G

    1985-06-01

    In the guinea-pig bladder, contractile responses to substance P (0.3 microM) and VIP (3 microM) were unaffected by P2-purinoceptor desensitization with alpha,beta-methylene ATP (3 X 10(-6) M), while the responses to stimulation of the non-cholinergic excitatory nerves (4-16 Hz) were abolished. The evidence presented suggests that ATP or a related purine nucleotide, and not VIP or substance P, is responsible for the non-cholinergic excitatory component of the nerve-mediated response.

  7. Cuidados com cateter central de inserção periférica no neonato: revisão integrativa da literatura Cuidados con catéter central de inserción periférica en el neonato: revisión integrativa de la literatura Peripherally inserted central catheter care in neonates: an integrative literature review

    OpenAIRE

    Derdried Athanasio Johann; Luciana Souza Marques De Lazzari; Edivane Pedrolo; Priscila Mingorance; Tatiana Queiroz Ribeiro de Almeida; Mitzy Tannia Reichembach Danski

    2012-01-01

    O cateter central de inserção periférica é tecnologia comum empregada na terapia intravenosa de neonatos. Trata-se de revisão integrativa, cujo objetivo foi investigar e analisar as evidências disponíveis na literatura acerca da temática. As bases de dados pesquisadas foram Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Biblioteca Nacional de Medicina dos Estados Unidos (PubMed). Resultados apontam lacunas no que tange à população neonatal; conhecimento insuficiente d...

  8. central t

    Directory of Open Access Journals (Sweden)

    Manuel R. Piña Monarrez

    2007-01-01

    Full Text Available Dado que la Regresión Ridge (RR, es una estimación sesgada que parte de la solución de la regresión de Mínimos Cuadrados (MC, es vital establecer las condiciones para las que la distribución central t de Student que se utiliza en la prueba de hipótesis en MC, sea también aplicable a la regresión RR. La prueba de este importante resultado se presenta en este artículo.

  9. Do different neurons age differently? Direct genome-wide analysis of aging in single identified cholinergic neurons

    Directory of Open Access Journals (Sweden)

    Leonid L Moroz

    2010-05-01

    Full Text Available Aplysia californica is a powerful experimental system to study the entire scope of genomic and epigenomic regulation at the resolution of single functionally characterized neurons and is an emerging model in the neurobiology of aging. First, we have identified and cloned a number of evolutionarily conserved genes that are age-related, including components of apoptosis and chromatin remodeling. Second, we performed gene expression profiling of different identified cholinergic neurons between young and aged animals. Our initial analysis indicates that two cholinergic neurons (R2 and LPl1 revealed highly differential genome-wide changes following aging suggesting that on the molecular scale different neurons indeed age differently. Each of neurons tested has a unique subset of genes differentially expressed in older animals, and the majority of differently expressed genes (including those related to apoptosis and Alzheimer’s disease are found in aging neurons of one but not another type. The performed analysis allows us to implicate (i cell specific changes in histones, (ii DNA methylation and (iii regional relocation of RNAs as key processes underlying age-related changes in neuronal functions and synaptic plasticity. These mechanisms can fine-tune the dynamics of long-term chromatin remodeling, or control weakening and the loss of synaptic connections in aging. At the same time our genomic tests revealed evolutionarily conserved gene clusters associated with aging (e.g. apoptosis-, telomere- and redox- dependent processes, insulin and estrogen signaling and water channels.

  10. The Regulatory Action of Radix Astragali on M-Cholinergic Receptor of the Brain of Senile Rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@The changes in density of M-cholinergic receptors in different areas of senile rats and the regulatory action of Huang Qi (黄芪Radix Astragali, a drug for warming yang and replenishing qi) were observed by autoradiography. The results showed that the gray scale displayed in brain sections was clear and mainly distributed in the cortex, hippocampus and striate body, while that due to nonspecific combination was negligible. The gray scale in the cortex, hippocampus and striate body of the experimental group was markedly lower than that in the young control rats, decreased respectively by 24.87%, 14.12% and 12.76% (all P<0.05); but it was obviously higher than those in the senile control rats, increased respectively by 24.15%, 14.38% and 13.47% (P<0.05). The data indicate that Huang Qi (黄芪Radix Astragali) may up-regulate the decreased density of M-cholinergic receptors in the brain of senile rats.

  11. Developmental profile of the aberrant dopamine D2 receptor response in striatal cholinergic interneurons in DYT1 dystonia.

    Directory of Open Access Journals (Sweden)

    Giuseppe Sciamanna

    Full Text Available BACKGROUND: DYT1 dystonia, a severe form of genetically determined human dystonia, exhibits reduced penetrance among carriers and begins usually during adolescence. The reasons for such age dependence and variability remain unclear. METHODS AND RESULTS: We characterized the alterations in D2 dopamine receptor (D2R signalling in striatal cholinergic interneurons at different ages in mice overexpressing human mutant torsinA (hMT. An abnormal excitatory response to the D2R agonist quinpirole was recorded at postnatal day 14, consisting of a membrane depolarization coupled to an increase in spiking frequency, and persisted unchanged at 3 and 9 months in hMT mice, compared to mice expressing wild-type human torsinA and non-transgenic mice. This response was blocked by the D2R antagonist sulpiride and depended upon G-proteins, as it was prevented by intrapipette GDP-β-S. Patch-clamp recordings from dissociated interneurons revealed a significant increase in the Cav2.2-mediated current fraction at all ages examined. Consistently, chelation of intracellular calcium abolished the paradoxical response to quinpirole. Finally, no gross morphological changes were observed during development. CONCLUSIONS: These results suggest that an imbalanced striatal dopaminergic/cholinergic signaling occurs early in DYT1 dystonia and persists along development, representing a susceptibility factor for symptom generation.

  12. Impairment of ATP hydrolysis decreases adenosine A1 receptor tonus favoring cholinergic nerve hyperactivity in the obstructed human urinary bladder.

    Science.gov (United States)

    Silva-Ramos, M; Silva, I; Faria, M; Magalhães-Cardoso, M T; Correia, J; Ferreirinha, F; Correia-de-Sá, P

    2015-12-01

    This study was designed to investigate whether reduced adenosine formation linked to deficits in extracellular ATP hydrolysis by NTPDases contributes to detrusor neuromodulatory changes associated with bladder outlet obstruction in men with benign prostatic hyperplasia (BPH). The kinetics of ATP catabolism and adenosine formation as well as the role of P1 receptor agonists on muscle tension and nerve-evoked [(3)H]ACh release were evaluated in mucosal-denuded detrusor strips from BPH patients (n = 31) and control organ donors (n = 23). The neurogenic release of ATP and [(3)H]ACh was higher (P bladders. Relaxation of detrusor contractions induced by acetylcholine required 30-fold higher concentrations of adenosine. Despite VAChT-positive cholinergic nerves exhibiting higher A(1) immunoreactivity in BPH bladders, the endogenous adenosine tonus revealed by adenosine deaminase is missing. Restoration of A1 inhibition was achieved by favoring (1) ATP hydrolysis with apyrase (2 U mL(-1)) or (2) extracellular adenosine accumulation with dipyridamole or EHNA, as these drugs inhibit adenosine uptake and deamination, respectively. In conclusion, reduced ATP hydrolysis leads to deficient adenosine formation and A(1) receptor-mediated inhibition of cholinergic nerve activity in the obstructed human bladder. Thus, we propose that pharmacological manipulation of endogenous adenosine levels and/or A(1) receptor activation might be useful to control bladder overactivity in BPH patients. PMID:26521170

  13. Molecular imaging of cholinergic processes in prostate cancer using 11C-donepezil and 18F-FEOBV

    International Nuclear Information System (INIS)

    High-grade prostate cancer (PC) displays parasympathetic neoneurogenesis. We investigated the binding of two PET tracers that visualize cholinergic nerves in PC tissue using autoradiography. Prostatectomy tissue was subjected to autoradiography with 11C-donepezil and 18F-FEOBV and correlated with Gleason scores (GS). Regions of interest on the autoradiograms were defined and quantified. Tracer binding in cancer tissue regions was compared with that in normal tissue. We included 13 patients with biopsy-verified PC. In particular, 11C-donepezil uptake was higher in ''high-grade'' PC (GS ≥4 + 3) than in ''low-grade'' PC and benign hyperplasia. 11C-donepezil uptake ranged from a mean of 56 % higher (GS 3 + 3) to 409 % higher (GS 4 + 4), and 18F-FEOBV uptake ranged from 67 % higher (GS 3 + 3) to 194 % higher (GS 4 + 5). The uptake of both tracers was higher in PC with a high GS than in PC with a low GS, but the difference was s