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Sample records for brain cortex neuropeptides

  1. Neuropeptides and the microbiota-gut-brain axis.

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    Holzer, Peter; Farzi, Aitak

    2014-01-01

    Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gut-brain axis. Current efforts in elucidating the implication of neuropeptides in the microbiota-gut-brain axis address four information carriers from the gut to the brain (vagal and spinal afferent neurons; immune mediators such as cytokines; gut hormones; gut microbiota-derived signalling molecules) and four information carriers from the central nervous system to the gut (sympathetic efferent neurons; parasympathetic efferent neurons; neuroendocrine factors involving the adrenal medulla; neuroendocrine factors involving the adrenal cortex). Apart from operating as neurotransmitters, many biologically active peptides also function as gut hormones. Given that neuropeptides and gut hormones target the same cell membrane receptors (typically G protein-coupled receptors), the two messenger roles often converge in the same or similar biological implications. This is exemplified by NPY and peptide YY (PYY), two members of the PP-fold peptide family. While PYY is almost exclusively expressed by enteroendocrine cells, NPY is found at all levels of the gut-brain and brain-gut axis. The function of PYY-releasing enteroendocrine cells is directly influenced by short chain fatty acids generated by the intestinal microbiota from indigestible fibre, while NPY may control the impact of the gut microbiota on inflammatory processes, pain, brain function and behaviour. Although the impact of neuropeptides on the interaction between the gut microbiota and brain awaits to be analysed, biologically active peptides

  2. Expression of neuropeptide Y in rat brain ischemia

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    Babović Siniša S.

    2013-01-01

    Full Text Available Introduction. The immunohistochemical method was used to follow the expression of neuropeptide Y in the course of pre ischemia of the rat brain. The aim of the study was to define all the areas of expression of this protein, show their localization, their map of distribution and histological types. Material and Methods. All the sections of telencephalon, diencephalon and midbrain were studied in resistant, and transitory ischemia, which enabled us to observe the reaction of neurons to an ischemic attack or to repeated attacks. The mapping was done for all three proteins by introducing our results into the maps of rat brain atlas, George Paxinos, Charles Watson. Photographing and protein expression was done using Analysis program. Results. The results of this research show that there is a differens in reaction between the resistant and transitory ischemia groups of rats, especially in the caudoputamen, gyrus dentatus, corpus amygdaloideum, particularly in the medial nucleus. The mapping shows the reaction in caudoputamen, gyrusdentatus, corpus amygdaloideum - especially in the central nucleus, then in the sensitive and secondary auditory cortex, mostly in the laminae V/VI, but less in neuron groups CA1, CA2, CA3 of hippocampus. Discussion. The phylogenetically older parts of the brain-rhinencephalon, also showed reaction, which lead us to conclude that both newer and older brain structures reacted immunohistochemically. Histological data have shown that small neurons are most commonly found while the second most common ones are big pyramidal cells of multipolar and bipolar type, with a different body shape. Conclusion. Our findings have confirmed the results obtained in some rare studies dealing with this issue, and offered a precise and detailed map of cells expressing neuropeptide Y in the rat brain following ischemic attack.

  3. Morphometric characteristics of neuropeptide Y immunoreactive neurons in cortex of human inferior parietal lobule.

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    Krivokuća, Dragan; Puskas, Laslo; Puskas, Nela; Erić, Mirela

    2010-03-01

    The aim of this study was to demonstrate and precisely define the morphology of neurons immunoreactive to neuropeptide Y (NPY) in cortex of human inferior parietal lobule (IPL). Five human brains were used for immunohistochemical investigation of the shape and laminar distribution of NPY neurons in serial section in the supramarginal and angular gyrus. Immunoreactivity to NPY was detected in all six layers of the cortex of human IPL. However a great number of NPY immunoreactive neurons were found in the white matter under the IPL cortex. The following types of NPY immunoreactive neurons were found: Cajal-Retzius, pyramidal, inverted pyramidal, "double bouquet" (bitufted), rare type 6, multipolar nonspinous, bipolar, voluminous "basket", and chandelier cells. These informations about morphometric characteristics of NPY immunoreactive neurons in cortical layers, together with morphometric data taken from brains having schizophrenia or Alzheimer's-type dementia may contribute to better understanding patogenesis of these neurological diseases. The finding of Cajal-Retzius neurons immunoreactive to NPY points to the need for further investigations because of great importance of these cells in neurogenesis and involvement in mentioned diseases instead of their rarity.

  4. Brain neuropeptides in gastric mucosal protection.

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    Gyires, Klára; Zádori, Zoltán S

    2014-12-01

    The centrally induced gastroprotective effect of neuropeptides has been intensively studied. Besides many similarities, however, differences can also be observed in their gastroprotective actions. The gastroprotective dose-response curve proved to be either sigmoid, or bell-shaped. Additional gastrointestinal effects of neuropeptides can contribute to their mucosal protective effect. Part of the neuropeptides induces gastroprotection by peripheral administration as well. Besides vagal nerve the sympathetic nervous system may also be involved in conveying the central effect to the periphery. Better understanding of the complex mechanism of the maintenance of gastric mucosal integrity may result in the development of new strategy to enhance gastric mucosal resistance against injury.

  5. Effects of the Bee Venom Herbal Acupuncture on the Neurotransmitters of the Rat Brain Cortex

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    Hyoung-Seok Yun

    2001-02-01

    Full Text Available In order to study the effects of bee venom Herbal Acupuncture on neurotransmitters in the rat brain cortex, herbal acupuncture with bee venom group and normal saline group was performed at LI4 bilaterally of the rat. the average optical density of neurotransmitters from the cerebral cortex was analysed 30 minutes after the herbal aqupuncture, by the immunohistochemistry. The results were as follows: 1. The density of NADPH-diaphorase in bee venom group was increased significantly at the motor cortex, visual cortex, auditory cortex, cingulate cortex, retrosplenial cortex and perirhinal cortex compared to the normal saline group. 2. The average optical density of vasoactive intestinal peptide in bee venom group had significant changes at the insular cortex, retrosplenial cortex and perirhinal cortex, compared to the normal saline group. 3. The average optical density of neuropeptide-Y in bee venom group increased significantly at the visual cortex and cingulate cortex, compared to the normal saline group.

  6. Brain neuropeptides in central ventilatory and cardiovascular regulation in trout.

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    Jean-Claude eLe Mével

    2012-10-01

    Full Text Available Many neuropeptides and their G-protein coupled receptors (GPCRs are present within the brain area involved in ventilatory and cardiovascular regulation but only a few mammalian studies have focused on the integrative physiological actions of neuropeptides on these vital cardio-respiratory regulations. Because both the central neuroanatomical substrates that govern motor ventilatory and cardiovascular output and the primary sequence of regulatory peptides and their receptors have been mostly conserved through evolution, we have developed a trout model to study the central action of native neuropeptides on cardio-ventilatory regulation. In the present review, we summarize the most recent results obtained using this non-mammalian model with a focus on PACAP, VIP, tachykinins, CRF, urotensin-1, CGRP, angiotensin-related peptides, urotensin-II, NPY, and PYY. We propose hypotheses regarding the physiological relevance of the results obtained.

  7. "Neuropeptides in the brain defense against distant organ damage".

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    Hamasaki, Mike Yoshio; Barbeiro, Hermes Vieira; Barbeiro, Denise Frediani; Cunha, Débora Maria Gomes; Koike, Marcia Kiyomi; Machado, Marcel Cerqueira César; Pinheiro da Silva, Fabiano

    2016-01-15

    Delirium, or acute confusional state, is a common manifestation in diseases that originate outside the central nervous system, affecting 30-40% of elderly hospitalized patients and up to 80% of the critically ill, even though it remains unclear if severe systemic inflammation is able or not to induce cellular disturbances and immune activation in the brain. Neuropeptides are pleotropic molecules heterogeneously distributed throughout the brain and possess a wide spectrum of functions, including regulation of the inflammatory response, so we hypothesized that they would be the major alarm system in the brain before overt microglia activation. In order to investigate this hypothesis, we induced acute pancreatitis in 8-10week old rats and collected brain tissue, 12 and 24h following pancreatic injury, to measure neuropeptide and cytokine tissue levels. We found significantly higher levels of β-endorphin, orexin and oxytocin in the brain of rats submitted to pancreatic injury, when compared to healthy controls. Interestingly, these differences were not associated with increased local cytokine levels, putting in evidence that neuropeptide release occurred independently of microglia activation and may be a pivotal alarm system to initiate neurologic reactions to distant inflammatory non-infectious aggression.

  8. Effects of microsurgical technique treatment on acknowledge ability,activities of daily living, cortex blood perfusion and neuropeptide levels of brain glioma patients%显微手术对87例脑胶质瘤患者认知、生活能力及血流灌注和神经肽水平的影响

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    苏祖禄; 陈浩皓; 苏海; 张毅

    2014-01-01

    目的:研究显微手术治疗对于脑胶质瘤患者认知、生活能力、皮层血流灌注和脑脊液神经肽类物质水平的影响。方法采用显微手术和传统手术分别治疗87例脑胶质瘤患者,采用长谷川智能量表(HDS)、简易精神状态量表(MMSE)和日常生活能力量表(ADL)评估患者认知、生活能力,并检测患者术后皮层血流灌注情况和脑脊液精氨酸加压素(AVP)、催产素(OT)、β-内啡肽(β-EP)、生长抑素(SS)和神经降压素(NT)的水平。结果显微手术患者的 HDS、MMSE和ADL量表评分均显著优于传统手术,且皮层血流灌注丰富,差异均有统计学意义(P<0.05);脑脊液中5种神经肽类物质水平也高于传统手术患者,差异有统计学意义(P<0.05)。结论显微手术能够改善脑胶质瘤患者认知、生活能力,改善脑血流灌注,恢复脑脊液神经肽水平。%Objective To explore the effects of microsurgical technique treatment on acknowledge ability ,activities of daily liv-ing ,cortex blood perfusion and neuropeptide levels of brain glioma patients .Methods Microsurgical technique treatment and tradi-tional operation were given to 87 brain glioma patients ,respectively .The acknowledge ability and activities of daily living were measured by HDS ,MMSE and ADL ;the cortex blood perfusion were revealed by PET ,and the neuropeptide levels including argi-nine vasopressin ,oxytocin ,β-endorphin ,somatostatin and neurotensin of patients from two different surgical groups were compared . Results As compared with the traditional operation ,the acknowledge ability and activities of daily living of patients from microsur-gical treatment group were significantly improved(P<0 .05) ,the cortex blood perfusion were statistically increased (P<0 .05) and the levels of five kinds of neuropeptide were all profoundly increased (P< 0 .05) .Conclusion Microsurgical technique treatment could

  9. Monkey brain cortex imaging by photoacoustic tomography

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    Yang, Xinmai; Wang, Lihong V.

    2008-01-01

    Photoacoustic tomography (PAT) is applied to image the brain cortex of a monkey through the intact scalp and skull ex vivo. The reconstructed PAT image shows the major blood vessels on the monkey brain cortex. For comparison, the brain cortex is imaged without the scalp, and then imaged again without the scalp and skull. Ultrasound attenuation through the skull is also measured at various incidence angles. This study demonstrates that PAT of the brain cortex is capable of surviving the ultras...

  10. Brain clock driven by neuropeptides and second messengers

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    Miro-Bueno, Jesus; Sosík, Petr

    2014-09-01

    The master circadian pacemaker in mammals is localized in a small portion of the brain called the suprachiasmatic nucleus (SCN). It is unclear how the SCN produces circadian rhythms. A common interpretation is that the SCN produces oscillations through the coupling of genetic oscillators in the neurons. The coupling is effected by a network of neuropeptides and second messengers. This network is crucial for the correct function of the SCN. However, models that study a possible oscillatory behavior of the network itself have received little attention. Here we propose and analyze a model to examine this oscillatory potential. We show that an intercellular oscillator emerges in the SCN as a result of the neuropeptide and second messenger dynamics. We find that this intercellular clock can produce circadian rhythms by itself with and without genetic clocks. We also found that the model is robust to perturbation of parameters and can be entrained by light-dark cycles.

  11. Monkey brain cortex imaging by photoacoustic tomography.

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    Yang, Xinmai; Wang, Lihong V

    2008-01-01

    Photoacoustic tomography (PAT) is applied to image the brain cortex of a monkey through the intact scalp and skull ex vivo. The reconstructed PAT image shows the major blood vessels on the monkey brain cortex. For comparison, the brain cortex is imaged without the scalp, and then imaged again without the scalp and skull. Ultrasound attenuation through the skull is also measured at various incidence angles. This study demonstrates that PAT of the brain cortex is capable of surviving the ultrasound signal attenuation and distortion caused by a relatively thick skull.

  12. Neuropeptide S overcomes short term memory deficit induced by sleep restriction by increasing prefrontal cortex activity.

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    Thomasson, Julien; Canini, Frédéric; Poly-Thomasson, Betty; Trousselard, Marion; Granon, Sylvie; Chauveau, Frédéric

    2017-09-20

    Sleep restriction (SR) impairs short term memory (STM) that might be related to different processes. Neuropeptide S (NPS), an endogenous neuropeptide that improves short term memory, activates arousal and decreases anxiety is likely to counteract the SR-induced impairment of STM. The objective of the present study was to find common cerebral pathways in sleep restriction and NPS action in order to ultimately antagonize SR effect on memory. The STM was assessed using a spontaneous spatial alternation task in a T-maze. C57-Bl/6J male mice were distributed in 4 groups according to treatment (0.1nmol of NPS or vehicle intracerebroventricular injection) and to 20h-SR. Immediately after behavioural testing, regional c-fos immunohistochemistry was performed and used as a neural activation marker for spatial short term memory (prefrontal cortex, dorsal hippocampus) and emotional reactivity (basolateral amygdala and ventral hippocampus). Anxiety-like behaviour was assessed using elevated-plus maze task. Results showed that SR impaired short term memory performance and decreased neuronal activation in cingular cortex.NPS injection overcame SR-induced STM deficits and increased neuronal activation in infralimbic cortex. SR spared anxiety-like behavior in the elevated-plus maze. Neural activation in basolateral nucleus of amygdala and ventral hippocampus were not changed after SR.In conclusion, the present study shows that NPS overcomes SR-induced STM deficits by increasing prefrontal cortex activation independently of anxiety-like behaviour. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Influence of Ganoderma lucidum spores on the levels of neuropeptide Y and somatostatin in brains of seizure rats

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    Kongli Zhu; Ming Lu; Shuqiu Wang; Shiling Zhang; Dixiang Sun

    2008-01-01

    BACKGROUND: Previous research has revealed that somatostatin can induce epilepsy, and that the levels of neuropeptide Y may increase and become more active in brain areas with epileptic seizures.OBJECTIVE: To observe the effect of Ganoderma lucidum spore powder on the neuropeptide Y and somatostatin content in the cerebral cortex and hippocampal regions of seizure rats induced by pentylenetetrazol (PTZ). Furthermore, to verify any effect of Ganoderma lucidum spore powder on inhibition of epileptic seizures.DESIGN, TIME AND SETTING: A randomized group animal study was performed in August 2007 in the School of Basic Medical Sciences, Jiamusi University (Jiamusi, Heilongjiang, China).MATERIALS: Thirty healthy, male, Wistar rats, aged 12 weeks and weighing 180-220g, were taken as the experimental animals. PTZ (Sigma Company, United States) was used to induce epilepsy. Ganoderma lucidum spores (Leyss, ex Fr variety) were purchased from Jiamusi City Wild Growing Case of the Ganoderma Lucidum (China). Rabbit anti-somatostatin antibodies and secondary antibodies were purchased from Wuhan Boster Company (China). Neuropeptide Y radioimmunoassay kit was purchased from Beijing Furui Biotechnology Company (China).METHODS: Thirty rats were randomly divided into three groups: a control group, an epilepsy model group and a Ganoderma lucidum spore-treated group. Each group contained 10 animals. Rats in the epilepsy model group were treated with intraperitoneal injections of PTZ and gastric perfusion of physiologic saline, In the Ganoderma lucidum spore-treated group, intraperitoneal injection of PTZ and gastric perfusion of Ganoderma lucidum spore powder were administered. The blank control group was only administered with the physiological saline by intraperitoneal injection and gastric perfusion.MAIN OUTCOME MEASURES: Immunohistochemical staining and radioimmunoassay methods were used to observe the changes of somatostatin and neuropeptide Y content in brain tissue of epileptic

  14. Anti-epileptic effects of neuropeptide Y gene transfection into the rat brain

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    Changzheng Dong; Wenqing Zhao; Wenling Li; Peiyuan Lv; Xiufang Dong

    2013-01-01

    Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carrying the neuropeptide Y gene was transfected into brain tissue of rats with kainic acid-induced epilepsy through stereotactic methods. Following these transfections, we verified overexpression of the neuropeptide Y gene in the epileptic brain. Electroencephalograms showed that seizure severity was significantly inhibited and seizure latency was significantly prolonged up to 4 weeks after gene transfection. Moreover, quantitative fluorescent PCR and western blot assays revealed that the mRNA and protein expression of the N-methyl-D-aspartate receptor subunits NR1, NR2A, and NR2B was inhibited in the hippocampus of epileptic rats. These findings indicate that neuropeptide Y may inhibit seizures via down-regulation of the functional expression of N-methyl-D-aspartate receptors.

  15. Neuropeptide Y receptor binding sites in rat brain: differential autoradiographic localizations with sup 125 I-peptide YY and sup 125 I-neuropeptide Y imply receptor heterogeneity

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    Lynch, D.R.; Walker, M.W.; Miller, R.J.; Snyder, S.H. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1989-08-01

    Neuropeptide Y (NPY) receptor binding sites have been localized in the rat brain by in vitro autoradiography using picomolar concentrations of both 125I-NPY and 125I-peptide YY (PYY) and new evidence provided for differentially localized receptor subtypes. Equilibrium binding studies using membranes indicate that rat brain contains a small population of high-affinity binding sites and a large population of moderate-affinity binding sites. 125I-PYY (10 pM) is selective for high-affinity binding sites (KD = 23 pM), whereas 10 pM 125I-NPY labels both high- and moderate-affinity sites (KD = 54 pM and 920 pM). The peptide specificity and affinity of these ligands in autoradiographic experiments match those seen in homogenates. Binding sites for 125I-PYY are most concentrated in the lateral septum, stratum oriens, and radiatum of the hippocampus, amygdala, piriform cortex, entorhinal cortex, several thalamic nuclei, including the reuniens and lateral posterior nuclei, and substantia nigra, pars compacta, and pars lateralis. In the brain stem, 125I-PYY sites are densest in a variety of nuclei on the floor of the fourth ventricle, including the pontine central grey, the supragenual nucleus, and the area postrema. 125I-NPY binding sites are found in similar areas, but relative levels of NPY binding and PYY binding differ regionally, suggesting differences in sites labeled by the two ligands. These receptor localizations resemble the distribution of endogenous NPY in some areas, but others, such as the hypothalamus, contain NPY immunoreactivity but few binding sites.

  16. Immunohistochemical localization of neuropeptide FF-like in the brain of the turtle: relation to catecholaminergic structures.

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    Muñoz, M; Smeets, W J A J; López, J M; Moreno, N; Morona, R; Domínguez, L; González, A

    2008-03-18

    A previous study in the lizard Gekko gecko has revealed that neuropeptide FF (NPFF, a neuropeptide involved in nociception, cardiovascular regulation, and endocrine function) is widely distributed throughout the brain and spinal cord. Although the distribution of NPFF immunoreactivity shares many features with that found in other vertebrates, it was noted that Gekko shared more features with anamniotes in terms of number of cell groups, more elaborate networks of fibers, and lack of colocalization with catecholamines, than with mammals. To assess the primitive or derived character of these features, NPFF and tyrosine hydroxylase (TH) antibodies have been applied to the brain and spinal cord of the turtle, Pseudemys scripta elegans, which belongs to a different radiation of reptiles. As in Gekko, major NPFF-ir cell groups were found in the diagonal band nucleus of Broca and in the hypothalamus, whereas additional cells were identified in the anterior olfactory nucleus, lateral and dorsal cortices, dorsal ventricular ridge, and the intergeniculate leaflet formation. Notable differences are the presence of NPFF-ir cells in the medial cortex and striatum of Pseudemys, which are lacking in Gekko. On the other hand, no NPFF-ir cells could be detected in the septal region and dorsal horn of the spinal cord in Pseudemys. Double staining with NPFF and TH antibodies revealed an intimate relationship between NPFF-ir and TH-ir structures but colocalization could not be established. In conclusion, the distribution of NPFF in the brain of Pseudemys has corroborated previous results in Gekko, but also revealed some notable species differences.

  17. MALDI imaging analysis of neuropeptides in the Africanized honeybee (Apis mellifera) brain: effect of ontogeny.

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    Pratavieira, Marcel; da Silva Menegasso, Anally Ribeiro; Garcia, Ana Maria Caviquioli; Dos Santos, Diego Simões; Gomes, Paulo Cesar; Malaspina, Osmar; Palma, Mario Sergio

    2014-06-01

    The occurrence and spatial distribution of the neuropeptides AmTRP-5 and AST-1 in the honeybee brain were monitored via MALDI spectral imaging according to the ontogeny of Africanized Apis mellifera. The levels of these peptides increased in the brains of 0-15 day old honeybees, and this increase was accompanied by an increase in the number of in-hive activities performed by the nurse bees, followed by a decrease in the period from 15 to 25 days of age, in which the workers began to perform activities outside the nest (guarding and foraging). The results obtained in the present investigation suggest that AmTRP-5 acts in the upper region of both pedunculi of young workers, possibly regulating the cell cleaning and brood capping activities. Meanwhile, the localized occurrence of AmTRP-5 and AST-1 in the antennal lobes, subesophageal ganglion, upper region of the medulla, both lobula, and α- and β-lobes of both brain hemispheres in 20 to 25 day old workers suggest that the action of both neuropeptides in these regions may be related to their localized actions in these regions, regulating foraging and guarding activities. Thus, these neuropeptides appear to have some functions in the honeybee brain that are specifically related to the age-related division of labor.

  18. Neuropeptide S facilitates mice olfactory function through activation of cognate receptor-expressing neurons in the olfactory cortex.

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    Yu-Feng Shao

    Full Text Available Neuropeptide S (NPS is a newly identified neuromodulator located in the brainstem and regulates various biological functions by selectively activating the NPS receptors (NPSR. High level expression of NPSR mRNA in the olfactory cortex suggests that NPS-NPSR system might be involved in the regulation of olfactory function. The present study was undertaken to investigate the effects of intracerebroventricular (i.c.v. injection of NPS or co-injection of NPSR antagonist on the olfactory behaviors, food intake, and c-Fos expression in olfactory cortex in mice. In addition, dual-immunofluorescence was employed to identify NPS-induced Fos immunereactive (-ir neurons that also bear NPSR. NPS (0.1-1 nmol i.c.v. injection significantly reduced the latency to find the buried food, and increased olfactory differentiation of different odors and the total sniffing time spent in olfactory habituation/dishabituation tasks. NPS facilitated olfactory ability most at the dose of 0.5 nmol, which could be blocked by co-injection of 40 nmol NPSR antagonist [D-Val(5]NPS. NPS administration dose-dependently inhibited food intake in fasted mice. Ex-vivo c-Fos and NPSR immunohistochemistry in the olfactory cortex revealed that, as compared with vehicle-treated mice, NPS markedly enhanced c-Fos expression in the anterior olfactory nucleus (AON, piriform cortex (Pir, ventral tenia tecta (VTT, the anterior cortical amygdaloid nucleus (ACo and lateral entorhinal cortex (LEnt. The percentage of Fos-ir neurons that also express NPSR were 88.5% and 98.1% in the AON and Pir, respectively. The present findings demonstrated that NPS, via selective activation of the neurons bearing NPSR in the olfactory cortex, facilitates olfactory function in mice.

  19. Differential regulation of Neuropeptide Y (NPY in the amygdala and prefrontal cortex during recovery from chronic variable stress (CVS

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    Jennifer Lynne McGuire

    2011-09-01

    Full Text Available Accumulating evidence from clinical studies and pre-clinical animal models supports a role for neuropeptide Y (NPY in adaptive emotional response following stress. The long-term impact of stress, particularly chronic stress, on availability and function of resilience factors such as NPY may be critical to understanding the etiology of stress-related psychopathology. In these studies, we examined expression of NPY during recovery from a chronic variable stress (CVS model of repetitive trauma in rats. Due to the importance of amygdala and prefrontal cortex in regulating emotional responses, we predicted chronic changes in NPY expression could contribute to persistent behavioral deficits seen in this model. Consistent with the hypothesis, ELISA for NPY peptide identified a significant reduction in NPY at the delayed (7 days recovery timepoint. Interestingly, a significant increase in prefrontal NPY was observed at the same recovery timepoint.. The mRNA expression for NPY was not changed in the amygdala or PFC, although there was a modest but not statistically significant increase in NPY mRNA at the delayed recovery timepoint in the prefrontal cortex. The observed changes in NPY expression are consistent with maladaptive coping and enhanced emotionality, due to the nature of NPY signaling within these respective regions, and the nature of reciprocal connections between amygdala and prefrontal cortex.

  20. Profiling of diet-induced neuropeptide changes in rat brain by quantitative mass spectrometry

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    Frese, C.; Boender, A.J.; Mohammed, S.; Heck, A.J.R.; Adan, R.A.H.; Altelaar, A.F.M.

    2013-01-01

    Neuropeptides are intercellular signal transmitters that play key roles in modulation of many behavioral and physiological processes. Neuropeptide signaling in several nuclei in the hypothalamus contributes to the control of food intake. Additionally, food intake regulation involves neuropeptide

  1. Altered expression of neuropeptides in the primary somatosensory cortex of the Down syndrome model Ts65Dn.

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    Hernández, Samuel; Gilabert-Juan, Javier; Blasco-Ibáñez, José Miguel; Crespo, Carlos; Nácher, Juan; Varea, Emilio

    2012-02-01

    Down syndrome is the most common genetic disorder associated with mental retardation. Subjects and mice models for Down syndrome (such as Ts65Dn) show defects in the formation of neuronal networks in both the hippocampus and the cerebral cortex. The principal neurons display alterations in the morphology, density and distribution of dendritic spines in the cortex as well as in the hippocampus. Several evidences point to the possibility that the atrophy observed in principal neurons could be mediated by changes in their inhibitory inputs and, in fact, an imbalance between excitation and inhibition has been observed in Ts65Dn mice in these regions, which are crucial for learning and information processing. These animals have an increased density of interneurons in the primary somatosensory cortex, especially of those expressing calretinin and calbindin D-28k. Here, we have analysed the expression and distribution of several neuropeptides in the primary somatosensory cortex of Ts65Dn mice in order to investigate whether these subpopulations of interneurons are affected. We have observed an increase in the total density of somatostatin expressing interneurons and of those expressing VIP in layer IV in Ts65Dn mice. The typology of the somatostatin and VIP interneurons was unaltered as attested by the pattern of co-expression with other markers. Somatostatin immunoreactive neurons co-express mainly D-28k calbindin and VIP expressing interneurons maintain its pattern of co-expression with calcium binding proteins. These alterations, in case they were also present in subjects with Down syndrome, could be related to their impairment in cognitive profile and could be involved in the neurological defects observed in this disorder.

  2. Effects of acute heat stress on gene expression of brain-gut neuropeptides in broiler chickens.

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    Lei, L; Hepeng, L; Xianlei, L; Hongchao, J; Hai, L; Sheikhahmadi, A; Yufeng, W; Zhigang, S

    2013-11-01

    Heat stress-induced reduction in feed intake is an annoyance of the poultry industry. Feed intake is regulated by complex mechanisms in which brain-gut neuropeptides are involved, but the changes in such neuropeptides in broiler chickens during heat exposure remain unclear. In this study, we investigated the effects of acute heat stress (35°C, 6 h, and 65% relative humidity) on the gene expression of appetite-regulating peptides in the hypothalamus and gastrointestinal tract of broiler chickens at 42 d of age. The hypothalamic mRNA levels of neuropeptide Y, agouti-related peptide, pro-opiomelanocortin, cocaine- and amphetamine-regulated transcript, corticotropin-releasing hormone, melanocortin 4 receptor, melanin-concentrating hormone, prepro-orexin, cholecystokinin (CCK), and ghrelin did not significantly change (P>0.05) in the heat-exposed broiler chickens. However, the mRNA levels of ghrelin in the glandular stomach, duodenum, and jejunum significantly increased and the mRNA level of CCK in the duodenum significantly decreased. The results indicate that acute heat stress had no effect on the gene expression of central appetite-regulating peptides under current experimental conditions; however, some gastrointestinal tract peptides (e.g., ghrelin and CCK) might play a role in the regulation of appetite in acute heat-exposed broiler chickens. Furthermore, ghrelin in the glandular stomach, duodenum, and jejunum might be the main regulative target of acute heat stress induced anorexia.

  3. Neuropeptides, Microbiota, and Behavior.

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    Holzer, P

    2016-01-01

    The gut microbiota and the brain interact with each other through multiple bidirectional signaling pathways in which neuropeptides and neuroactive peptide messengers play potentially important mediator roles. Currently, six particular modes of a neuropeptide link are emerging. (i) Neuropeptides and neurotransmitters contribute to the mutual microbiota-host interaction. (ii) The synthesis of neuroactive peptides is influenced by microbial control of the availability of amino acids. (iii) The activity of neuropeptides is tempered by microbiota-dependent autoantibodies. (iv) Peptide signaling between periphery and brain is modified by a regulatory action of the gut microbiota on the blood-brain barrier. (v) Within the brain, gut hormones released under the influence of the gut microbiota turn into neuropeptides that regulate multiple aspects of brain activity. (vi) Cerebral neuropeptides participate in the molecular, behavioral, and autonomic alterations which the brain undergoes in response to signals from the gut microbiota. © 2016 Elsevier Inc. All rights reserved.

  4. Molecular fingerprint of neuropeptide S-producing neurons in the mouse brain

    DEFF Research Database (Denmark)

    Liu, Xiaobin; Zeng, Joanne; Zhou, Anni

    2011-01-01

    Neuropeptide S (NPS) has been associated with a number of complex brain functions, including anxiety-like behaviors, arousal, sleep-wakefulness regulation, drug-seeking behaviors, and learning and memory. In order to better understand how NPS influences these functions in a neuronal network context....../EGFP-transgenic mice show anatomically correct and overlapping expression of both NPS and EGFP. A total number of ~500 NPS/EGFP-positive neurons are present in the mouse brain, located in the pericoerulear region and the Kölliker-Fuse nucleus. NPS and transgene expression is first detectable around E14, indicating...... network of orexin/hypocretin neuronal projections contacting pericoerulear NPS-producing neurons was observed by immunostaining. Expression of a distinct repertoire of metabotropic and ionotropic receptor genes was identified in both NPS neuronal clusters that will allow for detailed investigations...

  5. Molecular fingerprint of neuropeptide S-producing neurons in the mouse brain

    DEFF Research Database (Denmark)

    Liu, Xiaobin; Zeng, Joanne; Zhou, Anni

    2011-01-01

    Neuropeptide S (NPS) has been associated with a number of complex brain functions, including anxiety-like behaviors, arousal, sleep-wakefulness regulation, drug-seeking behaviors, and learning and memory. In order to better understand how NPS influences these functions in a neuronal network context....../EGFP-transgenic mice show anatomically correct and overlapping expression of both NPS and EGFP. A total number of ∼500 NPS/EGFP-positive neurons are present in the mouse brain, located in the pericoerulear region and the Kölliker-Fuse nucleus. NPS and transgene expression is first detectable around E14, indicating...... network of orexin/hypocretin neuronal projections contacting pericoerulear NPS-producing neurons was observed by immunostaining. Expression of a distinct repertoire of metabotropic and ionotropic receptor genes was identified in both NPS neuronal clusters that will allow for detailed investigations...

  6. Three-dimensional microtomographic imaging of human brain cortex

    CERN Document Server

    Mizutania, Ryuta; Uesugi, Kentaro; Ohyama, Masami; Takekoshi, Susumu; Osamura, R Yoshiyuki; Suzuki, Yoshio

    2016-01-01

    This paper describes an x-ray microtomographic technique for imaging the three-dimensional structure of the human cerebral cortex. Neurons in the brain constitute a neural circuit as a three-dimensional network. The brain tissue is composed of light elements that give little contrast in a hard x-ray transmission image. The contrast was enhanced by staining neural cells with metal compounds. The obtained structure revealed the microarchitecture of the gray and white matter regions of the frontal cortex, which is responsible for the higher brain functions.

  7. Metabolic stress responses in Drosophila are modulated by brain neurosecretory cells that produce multiple neuropeptides.

    Directory of Open Access Journals (Sweden)

    Lily Kahsai

    Full Text Available In Drosophila, neurosecretory cells that release peptide hormones play a prominent role in the regulation of development, growth, metabolism, and reproduction. Several types of peptidergic neurosecretory cells have been identified in the brain of Drosophila with release sites in the corpora cardiaca and anterior aorta. We show here that in adult flies the products of three neuropeptide precursors are colocalized in five pairs of large protocerebral neurosecretory cells in two clusters (designated ipc-1 and ipc-2a: Drosophila tachykinin (DTK, short neuropeptide F (sNPF and ion transport peptide (ITP. These peptides were detected by immunocytochemistry in combination with GFP expression driven by the enhancer trap Gal4 lines c929 and Kurs-6, both of which are expressed in ipc-1 and 2a cells. This mix of colocalized peptides with seemingly unrelated functions is intriguing and prompted us to initiate analysis of the function of the ten neurosecretory cells. We investigated the role of peptide signaling from large ipc-1 and 2a cells in stress responses by monitoring the effect of starvation and desiccation in flies with levels of DTK or sNPF diminished by RNA interference. Using the Gal4-UAS system we targeted the peptide knockdown specifically to ipc-1 and 2a cells with the c929 and Kurs-6 drivers. Flies with reduced DTK or sNPF levels in these cells displayed decreased survival time at desiccation and starvation, as well as increased water loss at desiccation. Our data suggest that homeostasis during metabolic stress requires intact peptide signaling by ipc-1 and 2a neurosecretory cells.

  8. Metabolic Stress Responses in Drosophila Are Modulated by Brain Neurosecretory Cells That Produce Multiple Neuropeptides

    Science.gov (United States)

    Kahsai, Lily; Kapan, Neval; Dircksen, Heinrich; Winther, Åsa M. E.; Nässel, Dick R.

    2010-01-01

    In Drosophila, neurosecretory cells that release peptide hormones play a prominent role in the regulation of development, growth, metabolism, and reproduction. Several types of peptidergic neurosecretory cells have been identified in the brain of Drosophila with release sites in the corpora cardiaca and anterior aorta. We show here that in adult flies the products of three neuropeptide precursors are colocalized in five pairs of large protocerebral neurosecretory cells in two clusters (designated ipc-1 and ipc-2a): Drosophila tachykinin (DTK), short neuropeptide F (sNPF) and ion transport peptide (ITP). These peptides were detected by immunocytochemistry in combination with GFP expression driven by the enhancer trap Gal4 lines c929 and Kurs-6, both of which are expressed in ipc-1 and 2a cells. This mix of colocalized peptides with seemingly unrelated functions is intriguing and prompted us to initiate analysis of the function of the ten neurosecretory cells. We investigated the role of peptide signaling from large ipc-1 and 2a cells in stress responses by monitoring the effect of starvation and desiccation in flies with levels of DTK or sNPF diminished by RNA interference. Using the Gal4-UAS system we targeted the peptide knockdown specifically to ipc-1 and 2a cells with the c929 and Kurs-6 drivers. Flies with reduced DTK or sNPF levels in these cells displayed decreased survival time at desiccation and starvation, as well as increased water loss at desiccation. Our data suggest that homeostasis during metabolic stress requires intact peptide signaling by ipc-1 and 2a neurosecretory cells. PMID:20628603

  9. Mescaline-induced changes of brain-cortex ribosomes. Effect of mescaline on the stability of brain-cortex ribosomes.

    Science.gov (United States)

    Datta, R K; Ghosh, J J

    1970-05-01

    1. During the action of mescaline sulphate on goat brain-cortex slices the ribosomal particles become susceptible to breakdown, releasing protein, RNA, acidsoluble nucleotides and ninhydrin-positive materials, resulting in loss of ribosomal enzyme activities. 2. Ribosomes of the mescaline-treated cortex slices undergo rapid degradation in the presence of trypsin and ribonuclease. 3. Mescaline does not alter the chemical and nucleotide compositions or the u.v.-absorption characteristics of ribosomal particles, however.

  10. Immunohistochemical evidence for the presence of a Vasoactive Intestinal Peptide, Neuropeptide Y, and Substance P, in rat adrenal cortex after acute heat stress

    Directory of Open Access Journals (Sweden)

    Petrović-Kosanović Dragana

    2013-01-01

    Full Text Available Immunohistochemistry revealed the presence of Vasoactive Intestinal Peptide (VIP, Neuropeptide Y (NPY, and the absence of Substance P (SP immunoreactivity in the rat adrenal cortex. VIP- and NPY-immunoreactivity were detected in nerve fibers around the small blood vessels projecting into the capsule and cortical zones surrounding blood vessels and cortical cells. After acute heat stress, VIP- and NPY-immunoreactivities in the nerve fibers were reduced, probably as a result of the release of these peptides. [Projekat Ministarstva nauke Republike Srbije, br. 173023

  11. Multifaces of neuropeptide Y in the brain--neuroprotection, neurogenesis and neuroinflammation.

    Science.gov (United States)

    Malva, J O; Xapelli, S; Baptista, S; Valero, J; Agasse, F; Ferreira, R; Silva, A P

    2012-12-01

    Neuropeptide Y (NPY) has been implicated in the modulation of important features of neuronal physiology, including calcium homeostasis, neurotransmitter release and excitability. Moreover, NPY has been involved as an important modulator of hippocampal and thalamic circuits, receiving particular attention as an endogenous antiepileptic peptide and as a potential master regulator of feeding behavior. NPY not only inhibits excessive glutamate release (decreasing circuitry hyperexcitability) but also protects neurons from excitotoxic cell death. Furthermore, NPY has been involved in the modulation of the dynamics of dentate gyrus and subventricular zone neural stem cell niches. In both regions, NPY is part of the chemical resource of the neurogenic niche and acts through NPY Y1 receptors to promote neuronal differentiation. Interestingly, NPY is also considered a neuroimmune messenger. In this review, we highlight recent evidences concerning paracrine/autocrine actions of NPY involved in neuroprotection, neurogenesis and neuroinflammation. In summary, the three faces of NPY, discussed in the present review, may contribute to better understand the dynamics and cell fate decision in the brain parenchyma and in restricted areas of neurogenic niches, in health and disease.

  12. Mescaline-induced changes of brain-cortex ribosomes. Effect of mescaline on the hydrogen-bonded structure of ribonucleic acid of brain-cortex ribosomes.

    Science.gov (United States)

    Datta, R K; Ghosh, J J

    1970-05-01

    1. The action of mescaline sulphate on the hydrogen-bonded structure of the RNA constituent of ribosomes of goat brain-cortex slices was studied by using the hyperchromic effect of heating and formaldehyde reaction. 2. The ribosomal total RNA species of the mescaline-treated brain-cortex slices have a smaller proportion of hydrogen-bonded structure than the ribosomal RNA species of the untreated brain-cortex slices. 3. Mescaline also appears to have affected this lowering of hydrogen-bonded structure of the ribosomal 28S RNA of brain-cortex tissue.

  13. The relationship between brain cortical activity and brain oxygenation in the prefrontal cortex during hypergravity exposure.

    Science.gov (United States)

    Smith, Craig; Goswami, Nandu; Robinson, Ryan; von der Wiesche, Melanie; Schneider, Stefan

    2013-04-01

    Artificial gravity has been proposed as a method to counteract the physiological deconditioning of long-duration spaceflight; however, the effects of hypergravity on the central nervous system has had little study. The study aims to investigate whether there is a relationship between prefrontal cortex brain activity and prefrontal cortex oxygenation during exposure to hypergravity. Twelve healthy participants were selected to undergo hypergravity exposure aboard a short-arm human centrifuge. Participants were exposed to hypergravity in the +Gz axis, starting from 0.6 +Gz for women, and 0.8 +Gz for men, and gradually increasing by 0.1 +Gz until the participant showed signs of syncope. Brain cortical activity was measured using electroencephalography (EEG) and localized to the prefrontal cortex using standard low-resolution brain electromagnetic tomography (LORETA). Prefrontal cortex oxygenation was measured using near-infrared spectroscopy (NIRS). A significant increase in prefrontal cortex activity (P Prefrontal cortex oxygenation was significantly decreased during hypergravity exposure, with a decrease in oxyhemoglobin levels (P prefrontal cortex activity and oxy-/deoxyhemoglobin. It is concluded that the increase in prefrontal cortex activity observed during hypergravity was most likely not the result of increased +Gz values resulting in a decreased oxygenation produced through hypergravity exposure. No significant relationship between prefrontal cortex activity and oxygenation measured by NIRS concludes that brain activity during exposure to hypergravity may be difficult to measure using NIRS. Instead, the increase in prefrontal cortex activity might be attributable to psychological stress, which could pose a problem for the use of a short-arm human centrifuge as a countermeasure.

  14. Calretinin and Neuropeptide Y interneurons are differentially altered in the motor cortex of the SOD1G93A mouse model of ALS

    Science.gov (United States)

    Clark, Rosemary M.; Blizzard, Catherine A.; Young, Kaylene M.; King, Anna E.; Dickson, Tracey C.

    2017-01-01

    Increasing evidence indicates an excitatory/inhibitory imbalance may have a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Impaired inhibitory circuitry is consistently reported in the motor cortex of both familial and sporadic patients, closely associated with cortical hyperexcitability and ALS onset. Inhibitory network dysfunction is presumably mediated by intra-cortical inhibitory interneurons, however, the exact cell types responsible are yet to be identified. In this study we demonstrate dynamic changes in the number of calretinin- (CR) and neuropeptide Y-expressing (NPY) interneurons in the motor cortex of the familial hSOD1G93A ALS mouse model, suggesting their potential involvement in motor neuron circuitry defects. We show that the density of NPY-populations is significantly decreased by ~17% at symptom onset (8 weeks), and by end-stage disease (20 weeks) is significantly increased by ~30%. Conversely, the density of CR-populations is progressively reduced during later symptomatic stages (~31%) to end-stage (~36%), while CR-expressing interneurons also show alteration of neurite branching patterns at symptom onset. We conclude that a differential capacity for interneurons exists in the ALS motor cortex, which may not be a static phenomenon, but involves early dynamic changes throughout disease, implicating specific inhibitory circuitry. PMID:28294153

  15. Sensory cortex underpinnings of traumatic brain injury deficits.

    Directory of Open Access Journals (Sweden)

    Dasuni S Alwis

    Full Text Available Traumatic brain injury (TBI can result in persistent sensorimotor and cognitive deficits including long-term altered sensory processing. The few animal models of sensory cortical processing effects of TBI have been limited to examination of effects immediately after TBI and only in some layers of cortex. We have now used the rat whisker tactile system and the cortex processing whisker-derived input to provide a highly detailed description of TBI-induced long-term changes in neuronal responses across the entire columnar network in primary sensory cortex. Brain injury (n=19 was induced using an impact acceleration method and sham controls received surgery only (n=15. Animals were tested in a range of sensorimotor behaviour tasks prior to and up to 6 weeks post-injury when there were still significant sensorimotor behaviour deficits. At 8-10 weeks post-trauma, in terminal experiments, extracellular recordings were obtained from barrel cortex neurons in response to whisker motion, including motion that mimicked whisker motion observed in awake animals undertaking different tasks. In cortex, there were lamina-specific neuronal response alterations that appeared to reflect local circuit changes. Hyper-excitation was found only in supragranular layers involved in intra-areal processing and long-range integration, and only for stimulation with complex, naturalistic whisker motion patterns and not for stimulation with simple trapezoidal whisker motion. Thus TBI induces long-term directional changes in integrative sensory cortical layers that depend on the complexity of the incoming sensory information. The nature of these changes allow predictions as to what types of sensory processes may be affected in TBI and contribute to post-trauma sensorimotor deficits.

  16. How to contribute to the progress of neuroendocrinology: New insights from discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions.

    Science.gov (United States)

    Tsutsui, Kazuyoshi

    2016-02-01

    Obtaining new insights by discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions is essential for the progress of neuroendocrinology. At the beginning of 1970s, gonadotropin-releasing hormone (GnRH) was discovered in mammals. Since then, it was generally accepted that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in vertebrates. In 2000, however, gonadotropin-inhibitory hormone (GnIH), a novel hypothalamic neuropeptide that actively inhibits gonadotropin release, was discovered in quail. The follow-up studies demonstrated that GnIH acts as a new key player for regulation of reproduction across vertebrates. It now appears that GnIH acts on the pituitary and the brain to serve a number of behavioral and physiological functions. On the other hand, a new concept has been established that the brain synthesizes steroids, called neurosteroids. The formation of neurosteroids in the brain was originally demonstrated in mammals and subsequently in other vertebrates. Recently, 7α-hydroxypregnenolone was discovered as a novel bioactive neurosteroid inducing locomotor behavior of vertebrates, indicating that neurosteroidogenesis in the brain is still incompletely elucidated in vertebrates. At the beginning of 2010s, it was further found that the pineal gland actively produces neurosteroids. Pineal neurosteroids act on the brain to regulate locomotor rhythms and neuronal survival. Furthermore, the interaction of neuropeptides and neurosteroids is becoming clear. GnIH decreases aggressive behavior by regulating neuroestrogen synthesis in the brain. This review summarizes these new insights by discovering novel neuropeptides and neurosteroids in the field of neuroendocrinology.

  17. Overexpression of neuropeptide Y induced by brain-derived neurotrophic factor in the rat hippocampus is long lasting.

    Science.gov (United States)

    Reibel, S; Vivien-Roels, B; Lê, B T; Larmet, Y; Carnahan, J; Marescaux, C; Depaulis, A

    2000-02-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in hippocampal neuroplasticity. In particular, BDNF upregulation in the hippocampus by epileptic seizures suggests its involvement in the neuronal rearrangements accompanying epileptogenesis. We have shown previously that chronic infusion of BDNF in the hippocampus induces a long-term delay in hippocampal kindling progression. Although BDNF has been shown to enhance the excitability of this structure upon acute application, long-term transcriptional regulations leading to increased inhibition within the hippocampus may account for its suppressive effects on epileptogenesis. Therefore, the long-term consequences of a 7-day chronic intrahippocampal infusion of BDNF (12 microg/day) were investigated up to 2 weeks after the end of the infusion, on the expression of neurotransmitters contained in inhibitory hippocampal interneurons and which display anti-epileptic properties. Our results show that BDNF does not modify levels of immunostaining for glutamic acid decarboxylase, the rate-limiting enzyme for gamma-aminobutyric acid (GABA) synthesis, and somatostatin. Conversely, BDNF induces a long-lasting increase of neuropeptide Y (NPY) in the hippocampus, measured by immunohistochemistry and radioimmunoassay, outlasting the end of the infusion by at least 7 days. The distribution of BDNF-induced neuropeptide Y immunoreactivity is similar to the pattern observed in animals submitted to hippocampal kindling, with the exception of mossy fibres which only become immunoreactive following seizure activity. The enduring increase of neuropeptide Y expression induced by BDNF in the hippocampus suggests that this neurotrophin can trigger long-term genomic effects, which may contribute to the neuroplasticity of this structure, in particular during epileptogenesis.

  18. Mescaline-induced changes of brain-cortex ribosomes. Role of sperimidine in counteracting the destabilizing effect of mescaline of brain-cortex ribosomes.

    Science.gov (United States)

    Datta, R K; Antopol, W; Ghosh, J J

    1971-11-01

    1. The effect of spermidine on the mescaline-induced changes of brain-cortex ribosomes was studied by adding spermidine during the treatment of goat brain-cortex slices with mescaline. 2. Mescaline treatment of brain-cortex slices removed a portion of the endogenous spermidine from ribosomes and this removal was significantly prevented when spermidine was present during mescaline treatment. 3. Spermidine present during mescaline treatment of brain-cortex slices counteracted, to some extent, the destabilizing effect of mescaline on ribosomes with respect to heat denaturation. 4. Mescaline treatment of brain-cortex slices made ribosomes more susceptible to breakdown, releasing protein and RNA, and resulting in loss of ribosomal enzymic activities. However, spermidine present during mescaline treatment counteracted moderately the mescaline-induced ribosomal susceptibility to breakdown and ribosomal loss of enzymic activities. 5. Ribosomes of mescaline-treated cortex slices were rapidly degraded by ribonuclease and trypsin. However, if spermidine was present during mescaline treatment of brain-cortex slices the rates of degradation diminished.

  19. Neuropeptides in epilepsy.

    Science.gov (United States)

    Kovac, Stjepana; Walker, Matthew C

    2013-12-01

    Neuropeptides play an important role in modulating seizures and epilepsy. Unlike neurotransmitters which operate on a millisecond time-scale, neuropeptides have longer half lives; this leads to modulation of neuronal and network activity over prolonged periods, so contributing to setting the seizure threshold. Most neuropeptides are stored in large dense vesicles and co-localize with inhibitory interneurons. They are released upon high frequency stimulation making them attractive targets for modulation of seizures, during which high frequency discharges occur. Numerous neuropeptides have been implicated in epilepsy; one, ACTH, is already used in clinical practice to suppress seizures. Here, we concentrate on neuropeptides that have a direct effect on seizures, and for which therapeutic interventions are being developed. We have thus reviewed the abundant reports that support a role for neuropeptide Y (NPY), galanin, ghrelin, somatostatin and dynorphin in suppressing seizures and epileptogenesis, and for tachykinins having pro-epileptic effects. Most in vitro and in vivo studies are performed in hippocampal tissue in which receptor expression is usually high, making translation to other brain areas less clear. We highlight recent therapeutic strategies to treat epilepsy with neuropeptides, which are based on viral vector technology, and outline how such interventions need to be refined in order to address human disease.

  20. Effects of prolonged ethanol vapor exposure on forced swim behavior, and neuropeptide Y and corticotropin-releasing factor levels in rat brains.

    Science.gov (United States)

    Walker, Brendan M; Drimmer, David A; Walker, Jennifer L; Liu, Tianmin; Mathé, Aleksander A; Ehlers, Cindy L

    2010-09-01

    Depressive symptoms in alcohol-dependent individuals are well-recognized and clinically relevant phenomena. The etiology has not been elucidated although it is clear that the depressive symptoms may be alcohol independent or alcohol induced. To contribute to the understanding of the neurobiology of chronic ethanol use, we investigated the effects of chronic intermittent ethanol vapor exposure on behaviors in the forced swim test (FST) and neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) levels in specific brain regions. Adult male Wistar rats were subjected to intermittent ethanol vapor (14 h on/10 h off) or air exposure for 2 weeks and were then tested at three time points corresponding to acute withdrawal (8-12 h into withdrawal) and protracted withdrawal (30 and 60 days of withdrawal) in the FST. The behaviors that were measured in the five-min FST consisted of latency to immobility, swim time, immobility time, and climbing time. The FST results showed that the vapor-exposed animals displayed depressive-like behaviors; for instance, decreased latency to immobility in acute withdrawal and decreased latency to immobility, decreased swim time and increased immobility time in protracted withdrawal, with differences between air- and vapor-exposed animals becoming more pronounced over the 60-day withdrawal period. NPY levels in the frontal cortex of the vapor-exposed animals were decreased compared with the control animals, and CRF levels in the amygdala were correlated with increased immobility time. Thus, extended ethanol vapor exposure produced long-lasting changes in FST behavior and NPY levels in the brain.

  1. Effects of Prolonged Ethanol Vapor Exposure on Forced Swim Behavior, and Neuropeptide Y and Corticotropin Releasing Factor Levels in Rat Brains

    Science.gov (United States)

    Walker, Brendan M.; Drimmer, David A.; Walker, Jennifer L.; Liu, Tianmin; Mathé, Aleksander A.; Ehlers, Cindy L.

    2010-01-01

    Depressive symptoms in alcohol-dependent individuals are well recognized and clinically relevant phenomena. The etiology has not been elucidated although it is clear that the depressive symptoms may be alcohol independent or alcohol-induced. In order to contribute to the understanding of the neurobiology of chronic ethanol use, we investigated the effects of chronic intermittent ethanol vapor exposure on behaviors in the forced swim test (FST) and neuropeptide Y (NPY) and corticotropin releasing factor (CRF) levels in specific brain regions. Adult male Wistar rats were subjected to intermittent ethanol vapor (14 hours on / 10 hours off) or air exposure for two weeks and were then tested at three time points corresponding to acute withdrawal (8–12 hours into withdrawal) and protracted withdrawal (30 and 60 days of withdrawal) in the FST. The behaviors that were measured in the five minute FST consisted of latency to immobility, swim time, immobility time and climbing time. The FST results showed that the vapor-exposed animals displayed depressive-like behaviors, for instance decreased latency to immobility in acute withdrawal and decreased latency to immobility, decreased swim time and increased immobility time in protracted withdrawal, with differences between air- and vapor-exposed animals becoming more pronounced over the 60 day withdrawal period. NPY levels in the frontal cortex of the vapor-exposed animals were decreased compared to the control animals and CRF levels in the amygdala were correlated with increased immobility time. Thus, extended ethanol vapor exposure produced long-lasting changes in FST behavior and NPY levels in the brain. PMID:20705420

  2. The distribution of neuropeptide Y and dynorphin immunoreactivity in the brain and pituitary gland of the platyfish, Xiphophorus maculatus, from birth to sexual maturity

    Science.gov (United States)

    Cepriano, L. M.; Schreibman, M. P.

    1993-01-01

    Immunoreactive neuropeptide Y and dynorphin have been localized in the brain and pituitary gland of the platyfish, Xiphophorus maculatus, at different ages and stages of development from birth to sexual maturity. Immunoreactive neuropeptide Y was found in perikarya and tracts of the nucleus olfactoretinalis, telencephalon, ventral tegmentum and in the neurohypophysis and in the three regions of the adenohypophysis. Immunoreactive dynorphin was found in nerve tracts in the olfactory bulb and in cells of the pars intermedia and the rostral pars distalis of the pituitary gland.

  3. Effect of subacute benzene exposure on the activity of two neuropeptide-degrading enzymes in the rat brain.

    Science.gov (United States)

    de Gandarias, J M; Casis, O; Irazusta, J; Echevarría, E; Casis, L

    1992-04-01

    Benzene (Bz) is an important industrial chemical, a petroleum by-product, a component of unleaded gas, and thus a ubiquitous environmental pollutant. It is well established that this organic solvent possesses neurotoxic and behavioral effects. However, the neurochemical mechanism of the solvent action remains obscure. The aminopeptidases (AP) are proteolytic enzymes that have been proposed as a candidate regulator of the degradation of several neuropeptides. In this work, changes in Lys- and Leu-aminopeptidase activities in several rat brain regions after benzene administration are described. The AP activity was determined by measuring the rate of hydrolysis of the artificial substrates Lys- and Leu-2-naphthylamides (fluorimetrically detected in triplicate). Both enzyme activities decrease in the thalamus, hypothalamus, hippocampus, and amygdala after Bz treatment. It is suggested that these aminopeptidase activities play a part in the benzene action mechanism, possibly by regulating the activity of several neuroactive peptides.

  4. Porcine brain natriuretic peptide receptor in bovine adrenal cortex

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, K.; Hashiguchi, T.; Ohashi, M.; Takayanagi, R.; Haji, M.; Matsuo, H.; Nawata, H.

    1989-01-01

    The action of porcine brain natriuretic peptide (pBNP) on the steroidogenesis was investigated in cultured bovine adrenocortical cells. Porcine BNP induced a significant dose-dependent inhibition of both ACTH- and A II-stimulated aldosterone secretion. 10/sup /minus/8/M and 10/sup /minus/7/M pBNP also significantly inhibited ACTH-stimulated cortisol and dehydroepiandrosterone (DHEA) secretions. Binding studies of (/sup 125/I)-pBNP to bovine adrenocortical membrane fractions showed that adrenal cortex had high-affinity and low-capacity pBNP binding sites, with a dissociation constant (Kd) of 1.70 x 10/sup /minus/10/M and a maximal binding capacity (Bmax) of 19.9 fmol/mg protein. Finally, the 135 Kd radioactive band was specially visualized in the affinity labeling of bovine adrenal cortex with disuccinimidyl suberate (DSS). These results suggest that pBNP may have receptor-mediated suppressive actions on bovine adrenal steroidogenesis, similar to that in atrial natriuretic peptide (ANP).

  5. Comparative Distribution of Neurons Containing FLFQPQRFamide-like (morphine-modulating) Peptide and Related Neuropeptides in the Rat Brain.

    Science.gov (United States)

    Kivipelto, Leena; Panula, Pertti

    1991-01-01

    FLFQPQRF-NH2 (F8Famide; morphine-modulating peptide), isolated from bovine brain, is an FMRFamide-like peptide with opioid analgesia modulating effects. In the rat brain, F8Famide is immunohistochemically localized in neurons of the medial hypothalamus and medulla oblongata. Neuropeptide Y (NPY) is structurally related to F8Famide and the mammalian FMRFamide-like immunoreactivity (LI) was once thought to be due to an NPY-like peptide. We compared the anatomical distribution of F8Famide-LI with the localization of enkephalin- and NPY-LI-containing structures in the rat brain to find out if NPY or enkephalins coexist with F8Famide-LI. Cryostat sections of colchicine-treated Wistar rat brains were incubated with specific antisera against F8Famide, NPY, YGGFMRGL (Met-enkephalin-Arg-Gly-Leu), or YGGFMRF (Met-enkephalin-Arg-Phe) raised in rabbits. The immunoreactivity was visualized by the peroxidase - antiperoxidase or immunofluorescence method. The light microscopic mirror method was applied to study the colocalization of F8Famide and NPY. The F8Famide-immunoreactivity was concentrated in smaller areas of medial hypothalamus and nucleus of the solitary tract than that of enkephalins and NPY. In all brain areas, the distributions of F8Famide-, enkephalin- and NPY-immunoreactive neurons were distinct. F8Famide-, NPY- and enkephalin-LI-containing nerve terminals were seen in the nucleus of the solitary tract and in the lateral parabrachial nucleus. These results show that the neuronal systems containing F8Famide-, enkephalin- or NPY-LI are anatomically separate in all brain regions. However, there are terminal areas in which more than one type of these immunoreactivities are detected. These results have anatomical correlation with pharmacological reports, suggesting modulatory functions for these peptides on regulation of blood pressure, feeding behaviour and endocrine functions.

  6. Neuropeptides as therapeutic targets in anxiety disorders.

    Science.gov (United States)

    Lin, En-Ju D

    2012-01-01

    In addition to the classical neurotransmitters, neuropeptides represent an important class of modulators for affective behaviors and associated disorders, such as anxiety disorders. Many neuropeptides are abundantly expressed in brain regions involved in emotional processing and anxiety behaviors. Moreover, risk factors for anxiety disorders such as stress modulate the expression of various neuropeptides in the brain. Due to the high prevalence of anxiety disorders and yet limited treatment options, there is a clear need for more effective therapeutics. In this regard, the various neuropeptides represent exciting candidates for new therapeutic designs. In this review, I will provide an up-to-date summary on the evidences for the involvement of seven neuropeptides in anxiety: corticotropin-releasing factor, urocortins, vasopressin, oxytocin, substance P, neuropeptide Y and galanin. This review will cover the behavioral effects of these neuropeptides in animal models of anxiety by both genetic and pharmacological manipulations. Human studies indicating a role for these neuropeptides in anxiety disorders will also be discussed.

  7. Identification, tissue distribution and evaluation of brain neuropeptide Y gene expression in the Brazilian flounder Paralichthys orbignyanus

    Indian Academy of Sciences (India)

    Vinicius F Campos; Tiago Collares; João C Deschamps; Fabiana K Seixas; Odir A Dellagostin; Carlos Frederico C Lanes; Juliana Sandrini; Luis Fernando Marins; Marcelo Okamoto; Luís A Sampaio; Ricardo B Robaldo

    2010-09-01

    Neuropeptide Y (NPY) is one of the most potent stimulants of food intake in vertebrates, mammals and fish. However, the present knowledge about feeding behaviour in fish is still limited and based on studies in a few species. The Brazilian flounder Paralichthys orbignyanus is being considered for aquaculture, and it is important to understand the mechanisms regulating feeding in order to improve its performance in captivity. The objectives of this study were to clone NPY cDNA, evaluate the mRNA levels in different tissues of flounder, and also evaluate brain NPY expression to associate food intake with NPY expression levels. A 597 bp NPY cDNA was cloned from Brazilian flounder brain. NPY expression was detected in all the peripheral tissues analysed. No significant differences were observed in brain NPY gene expression over 24 h after food intake at a temperature of 15 ± 3°C. No correlation was observed among plasma glucose, total protein, cholesterol, triglycerides and NPY expression levels during this 24 h period. On the other hand, mRNA levels were increased after two weeks of fasting at elevated temperatures. Our results suggest that NPY mRNA levels in Brazilian flounder are affected by temperature.

  8. Mescaline-induced changes of brain-cortex ribosomes. Mescaline demethylase activity of brain-cortex soluble supernatant.

    Science.gov (United States)

    Datta, R K; Ghosh, J J

    1977-02-01

    Brain-cortex slices demethylate mescaline and p-methoxyacetanilide, a reference O-demethylating substrate, though the rate of demethylation of mescaline is about one third that of the reference substrate. The demethylase activity is localized mostly in the soluble supernatant (105 000 x g). It is purified 47-fold with respect to the demethylation of mescaline by ammonium sulfate precipitation and DEAE cellulose chromatography. The partially purified demethylase, which is stable for 3-5 days at -5 degrees C in the presence of dithiothreitol and glutathione and is inhibited by p-chloromercuribenzoate, has maximal activity at pH between 7.2 and 8.0. It demethylates mescaline into 3,4-dimethoxy-5-hydroxyphenethylamine and 3,5-dimethoxy-4-hydroxyphenethylamine and some unidentified derivatives.

  9. Migraine and neuropeptides.

    Science.gov (United States)

    Tajti, János; Szok, Délia; Majláth, Zsófia; Tuka, Bernadett; Csáti, Anett; Vécsei, László

    2015-08-01

    Migraine is a common disabling neurovascular primary headache disorder. The pathomechanism is not clear, but extensive preclinical and clinical studies are ongoing. The structural basis of the leading hypothesis is the trigeminovascular system, which includes the trigeminal ganglion, the meningeal vasculature, and the distinct nuclei of the brainstem, the thalamus and the somatosensory cortex. This review covers the effects of sensory (calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide and substance P), sympathetic (neuropeptide Y) and parasympathetic (vasoactive intestinal peptide) migraine-related neuropeptides and the functions of somatostatin, nociceptin and the orexins in the trigeminovascular system. These neuropeptides may take part in neurogenic inflammation (plasma protein extravasation and vasodilatation) of the intracranial vasculature and peripheral and central sensitization of the trigeminal system. The results of human clinical studies are discussed with regard to the alterations in these neuropeptides in the plasma, saliva and cerebrospinal fluid during or between migraine attacks, and the therapeutic possibilities involving migraine-related neuropeptides in the acute and prophylactic treatment of migraine headache are surveyed.

  10. Identification of myotropic neuropeptides from the brain and corpus cardiacum-corpus allatum complex of the beetle, Zophobas atratus.

    Science.gov (United States)

    Marciniak, Pawel; Audsley, Neil; Kuczer, Mariola; Rosinski, Grzegorz

    2010-01-01

    The neuropeptide profiles of the two major neuro-endocrinological organs, brain and retrocerebral complex corpus cardiacum-corpus allatum (CC/CA) of adult beetles, Zophobas atratus Fabricius (Coleoptera:Tenebrionidae) were analyzed by a combination of high performance liquid chromatography (HPLC) and matrix-assisted laser desorption ionization time of flight tandem mass spectrometry (MALDI TOF/TOF MS). The homological semi-isolated heart bioassay was used to screen HPLC fractions for myotropic activity in tissues, revealing several cardiostimulatory and cardioinhibitory factors from both the brain and CC/CA. Analysis of HPLC fractions by MALDI-TOF MS identified seven mass ions that could be assigned to other known peptides: leucomyosuppressin (LMS), Tribolium castaneum pyrokinin 2, sulfakinin 1, myoinhibitory peptide 4, a truncated NVP-like peptide, Tenebrio molitor AKH and crustacean cardioactive peptide. In addition, two novel peptides, myosuppressin (pEDVEHVFLRFa), which differs from LMS by one amino acid (E for D at position 4) and pyrokinin-like peptide (LPHYTPRLa) were also identified. To establish cardioactive properties of some of the identified peptides, chemical synthesis was carried out and their activities were tested using the heart bioassay.

  11. Changes of brain neuropeptide Y and its receptors in rats with flurazepam tolerance and dependence

    Institute of Scientific and Technical Information of China (English)

    Li-ping ZHANG; Li WANG

    2005-01-01

    Aim: Anticonvulsant tolerance and dependence are two obstacles that restrict the clinical use of benzodiazepines (BDZ). In order to explore the mechanism of these two adverse reactions, changes of neuropeptide Y (NPY) and its receptors in the hippocampus of rat models, in relation to flurazepam (FZP, a member of BDZ) tolerance and dependence, were investigated. Methods: The mRNA of preproNPY and its receptors (Y1, Y2, and Y5) in the hippocampus were determined by competitive RT-PCR, and the distribution of NPY in the hippocampus was examined by immunohistochemistry. Results: A decrease of preproNPY mRNA in the hippocampus was foundin tolerant and dependent rats. The level ofpreproNPY mRNA in the hippocampus was reversely correlated with the degree of tolerance and dependence, measured by the threshold of pentylenetetrazol-induced seizures.Immunohistochemistry indicated a decrease of NPY-immunoreactive material in neurons of the CA1, CA3, and dentate gyrus regions of both tolerant and dependent rats. The mRNA of NPY receptors Y1 and Y5 decreased in tolerant rats but did not change in dependent rats. The mRNA of NPY receptor Y2 increased in tolerant rats but decreased in dependent rats. Conclusion: A decrease of NPY in the hippocampus might be involved in anticonvulsant tolerance and dependence following long-term treatment with FZP. Y1, Y2, and Y5 mRNA were also altered in FZP tolerance and dependence.

  12. Postulated Role of Vasoactive Neuropeptide-Related Immunopathology of the Blood Brain Barrier and Virchow-Robin Spaces in the Aetiology of Neurological-Related Conditions

    OpenAIRE

    Staines, D. R.; E. W. Brenu; Marshall-Gradisnik, S.

    2008-01-01

    Vasoactive neuropeptides (VNs) such as pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) have critical roles as neurotransmitters, vasodilators including perfusion and hypoxia regulators, as well as immune and nociception modulators. They have key roles in blood vessels in the central nervous system (CNS) including maintaining functional integrity of the blood brain barrier (BBB) and blood spinal barrier (BSB). VNs are potent activators of aden...

  13. Acute heat stress up-regulates neuropeptide Y precursor mRNA expression and alters brain and plasma concentrations of free amino acids in chicks.

    Science.gov (United States)

    Ito, Kentaro; Bahry, Mohammad A; Hui, Yang; Furuse, Mitsuhiro; Chowdhury, Vishwajit S

    2015-09-01

    Heat stress causes an increase in body temperature and reduced food intake in chickens. Several neuropeptides and amino acids play a vital role in the regulation of food intake. However, the responses of neuropeptides and amino acids to heat-stress-induced food-intake regulation are poorly understood. In the current study, the hypothalamic mRNA expression of some neuropeptides related to food intake and the content of free amino acids in the brain and plasma was examined in 14-day-old chicks exposed to a high ambient temperature (HT; 40±1 °C for 2 or 5 h) or to a control thermoneutral temperature (CT; 30±1 °C). HT significantly increased rectal temperature and plasma corticosterone level and suppressed food intake. HT also increased the expression of neuropeptide Y (NPY) and agouti-signaling protein (ASIP) precursor mRNA, while no change was observed in pro-opiomelanocortin, cholecystokinin, ghrelin, or corticotropin-releasing hormone precursor mRNA. It was further found that the diencephalic content of free amino acids - namely, tryptophan, leucine, isoleucine, valine and serine - was significantly higher in HT chicks with some alterations in their plasma amino acids in comparison with CT chicks. The induction of NPY and ASIP expression and the alteration of some free amino acids during HT suggest that these changes can be the results or causes the suppression of food intake.

  14. Functional differentiation of the premotor cortex : Behavioural and brain imaging studies in humans

    NARCIS (Netherlands)

    Potgieser, Adriaan Remco Ewoud

    2015-01-01

    The premotor cortex is a brain structure that is involved in the preparation of movements. It has an important role in the final integration of task-related information and to funnel this to the primary motor cortex, which subsequently causes the execution of a movement. Premotor areas can also infl

  15. Is the prefrontal cortex especially enlarged in the human brain allometric relations and remapping factors.

    Science.gov (United States)

    Passingham, Richard E; Smaers, Jeroen B

    2014-01-01

    There has been no agreement as to whether the prefrontal cortex is especially enlarged in the human brain. To answer this question, we analyzed the only two datasets that provide information on total prefrontal cortex volume based on cytoarchitectonic criteria. One delineated the prefrontal cortex proper on the basis of cytoarchitectonic criteria; the other used a proxy of the prefrontal cortex based on a cytoarchitectonic delineation of the frontal lobe. To investigate whether all cortical association areas, including the prefrontal cortex, are enlarged in the human brain, we scaled the different areas to a common reference, the primary visual cortex. To investigate whether the prefrontal cortex is more enlarged than other association areas, we scaled it relative to its inputs from and outputs to other nonprimary areas. We carried out separate regression analyses using different data samples as a predictive baseline group: data for monkeys alone informs us on whether great apes are different from monkeys; data for all non-human anthropoids, including great apes, informs us on whether humans are different from all other primates. The analyses show that the value for the human prefrontal cortex is greater than expected, and that this is true even when data for the great apes are included in the analysis. They also show that the chimpanzee prefrontal cortex is greater than expected for a monkey with a similar sized cortex. We discuss possible functional consequences.

  16. Immunocytochemical localization of neuropeptide Y, serotonin, substance P and β-endorphin in optic ganglia and brain of Metapenaeus ensis

    Science.gov (United States)

    Ye, Haihui; Wang, Guizhong; Jin, Zhuxing; Huang, Huiyang; Li, Shaojing

    2006-12-01

    By using immunocytochemistry method of Strept Avidin-Biotin-Complex, four kinds of antisera raised against rabbits were applied to observe the immunoreactive neurons and neuropils of serotonin (5-HT), neuropeptide Y (NPY), substance P (SP) and β-Endorphin (β-Ep) in optic ganglia and brain of Metapenaeus ensis. The results showed that, the 5-HT-immunoreactive cells were located in all the four neuropils of optic ganglia. Immunoreactivity of 5-HT was detected in anterior medial protocerebrum neuropils (AMPN), and the inner and outer lateral beside olfactory lobe (OL) of deutocerebrum. The presence of NPY-immunoreactive cells was found in all the four neuropils of the optic ganglia. NPY-immunoreactivity occurred in the anterior median cell cluster, lateral cell cluster of protocerebrum, and cell cluster beside OL and AMPN. SP-immunoreactivity was found in medulla terminalis (MT) of optic ganglia, and lateral cell cluster of protocerebrum and posterior lateral cell cluster of tritocerebrum. β-Ep-immunoreactive cells were in MT only. In conclusion, these specific distribution patterns of the four immunoreactive substances can be used as morphological clues for understanding their different neurophysiological functions.

  17. Role of 5-hydroxytryptamine in the regulation of brain neuropeptides in normal and diabetic rat

    Science.gov (United States)

    Kolta, Malak G.; Williams, Byron B.; Soliman, Karam F. A.

    1986-01-01

    The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta-E), and immunoreactive insulin was studied in Sprague-Dawley diabetic and control rats. Diabetes was induced using alloxan (45 mg/kg), 15 days prior to sacrificing. Both control and diabetic animals were treated with either p-chlorophenylalanine (PCPA, 300 mg/kg) three days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for three days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindolel acetic acid, while it caused significant increase and decrease in brain beta-E and insulin levels, respectively, in both normal and diabetic rat. Meanwhile, the administration of fluoxetine resulted in significant increase in brain content of 5-HT, DA, NE and insulin but significant decline of beta-E in diabetic and saline control rats. The results of this experiment indicate that 5-HT may be regulating both beta-E and insulin regardless of the availability of pancreatic insulin.

  18. Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery.

    Science.gov (United States)

    Kumar, Manoj; Pandey, Ravi Shankar; Patra, Kartik Chandra; Jain, Sunil Kumar; Soni, Muarai Lal; Dangi, Jawahar Singh; Madan, Jitender

    2013-10-01

    Leucine-enkephalin (Leu-Enk) is a neurotransmitter or neuromodulator in pain transmission. Due to non-addictive opioid analgesic activity of this peptide, it might have great potential in pain management. Leu-Enk loaded N-trimethyl chitosan (TMC) nanoparticles were prepared and evaluated as a brain delivery vehicle via nasal route. TMC biopolymer was synthesized and analyzed by (1)H NMR spectroscopy. TMC nanoparticles were prepared by ionic gelation method. Mean peptide encapsulation efficiency and loading capacity were 78.28±3.8% and 14±1.3%, respectively. Mean particle size, polydispersity index and zeta potential were found to be 443±23 nm, 0.317±0.17 and +15±2 mV respectively for optimized formulations. Apparent permeability coefficient (Papp) of Leu-Enk released from nanoparticles across the porcine nasal mucosa was determined to be 7.45±0.30×10(-6) cm s(-1). Permeability of Leu-Enk released from nanoparticles was 35 fold improved from the nasal mucosa as compared to Leu-Enk solution. Fluorescent microscopy of brain sections of mice showed higher accumulation of fluorescent marker NBD-F labelled Leu-Enk, when administered nasally by TMC nanoparticles, while low brain uptake of marker solution was observed. Furthermore, enhancement in brain uptake resulted into significant improvement in the observed antinociceptive effect of Leu-Enk as evidenced by hot plate and acetic acid induced writhing assay.

  19. Metabolic, gastrointestinal, and CNS neuropeptide effects of brain leptin administration in the rat

    NARCIS (Netherlands)

    Van Dijk, G; Seeley, RJ; Thiele, TE; Friedman, MI; Ji, H; Wilkinson, CW; Burn, P; Campfield, LA; Tenenbaum, R; Baskin, DG; Woods, SC; Schwartz, MW; Seeley, Randy J.; Thiele, Todd E.; Friedman, Mark I.; Wilkinson, Charles W.; Baskin, Denis G.; Woods, Stephen C.; Schwartz, Michael W.

    To investigate whether brain leptin involves neuropeptidergic pathways influencing ingestion, metabolism, and gastrointestinal functioning, leptin (3.5 mu g) was infused daily into the third cerebral ventricular of rats for 3 days. To distinguish between direct leptin effects and those secondary to

  20. Effect of monoamine nervous transmitter and neuropeptide Y in the aged rats with myocardial injury after brain ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the mechanism of myocardial injury after brain ischemia-reperfusion in aged rats from the changes in Dopamine (DA), Noradrenalin (NE), Epinephrine(E) and Neuropeptide Y(NPY).METHODS: Young (5 months) and aged (20 months or more) rats were divided into model groups and normal control groups, respectively. We observed the following items in rats with 60 minute reperfusion after 30 minute brain ischemia: the pathological changed of myocardium, the activities of lactic dehydrrogenase(LDH), creatine phosphokinase(CPK), the contents of NE, DA, E, NPY. RESULTS:The CPK and LDH activities in the young model rats were higher than those in the young control rats was higher than that in the young control rats (P<0.05). The serum CPK activity in the aged control rats was higher than that in the young control rats (P<0.05). The myocardial CPK activity was higher in the aged model rats compared with the young molel rats (P<0.05) and was higher in aged control rats compared with the young control rats (P<0.01). The myocardial LDH activity was lower in the aged control rats than that in the young control rats (P<0.05) and aged model rats (P<0.01). The serum NE level, the level of NE and DA in the hypothalamus were higher obviously than those in the young control rats. The serum NE contents in the two model groups (young and aged) were higher respectively than the two control rats (young and aged). The following items’ contents were higher in the aged model rats than in the young model rats: serum NE, serum E, hypothalamus NE. The hypothalamus NE and E content was lower in the aged model rats than in te aged control rats. NPY level in the brain tissue was lower in the aged control rats than that in the young control rats and aged model rats (P<0.05).CONCLUSION: The myocardial injury after brain ischemia-reperfusion was concerned with the enhanced excitability of sympathetic-adrenal system, espectially in the aged rats. However, the change in myocardial

  1. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

    Directory of Open Access Journals (Sweden)

    Jacqueline C Lieblein-Boff

    Full Text Available Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510 were excluded. In addition, moderate correlations with xenobiotic relationships (2 or those driven by single outliers (3 were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  2. Distribution of neuropeptide FF (NPFF) receptors in correlation with morphine-induced reward in the rat brain.

    Science.gov (United States)

    Wu, Chun-Hung; Tao, Pao-Luh; Huang, Eagle Yi-Kung

    2010-07-01

    Neuropeptide FF (NPFF) exhibited anti-/pro-opioid effects when centrally injected. It was proved to bind to its own receptors, namely NPFF(1) and NPFF(2) receptors, but did not bind to opioid receptors. In our previous study, we found that i.c.v. injected NPFF suppressed morphine-induced conditioned place preference (CPP) in rats, which indicated that NPFF may play a role in the modulation of morphine-induced reward. In the present study, we further investigated the action site of NPFF to attenuate morphine-induced reward. Bilateral intra-VTA (ventral tegmental area) and intra-NAc (nucleus accumbens) injections of NPFF both blocked the CPP caused by morphine in rats. This suggests that NPFF may act at both VTA and NAc to inhibit the sensitization of the mesocorticolimbic dopaminergic pathway. Neurochemical analyses support that NPFF could be acting through the inhibition of the mesocorticolimbic dopaminergic activity increased by morphine. We also determined the distribution of NPFF receptors in rat brains. Our results showed that both NPFF receptors were abundantly expressed in VTA but with less content in NAc. In fluorescent immunohistochemical staining, our results revealed that NPFF(1) and NPFF(2) receptors could be expressed at the TH (tyrosine hydroxylase)- or GAD67 (glutamic acid decarboxylase-67)-positive neurons in VTA, whereas some of them were present in the negative neurons. This implied a possible function of NPFF to modulate dopaminergic neurons directly and a possible indirect action of NPFF on GABAergic neurons to modulate dopamine release. Taken together, our study should be helpful for clarifying the possible mechanisms of NPFF system to modulate morphine-induced reward. Copyright 2010 Elsevier Inc. All rights reserved.

  3. Pivotal role of anterior cingulate cortex in working memory after traumatic brain injury in youth

    Directory of Open Access Journals (Sweden)

    Fabienne eCazalis

    2011-01-01

    Full Text Available In this fMRI study, the functions of the Anterior Cingulate Cortex were studied in a group of adolescents who had sustained a moderate to severe Traumatic Brain Injury. A spatial working memory task with varying working memory loads, representing experimental conditions of increasing difficulty, was administered.In a cross-sectional comparison between the patients and a matched control group, patients performed worse than Controls, showing longer reaction times and lower response accuracy on the spatial working memory task. Brain imaging findings suggest a possible double-dissociation: activity of the Anterior Cingulate Cortex in the Traumatic Brain Injury group, but not in the Control group, was associated with task difficulty; conversely, activity of the left Sensorimotor Cortex in the Control group, but not in the TBI group, was correlated with task difficulty.In addition to the main cross-sectional study, a longitudinal study of a group of adolescent patients with moderate to severe Traumatic Brain Injury was done using fMRI and the same spatial working memory task. The patient group was studied at two time points: one time point during the post-acute phase and one time point 12 months later, during the chronic phase. Results indicated that patients' behavioral performance improved over time, suggesting cognitive recovery. Brain imaging findings suggest that, over this 12 month period, patients recruited less of the Anterior Cingulate Cortex and more of the left Sensorimotor Cortex in response to increasing task difficulty.The role of Anterior Cingulate Cortex in executive functions following a moderate to severe brain injury in adolescence is discussed within the context of conflicting models of the Anterior Cingulate Cortex functions in the existing literature.

  4. Insulin-like growth factor -1 (IGF-1) derived neuropeptides, a novel strategy for the development of pharmaceuticals for managing ischemic brain injury.

    Science.gov (United States)

    Guan, Jian

    2011-08-01

    Insulin-Like Growth Factor-1 (IGF-1) is neuroprotective and improves long-term function after brain injury. However, its clinical application to neurological disorders is limited by its large molecular size, poor central uptake, and mitogenic potential. Glycine-proline-glutamate (GPE) is naturally cleaved from the IGF-1 N-terminal and is also neuroprotective after ischemic injury, thus providing a potential novel strategy of drug discovery for management of neurological disorders. GPE is not enzymatically stable, thus intravenous infusion of GPE becomes necessary for stable and potent neuroprotection. The broad effective dose range and treatment window of 3-7 h after the lesion suggest its potential for treating acute brain injuries. The neuroprotective action of GPE is not age selective, is not dependent on cerebral reperfusion, plasma glucose concentrations, and core body temperature. G-2mPE, a GPE analogue designed to be more resistant to enzymatic activity, has a prolonged plasma half-life and is more potent in neuroprotection. Neuroprotection by GPE and its analogue may be involved in modulation of inflammation, promotion of astrocytosis, inhibition of apoptosis, and in vascular remodeling. Small neuropeptides have advantages over growth factors in the treatment of brain injury, and modified neuropeptides, designed to overcome the limitations of their endogenous counterparts, represent a novel strategy of pharmaceutical discovery for neurological disorders. © 2010 Blackwell Publishing Ltd.

  5. Functional MRI of the brain: localisation of eloquent cortex in focal brain lesion therapy

    Energy Technology Data Exchange (ETDEWEB)

    Dymarkowski, S.; Sunaert, S.; Oostende, S. van; Hecke, P. van; Wilms, G.; Demaerel, P.; Marchal, G. [Department of Radiology, University Hospitals, Leuven (Belgium); Nuttin, B.; Plets, C. [Department of Neurosurgery, University Hospitals, Leuven (Belgium)

    1998-12-01

    The aim of this study was to assess the feasibility of functional MRI (fMRI) in a clinical environment on a large patient group, and to evaluate the pretherapeutic value of localisation of eloquent cortex. Forty patients with focal brain lesions of different origin were studied using fMRI. Functional information was obtained using motor, somatosensory, auditory and phonological stimuli depending on the localisation of the lesions. To obtain information about the spatial accuracy of fMRI, the results were compared with postoperative electrocortical stimulation. Two patients with secondary trigeminal neuralgia were scanned using a motor protocol and were implanted with an extradural plate electrode. Imaging was successful in 40 of 42 patients (including the 2 with trigeminal neuralgia). These patients were analysed for strength of activation, the relation of the lesion to activation sites and the presence of mass effect. The correlation between these data and surgical findings provided significant additional clinical information. Functional MRI can be accurately performed in patients with focal brain lesions using a dedicated approach. Functional MRI offers important clinical information as a contribution to a decrease in posttherapeutic morbidity. The accuracy of the technique can be confirmed by other modalities, including invasive cortical electrostimulation. (orig.) With 7 figs., 2 tabs., 25 refs.

  6. Histamine H3 receptor-mediated inhibition of serotonin release in the rat brain cortex.

    Science.gov (United States)

    Schlicker, E; Betz, R; Göthert, M

    1988-05-01

    Rat brain cortex slices preincubated with 3H-serotonin were superfused with physiological salt solution (containing citalopram, an inhibitor of serotonin uptake) and the effect of histamine on the electrically (3 Hz) evoked 3H overflow was studied. Histamine decreased the evoked overflow in a concentration-dependent manner. The inhibitory effect of histamine was antagonized by impromidine and burimamide, but was not affected by pheniramine, ranitidine, metitepine and phentolamine. Given alone, impromidine facilitated the evoked overflow, whereas burimamide, pheniramine and ranitidine had no effect. The results suggest that histamine inhibits serotonin release in the rat brain cortex via histamine H3 receptors, which may be located presynaptically.

  7. Cellular scaling rules for the brain of Artiodactyla include a highly folded cortex with few neurons

    Directory of Open Access Journals (Sweden)

    Rodrigo eSiqueira Kazu

    2014-11-01

    Full Text Available Quantitative analysis of the cellular composition of rodent, primate, insectivore and afrotherian brains has shown that nonneuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of artiodactyls, a group within the order Cetartiodactyla, believed to be a relatively recent radiation from the common Eutherian ancestor. We find that artiodactyls share nonneuronal scaling rules with all groups analyzed previously. Artiodactyls share with afrotherians and rodents, but not with primates, the neuronal scaling rules that apply to the cerebral cortex and cerebellum. The neuronal scaling rules that apply to the remaining brain areas are however distinct in artiodactyls. Importantly, we show that the folding index of the cerebral cortex scales with the number of neurons in the cerebral cortex in distinct fashions across artiodactyls, afrotherians, rodents, and primates, such that the artiodactyl cerebral cortex is more convoluted than primate cortices of similar numbers of neurons. Our findings suggest that the scaling rules found to be shared across modern afrotherians, glires and artiodactyls applied to the common Eutherian ancestor, such as the relationship between the mass of the cerebral cortex as a whole and its number of neurons. In turn, the distribution of neurons along the surface of the cerebral cortex, which is related to its degree of gyrification, appears to be a clade-specific characteristic. If the neuronal scaling rules for artiodactyls extend to all cetartiodactyls, we predict that the large cerebral cortex of cetaceans will still have fewer neurons than the human cerebral cortex.

  8. Cellular scaling rules for the brain of Artiodactyla include a highly folded cortex with few neurons.

    Science.gov (United States)

    Kazu, Rodrigo S; Maldonado, José; Mota, Bruno; Manger, Paul R; Herculano-Houzel, Suzana

    2014-01-01

    Quantitative analysis of the cellular composition of rodent, primate, insectivore, and afrotherian brains has shown that non-neuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of artiodactyls, a group within the order Cetartiodactyla, believed to be a relatively recent radiation from the common Eutherian ancestor. We find that artiodactyls share non-neuronal scaling rules with all groups analyzed previously. Artiodactyls share with afrotherians and rodents, but not with primates, the neuronal scaling rules that apply to the cerebral cortex and cerebellum. The neuronal scaling rules that apply to the remaining brain areas are, however, distinct in artiodactyls. Importantly, we show that the folding index of the cerebral cortex scales with the number of neurons in the cerebral cortex in distinct fashions across artiodactyls, afrotherians, rodents, and primates, such that the artiodactyl cerebral cortex is more convoluted than primate cortices of similar numbers of neurons. Our findings suggest that the scaling rules found to be shared across modern afrotherians, glires, and artiodactyls applied to the common Eutherian ancestor, such as the relationship between the mass of the cerebral cortex as a whole and its number of neurons. In turn, the distribution of neurons along the surface of the cerebral cortex, which is related to its degree of gyrification, appears to be a clade-specific characteristic. If the neuronal scaling rules for artiodactyls extend to all cetartiodactyls, we predict that the large cerebral cortex of cetaceans will still have fewer neurons than the human cerebral cortex.

  9. The bilingual brain: Flexibility and control in the human cortex

    Science.gov (United States)

    Buchweitz, Augusto; Prat, Chantel

    2013-12-01

    The goal of the present review is to discuss recent cognitive neuroscientific findings concerning bilingualism. Three interrelated questions about the bilingual brain are addressed: How are multiple languages represented in the brain? how are languages controlled in the brain? and what are the real-world implications of experience with multiple languages? The review is based on neuroimaging research findings about the nature of bilingual processing, namely, how the brain adapts to accommodate multiple languages in the bilingual brain and to control which language should be used, and when. We also address how this adaptation results in differences observed in the general cognition of bilingual individuals. General implications for models of human learning, plasticity, and cognitive control are discussed.

  10. Melatonin reduces traumatic brain injury-induced oxidative stress in the cerebral cortex and blood of rats

    OpenAIRE

    Şenol, Nilgün; Nazıroğlu, Mustafa

    2014-01-01

    Free radicals induced by traumatic brain injury have deleterious effects on the function and antioxidant vitamin levels of several organ systems including the brain. Melatonin possesses antioxidant effect on the brain by maintaining antioxidant enzyme and vitamin levels. We investigated the effects of melatonin on antioxidant ability in the cerebral cortex and blood of traumatic brain injury rats. Results showed that the cerebral cortex β-carotene, vitamin C, vitamin E, reduced glutathione, a...

  11. Decoding brain responses to pixelized images in the primary visual cortex: implications for visual cortical prostheses.

    Science.gov (United States)

    Guo, Bing-Bing; Zheng, Xiao-Lin; Lu, Zhen-Gang; Wang, Xing; Yin, Zheng-Qin; Hou, Wen-Sheng; Meng, Ming

    2015-10-01

    Visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only "see" pixelized images, and how to obtain the specific brain responses to different pixelized images in the primary visual cortex (the implant area) is still unknown. We conducted a functional magnetic resonance imaging experiment on normal human participants to investigate the brain activation patterns in response to 18 different pixelized images. There were 100 voxels in the brain activation pattern that were selected from the primary visual cortex, and voxel size was 4 mm × 4 mm × 4 mm. Multi-voxel pattern analysis was used to test if these 18 different brain activation patterns were specific. We chose a Linear Support Vector Machine (LSVM) as the classifier in this study. The results showed that the classification accuracies of different brain activation patterns were significantly above chance level, which suggests that the classifier can successfully distinguish the brain activation patterns. Our results suggest that the specific brain activation patterns to different pixelized images can be obtained in the primary visual cortex using a 4 mm × 4 mm × 4 mm voxel size and a 100-voxel pattern.

  12. Cocaine- and amphetamine-regulated transcript peptide (CART) in the brain of zebra finch, Taeniopygia guttata: Organization, interaction with neuropeptide Y, and response to changes in energy status.

    Science.gov (United States)

    Singh, Omprakash; Kumar, Santosh; Singh, Uday; Kumar, Vinod; Lechan, Ronald M; Singru, Praful S

    2016-10-15

    Cocaine- and amphetamine-regulated transcript (CART) has emerged as a potent anorectic agent. CART is widely distributed in the brain of mammals, amphibians, and teleosts, but the relevant information in avian brain is not available. In birds, CART inhibits food intake, whereas neuropeptide Y (NPY), a well-known orexigenic peptide, stimulates it. How these neuropeptides interact in the brain to regulate energy balance is not known. We studied the distribution of CART-immunoreactivity in the brain of zebra finch, Taeniopygia guttata, its interaction with NPY, and their response to dynamic energy states. CART-immunoreactive fibers were found in the subpallium, hypothalamus, midbrain, and brainstem. Conspicuous CART-immunoreactive cells were observed in the bed nucleus of the stria terminalis, hypothalamic paraventricular, supraoptic, dorsomedial, infundibular (IN), lateral hypothalamic, Edinger-Westphal, and parabrachial nuclei. Hypothalamic sections of fed, fasted, and refed animals were immunostained with cFos, NPY, and CART antisera. Fasting dramatically increased cFos- and NPY-immunoreactivity in the IN, followed by rapid reduction by 2 hours and restoration to normal fed levels 6-10 hours after refeeding. CART-immunoreactive fibers in IN showed a significant reduction during fasting and upregulation with refeeding. Within the IN, double immunofluorescence revealed that 94 ± 2.1% of NPY-immunoreactive neurons were contacted by CART-immunoreactive fibers and 96 ± 2.8% NPY-immunoreactive neurons expressed cFos during fasting. Compared to controls, superfused hypothalamic slices of fasted birds treated with CART-peptide showed a significant reduction (P CART in the brain of T. guttata may perform several functions, and has a particularly important role in the hypothalamic regulation of energy homeostasis. J. Comp. Neurol. 524:3014-3041, 2016. © 2016 Wiley Periodicals, Inc.

  13. Human Development XI: The Structure of the Cerebral Cortex. Are There Really Modules in the Brain?

    Directory of Open Access Journals (Sweden)

    Tyge Dahl Hermansen

    2007-01-01

    Full Text Available The structure of human consciousness is thought to be closely connected to the structure of cerebral cortex. One of the most appreciated concepts in this regard is the Szanthagothei model of a modular building of neo-cortex. The modules are believed to organize brain activity pretty much like a computer. We looked at examples in the literature and argue that there is no significant evidence that supports Szanthagothei's model. We discuss the use of the limited genetic information, the corticocortical afferents termination and the columns in primary sensory cortex as arguments for the existence of the cortex-module. Further, we discuss the results of experiments with Luminization Microscopy (LM colouration of myalinized fibres, in which vertical bundles of afferent/efferent fibres that could support the cortex module are identified. We conclude that sensory maps seem not to be an expression for simple specific connectivity, but rather to be functional defined. We also conclude that evidence for the existence of the postulated module or column does not exist in the discussed material. This opens up for an important discussion of the brain as functionally directed by biological information (information-directed self-organisation, and for consciousness being closely linked to the structure of the universe at large. Consciousness is thus not a local phenomena limited to the brain, but a much more global phenomena connected to the wholeness of the world.

  14. Introduction: Invertebrate Neuropeptides XIV

    Science.gov (United States)

    This publication represents an introduction to the thirteenth in a series of special issues of the Peptides journal dedicated to invertebrate neuropeptides. The issue addresses a number of aspects of invertebrate neuropeptide research including identification of novel invertebrate neuropeptide sequ...

  15. Introduction: Invertebrate Neuropeptides XV

    Science.gov (United States)

    This publication represents an introduction to the fifteenth in a series of special issues of the Peptides journal dedicated to invertebrate neuropeptides. The issue addresses a number of aspects of invertebrate neuropeptide research including identification of novel invertebrate neuropeptide seque...

  16. Introduction: Invertebrate Neuropeptides XIII

    Science.gov (United States)

    This publication represents an introduction to the thirteenth in a series of special issues of the Peptides journal dedicated to invertebrate neuropeptides. The issue addresses a number of aspects of invertebrate neuropeptide research including identification of novel invertebrate neuropeptide sequ...

  17. Introduction: Invertebrate Neuropeptides XVI

    Science.gov (United States)

    This publication represents an introduction to the sixteenth in a series of special issues of the Peptides journal dedicated to invertebrate neuropeptides. The issue addresses a number of aspects of invertebrate neuropeptide research including identification of novel invertebrate neuropeptide seque...

  18. A Study on a Brain-Computer Interface for Motor Assist by Prefrontal Cortex

    Science.gov (United States)

    Misawa, Tadanobu; Takano, Shinya; Shimokawa, Tetsuya; Hirobayashi, Shigeki

    In recent times, considerable research has been conducted on the development of brain-computer interfaces (BCIs). Although there have been several reports on BCIs that assist motor functions by measurement of brain activity in the motor cortex, only a few studies have reported on BCI that assist motor functions by measurement of activity in areas other than the motor cortex. In this study, we experimentally develop a BCI that assists motor functions on the basis of brain activity in the prefrontal cortex. In this BCI system, subjects are shown the labyrinth problem. Concretely, brain activity is measured using fNIRS and the data are acquired in real time. The signal processing module implements low pass filtering of these signals. Further, the pattern classification module used in this system currently is a support vector machine. 22 subjects, both male and female, volunteered to participate in this experiment. 8 of these 22 subjects were able to solve the labyrinth problem. In this experiment, we could not obtain a high distinction. However, these results show that it is possible to develop BCI systems that assist motor functions using information from the prefrontal cortex.

  19. Lithium ameliorates lipopolysaccharide-induced neurotoxicity in the cortex and hippocampus of the adult rat brain.

    Science.gov (United States)

    Khan, Muhammad Sohail; Ali, Tahir; Abid, Muhammad Noman; Jo, Myeung Hoon; Khan, Amjad; Kim, Min Woo; Yoon, Gwang Ho; Cheon, Eun Woo; Rehman, Shafiq Ur; Kim, Myeong Ok

    2017-09-01

    Lithium an effective mood stabilizer, primary used in the treatment of bipolar disorders, has been reported as a protective agent in various neurological disorders. In this study, we examined the neuroprotective role of lithium chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of the adult rat brain. We determined that LiCl -attenuated LPS-induced activated toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear factor-kB (NF-KB) translation factor and various other inflammatory mediators such as interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α). We also analyzed that LiCl significantly abrogated activated gliosis via attenuation of specific markers for activated microglia, ionized calcium-binding adaptor molecule (Iba-1) and astrocytes, glial fibrillary acidic protein (GFAP) in both the cortex and hippocampus of the adult rat brain. Furthermore, we also observed that LiCl treatment significantly ameliorated the increase expression level of apoptotic neurodegeneration protein markers Bax/Bcl2, activated caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1) in the cortex and hippocampus regions of the LPS-treated adult rat brain. In addition, the morphological results of the fluoro-jade B (FJB) and Nissl staining showed that LiCl attenuated the neuronal degeneration in the cortex and hippocampus regions of the LPS-treated adult rat brain. Taken together, our Western blot and morphological results indicated that LiCl significantly prevents the LPS-induced neurotoxicity via attenuation of neuroinflammation and apoptotic neurodegeneration in the cortex and hippocampus of the adult rat brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Topographic organization of the cerebral cortex and brain cartography.

    Science.gov (United States)

    Eickhoff, Simon B; Constable, R Todd; Yeo, B T Thomas

    2017-02-20

    One of the most specific but also challenging properties of the brain is its topographic organization into distinct modules or cortical areas. In this paper, we first review the concept of topographic organization and its historical development. Next, we provide a critical discussion of the current definition of what constitutes a cortical area, why the concept has been so central to the field of neuroimaging and the challenges that arise from this view. A key aspect in this discussion is the issue of spatial scale and hierarchy in the brain. Focusing on in-vivo brain parcellation as a rapidly expanding field of research, we highlight potential limitations of the classical concept of cortical areas in the context of multi-modal parcellation and propose a revised interpretation of cortical areas building on the concept of neurobiological atoms that may be aggregated into larger units within and across modalities. We conclude by presenting an outlook on the implication of this revised concept for future mapping studies and raise some open questions in the context of brain parcellation. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. [The importance of the cortex and subcortical structures of the brain in the perception of acute and chronic pain].

    Science.gov (United States)

    Reschetniak, V K; Kukushkin, M L; Gurko, N S

    2014-01-01

    This review presents the current data in the literature about the importance of the cortex and subcortical structures of the brain in the perception of acute and chronic pain. Discussed the importance of various areas of the brain in perception discriminative and affective components of pain. Discusses also gender differences in pain perception depending on the functional activity of brain cortex and antinociceptive subcortical structures. Analyzed the morphological changes of cortical and subcortical structures of the brain in chronic pain syndromes. It is proved that the decrease in the volume of gray and white matter of cerebral cortex and subcortical structures is a consequence and not the cause of chronic pain syndrome. Discusses the features activate and deactivate certain areas of the cortex of the brain in acute and chronic pain. Analyzed same features the activation of several brain structures in migraine and cluster headache.

  2. Review on Histological and Functional Effect of Aluminium Chloride on Cerebral Cortex of the Brain

    Directory of Open Access Journals (Sweden)

    Birhane Alem Berihu

    2015-08-01

    Full Text Available Various findings are give emphasis to Aluminium has more and more obvious disturbance of the brain other body organs. The purpose of this review is to give a comprehensive report of the existing data on Aluminium induced brain toxicity in different animal models. Along with, we also have made an attempt to present the possible mechanism related to aluminium induced brain toxicity suggested by various researchers. We used 62 different published materials for the compilation of this review article. Google search engine was used for accessing published materials from databases like google scholar, pubmed and hinari. The focus is on Al levels in brain, region-specific and subcellular distribution, mechanism of aluminium on neurotoxicity, histological change and neurobehavioral alternations. The present analysis indicated that AlCl3 showed to be neurotoxin chemical by affecting the biochemical content of brain, histological alternation of cerebral cortex of the brain, disrupting behavioral activities. However, whether aluminium is a sole factor in neurodegeneration, histological alternation of cerebral cortex of the brain still needs to be understood.

  3. Assessment of visual function during brain surgery near the visual cortex by intraoperative optical imaging.

    Science.gov (United States)

    Sobottka, Stephan B; Meyer, Tobias; Kirsch, Matthias; Reiss, Gilfe; Koch, Edmund; Morgenstern, Ute; Schackert, Gabriele

    2013-06-01

    Several functional brain imaging and mapping techniques have been used for the intraoperative identification and preservation of the sensory, motor, and speech areas of the brain. However, intraoperative monitoring and mapping of the visual function is less frequently performed in the clinical routine. To our knowledge, here we demonstrate for the first time that the individual visual cortex can be mapped to the brain surface using a contact-free optical camera system during brain surgery. Intraoperative optical imaging (IOI) was performed by visual stimulation of both eyes using stobe-light flashes. Images were acquired by a camera mounted to a standard surgical microscope. Activity maps could reproducibly be computed by detecting the blood volume-dependent signal changes of the exposed cortex. To the preliminary experience, the new technique seems to be suitable for mapping the visual function in any neurosurgical intervention that requires exposure of the visual cortex. However, the clinical relevance and reliability of the technique need to be confirmed in further studies.

  4. Coupling brain-machine interfaces with cortical stimulation for brain-state dependent stimulation: enhancing motor cortex excitability for neurorehabilitation

    Directory of Open Access Journals (Sweden)

    Alireza eGharabaghi

    2014-03-01

    Full Text Available Motor recovery after stroke is an unsolved challenge despite intensive rehabilitation training programs. Brain stimulation techniques have been explored in addition to traditional rehabilitation training to increase the excitability of the stimulated motor cortex. This modulation of cortical excitability augments the response to afferent input during motor exercises, thereby enhancing skilled motor learning by long-term potentiation-like plasticity. Recent approaches examined brain stimulation applied concurrently with voluntary movements to induce more specific use-dependent neural plasticity during motor training for neurorehabilitation. Unfortunately, such approaches are not applicable for the many severely affected stroke patients lacking residual hand function. These patients require novel activity-dependent stimulation paradigms based on intrinsic brain activity. Here, we report on such brain state-dependent stimulation (BSDS combined with haptic feedback provided by a robotic hand orthosis. Transcranial magnetic stimulation of the motor cortex and haptic feedback to the hand were controlled by sensorimotor desynchronization during motor-imagery and applied within a brain-machine interface environment in one healthy subject and one patient with severe hand paresis in the chronic phase after stroke. BSDS significantly increased the excitability of the stimulated motor cortex in both healthy and post-stroke conditions, an effect not observed in non-BSDS protocols. This feasibility study suggests that closing the loop between intrinsic brain state, cortical stimulation and haptic feedback provides a novel neurorehabilitation strategy for stroke patients lacking residual hand function, a proposal that warrants further investigation in a larger cohort of stroke patients.

  5. Brain-wide map of efferent projections from rat barrel cortex

    Directory of Open Access Journals (Sweden)

    Izabela M. Zakiewicz

    2014-02-01

    Full Text Available The somatotopically organized whisker barrel field of the rat primary somatosensory (S1 cortex is a commonly used model system for anatomical and physiological investigations of sensory processing. The neural connections of the barrel cortex have been extensively mapped. But most investigations have focused on connections to limited regions of the brain, and overviews in the literature of the connections across the brain thus build on a range of material from different laboratories, presented in numerous publications. Furthermore, given the limitations of the conventional journal article format, analyses and interpretations are hampered by lack of access to the underlying experimental data. New opportunities for analyses have emerged with the recent release of an online resource of experimental data consisting of collections of high-resolution images from 6 experiments in which anterograde tracers were injected in S1 whisker or forelimb representations. Building on this material, we have conducted a detailed analysis of the brain wide distribution of the efferent projections of the rat barrel cortex. We compare our findings with the available literature and reports accumulated in the Brain Architecture Management System (BAMS2 database. We report well-known and less known intracortical and subcortical projections of the barrel cortex, as well as distinct differences between S1 whisker and forelimb related projections. Our results correspond well with recently published overviews, but provide additional information about relative differences among S1 projection targets. Our approach demonstrates how collections of shared experimental image data are suitable for brain-wide analysis and interpretation of connectivity mapping data.

  6. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

    Directory of Open Access Journals (Sweden)

    Burkhard Pleger

    Full Text Available The complex regional pain syndrome (CRPS is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1 and motor cortex (M1 contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

  7. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

    Science.gov (United States)

    Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

    2014-01-01

    The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

  8. Distribution of neuropeptide FF-like immunoreactivity in the brain of the lizard Gekko gecko and its relation to catecholaminergic structures.

    Science.gov (United States)

    Smeets, Wilhelmus J A J; López, Jesús M; González, Agustín

    2006-09-01

    The present study provides a detailed description of the distribution of neuropeptide FF (NPFF)-like immunoreactivity in the brain of the lizard Gekko gecko. NPFF is found to be involved in nociception, cardiovascular regulation, and endocrine function. Because of its known relationship with catecholamines in mammals, double staining with tyrosine hydroxylase (TH) antibodies was used to corroborate this for reptiles. The present study revealed that NPFF-like-immunoreactive (NPFF-ir) cells and fibers were widely distributed throughout the brain. Major NPFF-ir cell groups were observed in the diagonal band nucleus of Broca, hypothalamus, and dorsal horn of the spinal cord. Additional cells were found in the anterior olfactory nucleus, lateral and dorsal cortices, dorsolateral septum, and diencephalic intergeniculate leaflet formation. Dense plexuses of NPFF-ir fibers were identified in the diagonal band nucleus of Broca, septum, preoptic and hypothalamic areas, isthmic region, ventrolateral tegmentum, solitary tract nucleus, and dorsolateral funiculus of the spinal cord. Extensive fiber staining also occurred in the nucleus accumbens and the midbrain tectum. Although an intimate relationship between NPFF-ir and TH-ir structures was obvious at many places in the brain, colocalization of these two substances was not observed. In conclusion, the distribution of NPFF in the brain of Gekko shares more features with anamniotes in terms of number of cell groups, more elaborate networks of fibers, and lack of colocalization with catecholamines than with mammals, suggesting a decrease in the distribution of this peptide in the latter vertebrate group.

  9. Expression patterns of the Drosophila neuropeptide CCHamide-2 and its receptor may suggest hormonal signaling from the gut to the brain.

    Directory of Open Access Journals (Sweden)

    Shizhong Li

    Full Text Available The insect neuropeptides CCHamide-1 and -2 are recently discovered peptides that probably occur in all arthropods. Here, we used immunocytochemistry, in situ hybridization, and quantitative PCR (qPCR, to localize the two peptides in the fruitfly Drosophila melanogaster. We found that CCHamide-1 and -2 were localized in endocrine cells of the midgut of larvae and adult flies. These endocrine cells had the appearance of sensory cells, projecting processes close to or into the gut lumen. In addition, CCHamide-2 was also localized in about forty neurons in the brain hemispheres and ventral nerve cord of larvae. Using qPCR we found high expression of the CCHamide-2 gene in the larval gut and very low expression of its receptor gene, while in the larval brain we found low expression of CCHamide-2 and very high expression of its receptor. These expression patterns suggest the following model: Endocrine CCHamide-2 cells in the gut sense the quality of food components in the gut lumen and transmit this information to the brain by releasing CCHamide-2 into the circulation; subsequently, after binding to its brain receptors, CCHamides-2 induces an altered feeding behavior in the animal and possibly other homeostatic adaptations.

  10. Modulation of Tyrosine Hydroxylase, Neuropeptide Y, Glutamate, and Substance P in Ganglia and Brain Areas Involved in Cardiovascular Control after Chronic Exposure to Nicotine

    Directory of Open Access Journals (Sweden)

    Merari F. R. Ferrari

    2011-01-01

    Full Text Available Considering that nicotine instantly interacts with central and peripheral nervous systems promoting cardiovascular effects after tobacco smoking, we evaluated the modulation of glutamate, tyrosine hydroxylase (TH, neuropeptide Y (NPY, and substance P (SP in nodose/petrosal and superior cervical ganglia, as well as TH and NPY in nucleus tractus solitarii (NTS and hypothalamic paraventricular nucleus (PVN of normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHR after 8 weeks of nicotine exposure. Immunohistochemical and in situ hybridization data demonstrated increased expression of TH in brain and ganglia related to blood pressure control, preferentially in SHR, after nicotine exposure. The alkaloid also increased NPY immunoreactivity in ganglia, NTS, and PVN of SHR, in spite of decreasing its receptor (NPY1R binding in NTS of both strains. Nicotine increased SP and glutamate in ganglia. In summary, nicotine positively modulated the studied variables in ganglia while its central effects were mainly constrained to SHR.

  11. Rapid Modulation of Distributed Brain Activity by Transcranial Magnetic Stimulation of Human Motor Cortex

    OpenAIRE

    Lucy Lee; Hartwig Siebner; Sven Bestmann

    2006-01-01

    This paper reviews the effects of single and repetitive transcranial magnetic stimuli (rTMS) delivered to one cortical area and measured across distributed brain regions using electrophysiological measures (e.g. motor thresholds, motor evoked potentials, paired-pulse stimulation), functional neuroimaging (including EEG, PET and fMRI) and behavioural measures. Discussion is restricted to changes in excitability in the primary motor cortex and behaviour during motor tasks following transcranial...

  12. Melatonin reduces traumatic brain injur y-induced oxidative stress in the cerebral cortex and blood of rats

    Institute of Scientific and Technical Information of China (English)

    Nilgnenol; Mustafa Nazrolu

    2014-01-01

    Free radicals induced by traumatic brain injury have deleterious effects on the function and antioxidant vitamin levels of several organ systems including the brain. Melatonin possesses antioxidant effect on the brain by maintaining antioxidant enzyme and vitamin levels. We in-vestigated the effects of melatonin on antioxidant ability in the cerebral cortex and blood of traumatic brain injury rats. Results showed that the cerebral cortex β-carotene, vitamin C, vita-min E, reduced glutathione, and erythrocyte reduced glutathione levels, and plasma vitamin C level were decreased by traumatic brain injury whereas they were increased following melatonin treatment. In conclusion, melatonin seems to have protective effects on traumatic brain inju-ry-induced cerebral cortex and blood toxicity by inhibiting free radical formation and supporting antioxidant vitamin redox system.

  13. Deep brain stimulation reveals emotional impact processing in ventromedial prefrontal cortex

    DEFF Research Database (Denmark)

    Gjedde, Albert; Geday, Jacob

    2009-01-01

    We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin......-noradrenaline reuptake sites. We tested the hypothesis in patients with Parkinson's disease in whom we had measured the changes of blood flow everywhere in the brain associated with the deep brain stimulation of the subthalamic nucleus. We determined the emotional reactivity of the patients as the average impact...... of emotive images rated by the patients off the DBS. We then searched for sites in the brain that had significant correlation of the changes of blood flow with the emotional impact rated by the patients. The results indicate a significant link between the emotional impact when patients are not stimulated...

  14. Neuropeptide complexity in the crustacean central olfactory pathway: immunolocalization of A-type allatostatins and RFamide-like peptides in the brain of a terrestrial hermit crab

    Science.gov (United States)

    2012-01-01

    Background In the olfactory system of malacostracan crustaceans, axonal input from olfactory receptor neurons associated with aesthetascs on the animal’s first pair of antennae target primary processing centers in the median brain, the olfactory lobes. The olfactory lobes are divided into cone-shaped synaptic areas, the olfactory glomeruli where afferents interact with local olfactory interneurons and olfactory projection neurons. The local olfactory interneurons display a large diversity of neurotransmitter phenotypes including biogenic amines and neuropeptides. Furthermore, the malacostracan olfactory glomeruli are regionalized into cap, subcap, and base regions and these compartments are defined by the projection patterns of the afferent olfactory receptor neurons, the local olfactory interneurons, and the olfactory projection neurons. We wanted to know how neurons expressing A-type allatostatins (A-ASTs; synonym dip-allatostatins) integrate into this system, a large family of neuropeptides that share the C-terminal motif –YXFGLamide. Results We used an antiserum that was raised against the A-type Diploptera punctata (Dip)-allatostatin I to analyse the distribution of this peptide in the brain of a terrestrial hermit crab, Coenobita clypeatus (Anomura, Coenobitidae). Allatostatin A-like immunoreactivity (ASTir) was widely distributed in the animal’s brain, including the visual system, central complex and olfactory system. We focussed our analysis on the central olfactory pathway in which ASTir was abundant in the primary processing centers, the olfactory lobes, and also in the secondary centers, the hemiellipsoid bodies. In the olfactory lobes, we further explored the spatial relationship of olfactory interneurons with ASTir to interneurons that synthesize RFamide-like peptides. We found that these two peptides are present in distinct populations of local olfactory interneurons and that their synaptic fields within the olfactory glomeruli are also mostly

  15. Neuropeptide complexity in the crustacean central olfactory pathway: immunolocalization of A-type allatostatins and RFamide-like peptides in the brain of a terrestrial hermit crab

    Directory of Open Access Journals (Sweden)

    Polanska Marta A

    2012-09-01

    Full Text Available Abstract Background In the olfactory system of malacostracan crustaceans, axonal input from olfactory receptor neurons associated with aesthetascs on the animal’s first pair of antennae target primary processing centers in the median brain, the olfactory lobes. The olfactory lobes are divided into cone-shaped synaptic areas, the olfactory glomeruli where afferents interact with local olfactory interneurons and olfactory projection neurons. The local olfactory interneurons display a large diversity of neurotransmitter phenotypes including biogenic amines and neuropeptides. Furthermore, the malacostracan olfactory glomeruli are regionalized into cap, subcap, and base regions and these compartments are defined by the projection patterns of the afferent olfactory receptor neurons, the local olfactory interneurons, and the olfactory projection neurons. We wanted to know how neurons expressing A-type allatostatins (A-ASTs; synonym dip-allatostatins integrate into this system, a large family of neuropeptides that share the C-terminal motif –YXFGLamide. Results We used an antiserum that was raised against the A-type Diploptera punctata (Dip-allatostatin I to analyse the distribution of this peptide in the brain of a terrestrial hermit crab, Coenobita clypeatus (Anomura, Coenobitidae. Allatostatin A-like immunoreactivity (ASTir was widely distributed in the animal’s brain, including the visual system, central complex and olfactory system. We focussed our analysis on the central olfactory pathway in which ASTir was abundant in the primary processing centers, the olfactory lobes, and also in the secondary centers, the hemiellipsoid bodies. In the olfactory lobes, we further explored the spatial relationship of olfactory interneurons with ASTir to interneurons that synthesize RFamide-like peptides. We found that these two peptides are present in distinct populations of local olfactory interneurons and that their synaptic fields within the olfactory

  16. Postulated vasoactive neuropeptide immunopathology affecting the blood–brain/blood–spinal barrier in certain neuropsychiatric fatigue-related conditions: A role for phosphodiesterase inhibitors in treatment?

    Directory of Open Access Journals (Sweden)

    Sonya Marshall-Gradisnik

    2008-10-01

    Full Text Available Donald R Staines1,2, Ekua W Brenu2, Sonya Marshall-Gradisnik21Queensland Health, Gold Coast Population Health Unit, Southport, Gold Coast, Queensland, Australia; 2Faculty of Health Science and Medicine, Population Health and Neuroimmunology Unit, Bond University, Robina, Queensland, AustraliaAbstract: Neuropsychiatric symptoms occur in a number of neurological fatigue-related conditions including multiple sclerosis (MS, Parkinson’s disease (PD, amyotrophic lateral sclerosis (ALS, and chronic fatigue syndrome (CFS. These conditions have been attributed variably to neuroinflammatory and neurodegenerative processes. While autoimmune pathology, at least in part, has long been suspected in these conditions proof has been elusive. Autoimmune pathomechanisms affecting the blood–brain barrier (BBB or blood–spinal barrier (BSB may predispose the BBB/BSB to ‘leakiness’ and be a precursor to additional autoimmune events resulting in neuroinflammatory or neurodegenerative processes. The aim of the paper is to postulate immunopathology of the cerebrospinal perivascular compartment involving certain vasoactive neuropeptides, specifically pituitary adenylate cyclase-activating polypeptide (PACAP and vasoactive intestinal peptide (VIP, in the etiology of certain neuropsychiatric fatigue-related conditions such as MS, ALS, PD, and CFS. Vasoactive neuropeptides (VNs such as PACAP and VIP have critical roles as neurotransmitters, vasodilators including perfusion and hypoxia regulators, and immune and nociception modulators. PACAP and VIP are widely distributed in the central nervous system (CNS and have key roles in CNS blood vessels including maintaining functional integrity of the BBB and BSB. Autoimmunity affecting these VNs would likely have a detrimental effect on BBB and BSB functioning arguably predisposing to further pathological processes. Virchow–Robin spaces (VRS are perivascular compartments surrounding small vessels within the CNS which

  17. Differential distribution and energy status-dependent regulation of the four CART neuropeptide genes in the zebrafish brain.

    Science.gov (United States)

    Akash, G; Kaniganti, Tarun; Tiwari, Neeraj Kumar; Subhedar, Nishikant K; Ghose, Aurnab

    2014-07-01

    The cocaine- and amphetamine-regulated transcript (CART) neuropeptide has been implicated in the neural regulation of energy homeostasis across vertebrate phyla. By using gene-specific in situ hybridization, we have mapped the distribution of the four CART mRNAs in the central nervous system of the adult zebrafish. The widespread neuronal expression pattern for CART 2 and 4 suggests a prominent role for the peptide in processing sensory information from diverse modalities including olfactory and visual inputs. In contrast, CART 1 and 3 have a much more restricted distribution, predominantly located in the nucleus of the medial longitudinal fasciculus (NMLF) and entopeduncular nucleus (EN), respectively. Enrichment of CART 2 and 4 in the preoptic and tuberal areas emphasizes the importance of CART in neuroendocrine functions. Starvation resulted in a significant decrease in CART-positive cells in the nucleus recessus lateralis (NRL) and nucleus lateralis tuberis (NLT) hypothalamic regions, suggesting a function in energy homeostasis for these neurons. Similarly, the EN emerges as a novel energy status-responsive region. Not only is there abundant and overlapping expression of CART 2, 3, and 4 in the EN, but also starvation induced a decrease in CART-expressing neurons in this region. The cellular resolution mapping of CART mRNA and the response of CART-expressing nuclei to starvation underscores the importance of CART neuropeptide in energy processing. Additionally, the regional and gene-specific responses to energy levels suggest a complex, interactive network whereby the four CART gene products may have nonredundant functions in energy homeostasis.

  18. Hypothalamic neuropeptides and the regulation of appetite.

    Science.gov (United States)

    Parker, Jennifer A; Bloom, Stephen R

    2012-07-01

    Neuropeptides released by hypothalamic neurons play a major role in the regulation of feeding, acting both within the hypothalamus, and at other appetite regulating centres throughout the brain. Where classical neurotransmitters signal only within synapses, neuropeptides diffuse over greater distances affecting both nearby and distant neurons expressing the relevant receptors, which are often extrasynaptic. As well as triggering a behavioural output, neuropeptides also act as neuromodulators: altering the response of neurons to both neurotransmitters and circulating signals of nutrient status. The mechanisms of action of hypothalamic neuropeptides with established roles in feeding, including melanin-concentrating hormone (MCH), the orexins, α-melanocyte stimulating hormone (α-MSH), agouti-gene related protein (AgRP), neuropeptide Y, and oxytocin, are reviewed in this article, with emphasis laid on both their effects on appetite regulating centres throughout the brain, and on examining the evidence for their physiological roles. In addition, evidence for the involvement of several putative appetite regulating hypothalamic neuropeptides is assessed including, ghrelin, cocaine and amphetamine-regulated transcript (CART), neuropeptide W and the galanin-like peptides. This article is part of a Special Issue entitled 'Central control of Food Intake'.

  19. Cellular resolution optical access to brain regions in fissures: imaging medial prefrontal cortex and grid cells in entorhinal cortex.

    Science.gov (United States)

    Low, Ryan J; Gu, Yi; Tank, David W

    2014-12-30

    In vivo two-photon microscopy provides the foundation for an array of powerful techniques for optically measuring and perturbing neural circuits. However, challenging tissue properties and geometry have prevented high-resolution optical access to regions situated within deep fissures. These regions include the medial prefrontal and medial entorhinal cortex (mPFC and MEC), which are of broad scientific and clinical interest. Here, we present a method for in vivo, subcellular resolution optical access to the mPFC and MEC using microprisms inserted into the fissures. We chronically imaged the mPFC and MEC in mice running on a spherical treadmill, using two-photon laser-scanning microscopy and genetically encoded calcium indicators to measure network activity. In the MEC, we imaged grid cells, a widely studied cell type essential to memory and spatial information processing. These cells exhibited spatially modulated activity during navigation in a virtual reality environment. This method should be extendable to other brain regions situated within deep fissures, and opens up these regions for study at cellular resolution in behaving animals using a rapidly expanding palette of optical tools for perturbing and measuring network structure and function.

  20. Convergence of sensory systems in the orbitofrontal cortex in primates and brain design for emotion.

    Science.gov (United States)

    Rolls, Edmund T

    2004-11-01

    In primates, stimuli to sensory systems influence motivational and emotional behavior via neural relays to the orbitofrontal cortex. This article reviews studies on the effects of stimuli from multiple sensory modalities on the brain of humans and some other higher primates. The primate orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odors is represented. A somatosensory input is revealed by neurons that respond to the viscosity of food in the mouth, to the texture (mouth feel) of fat in the mouth, and to the temperature of liquids placed into the mouth. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas. Information about each of these modalities is represented separately by different neurons, but in addition, other neurons show convergence between different types of sensory input. This convergence occurs by associative learning between the visual or olfactory input and the taste. In that emotions can be defined as states elicited by reinforcers, the neurons that respond to primary reinforcers (such as taste and touch), as well as learn associations to visual and olfactory stimuli that become secondary reinforcers, provide a basis for understanding the functions of the orbitofrontal cortex in emotion. In complementary neuroimaging studies in humans, it is being found that areas of the orbitofrontal cortex are activated by pleasant touch, by painful touch, by taste, by smell, and by more abstract reinforcers such as winning or losing money. Damage to the orbitofrontal cortex in humans can impair the learning and reversal of stimulus-reinforcement associations and thus the correction of behavioral responses when these are no longer appropriate because previous reinforcement contingencies

  1. Complex plastic changes in the neuropeptide Y system during ethanol intoxication and withdrawal in the rat brain

    DEFF Research Database (Denmark)

    Olling, J D; Ulrichsen, J; Christensen, D Z;

    2009-01-01

    and NPY-stimulated [(35)S]GTPgammaS functional binding. Rats received intragastric ethanol repeatedly for 4 days, and the NPY system was studied in the hippocampal dentate gyrus (DG), CA3, CA1, and piriform cortex (PirCx) and neocortex (NeoCx) during intoxication, peak withdrawal (16 hr), late withdrawal...

  2. Investigation of Higher Brain Functions in Music Composition Using Models of the Cortex Based on Physical System Analogies.

    Science.gov (United States)

    Leng, Xiaodan

    The trion model was developed using the Mountcastle organizational principle for the column as the basic neuronal network in the cortex and the physical system analogy of Fisher's ANNNI spin model. An essential feature is that it is highly structured in time and in spatial connections. Simulations of a network of trions have shown that large numbers of quasi-stable, periodic spatial-temporal firing patterns can be excited. Characteristics of these patterns include the quality of being readily enhanced by only a small change in connection strengths, and that the patterns evolve in certain natural sequences from one to another. With only somewhat different parameters than used for studying memory and pattern recognition, much more flowing and intriguing patterns emerged from the simulations. The results were striking when these probabilistic evolutions were mapped onto pitches and instruments to produce music: For example different simple mappings of the same evolution give music having the "flavor" of a minuet, a waltz, folk music, or styles of specific periods. A theme can be learned so that evolutions have this theme and its variations reoccurring more often. That the trion model is a viable model for the coding of musical structure in human composition and perception is suggested. It is further proposed that model is relevant for examining creativity in the higher cognitive functions of mathematics and chess, which are similar to music. An even higher level of cortical organization was modeled by coupling together several trion networks. Further, one of the crucial features of higher brain function, especially in music composition or appreciation, is the role of emotion and mood as controlled by the many neuromodulators or neuropeptides. The MILA model whose underlying basis is zero-level representation of Kac-Moody algebra is used to modulate periodically the firing threshold of each network. Our preliminary results show that the introduction of "neuromodulation

  3. Reward Sensitivity Modulates Brain Activity in the Prefrontal Cortex, ACC and Striatum during Task Switching

    Science.gov (United States)

    Fuentes-Claramonte, Paola; Ávila, César; Rodríguez-Pujadas, Aina; Ventura-Campos, Noelia; Bustamante, Juan C.; Costumero, Víctor; Rosell-Negre, Patricia; Barrós-Loscertales, Alfonso

    2015-01-01

    Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies. PMID:25875640

  4. Neuropeptides in flatworms.

    Science.gov (United States)

    Gustafsson, M K S; Halton, D W; Kreshchenko, N D; Movsessian, S O; Raikova, O I; Reuter, M; Terenina, N B

    2002-11-01

    The use of well-characterized antibodies raised to neuronal signal substances and their application through immunocytochemistry and confocal scanning laser microscopy has revolutionized studies of the flatworm nervous system (NS). Data about flatworm neuropeptides and the spatial relationship between neuropeptides and other neuronal signal substances and muscle fibers are presented. Neuropeptides form a large part of the flatworm NS. Neuropeptides are especially important as myoexcitatory transmitters or modulators, controlling the musculature of the attachment organs, the stomatogastric and the reproductive systems.

  5. BIASED AGONISM OF THREE DIFFERENT CANNABINOID RECEPTOR AGONISTS IN MOUSE BRAIN CORTEX

    Directory of Open Access Journals (Sweden)

    Rebeca Diez-Alarcia

    2016-11-01

    Full Text Available Cannabinoid receptors are able to couple to different families of G-proteins when activated by an agonist drug. It has been suggested that different intracellular responses may be activated depending on the ligand. The goal of the present study was to characterize the pattern of G protein subunit stimulation triggered by three different cannabinoid ligands, THC, WIN55212-2 and ACEA in mouse brain cortex.Stimulation of the [35S]GTPS binding coupled to specific immunoprecipitation with antibodies against different subtypes of G proteins (Gαi1, Gαi2, Gαi3, Gαo, Gαz, Gαs, Gαq/11, and Gα12/13, in the presence of Δ9-THC, WIN55212-2 and ACEA (submaximal concentration 10 µM was determined by Scintillation Proximity Assay (SPA technique in mouse cortex of wild type, CB1 knock-out, CB2 knock-out and CB1/CB2 double knock-out mice. Results show that, in mouse brain cortex, cannabinoid agonists are able to significantly stimulate not only the classical inhibitory Gαi/o subunits but also other G subunits like Gαz, Gαq/11, and Gα12/13. Moreover, the specific pattern of G protein subunit activation is different depending on the ligand. In conclusion, our results demonstrate that, in mice brain native tissue, different exogenous cannabinoid ligands are able to selectively activate different inhibitory and non-inhibitory Gα protein subtypes, through the activation of CB1 and/or CB2 receptors. Results of the present study may help to understand the specific molecular pathways involved in the pharmacological effects of cannabinoid-derived drugs.

  6. Mitochondrial dysfunction in brain cortex mitochondria of STZ-diabetic rats: effect of l-Arginine.

    Science.gov (United States)

    Ortiz, M Del Carmen; Lores-Arnaiz, Silvia; Albertoni Borghese, M Florencia; Balonga, Sabrina; Lavagna, Agustina; Filipuzzi, Ana Laura; Cicerchia, Daniela; Majowicz, Monica; Bustamante, Juanita

    2013-12-01

    Mitochondrial dysfunction has been implicated in many diseases, including diabetes. It is well known that oxygen free radical species are produced endogenously by mitochondria, and also nitric oxide (NO) by nitric oxide synthases (NOS) associated to mitochondrial membranes, in consequence these organelles constitute main targets for oxidative damage. The aim of this study was to analyze mitochondrial physiology and NO production in brain cortex mitochondria of streptozotocin (STZ) diabetic rats in an early stage of diabetes and the potential effect of L-arginine administration. The diabetic condition was characterized by a clear hyperglycaemic state with loose of body weight after 4 days of STZ injection. This hyperglycaemic state was associated with mitochondrial dysfunction that was evident by an impairment of the respiratory activity, increased production of superoxide anion and a clear mitochondrial depolarization. In addition, the alteration in mitochondrial physiology was associated with a significant decrease in both NO production and nitric oxide synthase type I (NOS I) expression associated to the mitochondrial membranes. An increased level of thiobarbituric acid-reactive substances (TBARS) in brain cortex homogenates from STZ-diabetic rats indicated the presence of lipid peroxidation. L-arginine treatment to diabetic rats did not change blood glucose levels but significantly ameliorated the oxidative stress evidenced by lower TBARS and a lower level of superoxide anion. This effect was paralleled by improvement of mitochondrial respiratory function and a partial mitochondrial repolarization.In addition, the administration of L-arginine to diabetic rats prevented the decrease in NO production and NOSI expression. These results could indicate that exogenously administered L-arginine may have beneficial effects on mitochondrial function, oxidative stress and NO production in brain cortex mitochondria of STZ-diabetic rats.

  7. Biased Agonism of Three Different Cannabinoid Receptor Agonists in Mouse Brain Cortex

    Science.gov (United States)

    Diez-Alarcia, Rebeca; Ibarra-Lecue, Inés; Lopez-Cardona, Ángela P.; Meana, Javier; Gutierrez-Adán, Alfonso; Callado, Luis F.; Agirregoitia, Ekaitz; Urigüen, Leyre

    2016-01-01

    Cannabinoid receptors are able to couple to different families of G proteins when activated by an agonist drug. It has been suggested that different intracellular responses may be activated depending on the ligand. The goal of the present study was to characterize the pattern of G protein subunit stimulation triggered by three different cannabinoid ligands, Δ9-THC, WIN55212-2, and ACEA in mouse brain cortex. Stimulation of the [35S]GTPγS binding coupled to specific immunoprecipitation with antibodies against different subtypes of G proteins (Gαi1, Gαi2, Gαi3, Gαo, Gαz, Gαs, Gαq/11, and Gα12/13), in the presence of Δ9-THC, WIN55212-2 and ACEA (submaximal concentration 10 μM) was determined by scintillation proximity assay (SPA) technique in mouse cortex of wild type, CB1 knock-out, CB2 knock-out and CB1/CB2 double knock-out mice. Results show that, in mouse brain cortex, cannabinoid agonists are able to significantly stimulate not only the classical inhibitory Gαi/o subunits but also other G subunits like Gαz, Gαq/11, and Gα12/13. Moreover, the specific pattern of G protein subunit activation is different depending on the ligand. In conclusion, our results demonstrate that, in mice brain native tissue, different exogenous cannabinoid ligands are able to selectively activate different inhibitory and non-inhibitory Gα protein subtypes, through the activation of CB1 and/or CB2 receptors. Results of the present study may help to understand the specific molecular pathways involved in the pharmacological effects of cannabinoid-derived drugs. PMID:27867358

  8. Imaging studies in congenital anophthalmia reveal preservation of brain architecture in 'visual' cortex.

    Science.gov (United States)

    Bridge, Holly; Cowey, Alan; Ragge, Nicola; Watkins, Kate

    2009-12-01

    The functional specialization of the human brain means that many regions are dedicated to processing a single sensory modality. When a modality is absent, as in congenital total blindness, 'visual' regions can be reliably activated by non-visual stimuli. The connections underlying this functional adaptation, however, remain elusive. In this study, using structural and diffusion-weighted magnetic resonance imaging, we investigated the structural differences in the brains of six bilaterally anophthalmic subjects compared with sighted subjects. Surprisingly, the gross structural differences in the brains were small, even in the occipital lobe where only a small region of the primary visual cortex showed a bilateral reduction in grey matter volume in the anophthalmic subjects compared with controls. Regions of increased cortical thickness were apparent on the banks of the Calcarine sulcus, but not in the fundus. Subcortically, the white matter volume around the optic tract and internal capsule in anophthalmic subjects showed a large decrease, yet the optic radiation volume did not differ significantly. However, the white matter integrity, as measured with fractional anisotropy showed an extensive reduction throughout the brain in the anophthalmic subjects, with the greatest difference in the optic radiations. In apparent contradiction to the latter finding, the connectivity between the lateral geniculate nucleus and primary visual cortex measured with diffusion tractography did not differ between the two populations. However, these findings can be reconciled by a demonstration that at least some of the reduction in fractional anisotropy in the optic radiation is due to an increase in the strength of fibres crossing the radiations. In summary, the major changes in the 'visual' brain in anophthalmic subjects may be subcortical, although the evidence of decreased fractional anisotropy and increased crossing fibres could indicate considerable re-organization.

  9. Binding of mescaline with subcellular fractions upon incubation of brain cortex slices with [14C] mescaline.

    Science.gov (United States)

    Datta, R K; Antopol, W; Ghosh, J J

    1977-01-01

    Incubation of brain cortex slices in the presence of glucose resulted in the permeation of about 65% of [14C] mescaline into slices. Of this, about one-third radioactivity was bound with nuclei, mitochondria, microsomes, and ribosomes. Dialysis of subcellular fractions did not markedly reduce the amounts of radioactivity bound to the fractions. The permeation into slices and the binding of mescaline to subcellular fractions were fairly time-dependent, but were inhibited by the presence of potassium cyanide, or by the absence of glucose and by heating to 80 degrees C for 1 min.

  10. Severe cell reduction in the future brain cortex in human growth-restricted fetuses and infants

    DEFF Research Database (Denmark)

    Samuelsen, Grethe B; Pakkenberg, Bente; Bogdanović, Nenad;

    2007-01-01

    OBJECTIVE: The objective of the study was to test the hypothesis that the total number of cells in the cortical part of the cerebral wall is the same in intrauterine growth-restricted (IUGR) fetuses, compared with normally grown fetuses. STUDY DESIGN: The total cell number in the cerebral wall...... with controls. The daily increase in brain cells in the future cortex was only half of that of the controls. In the 3 other developmental zones, no significant differences in cell numbers could be demonstrated. CONCLUSIONS: IUGR in humans is associated with a severe reduction in cortical growth...

  11. Neuropeptides in Alzheimer's disease: from pathophysiological mechanisms to therapeutic opportunities.

    Science.gov (United States)

    Van Dam, Debby; Van Dijck, Annemie; Janssen, Leen; De Deyn, Peter Paul

    2013-06-01

    Neuropeptides are found throughout the entire nervous system where they can act as neurotransmitter, neuromodulator or neurohormone. In those functions, they play important roles in the regulation of cognition and behavior. In brain disorders like Alzheimer's disease (AD), where abnormal cognition and behavior are observed, the study of neuropeptides is particularly interesting since altered neuropeptides can function as biomarkers or as targets for new medication. In this article neuropeptides with relevance to AD are listed and their influence on cognitive and behavioral disturbances is discussed. Findings from human cerebrospinal fluid and brain tissue, and AD mouse models are described and related to the pathophysiology and symptomatology of the disease. In the past, clinical trials with neuropeptides have often failed due to insufficient delivery to the brain. Therefore, new strategies to target the brain with peptide drugs are also covered.

  12. [Physiology of the neuropeptides].

    Science.gov (United States)

    García-López, M J; Martínez-Martos, J M; Mayas, M D; Carrera, M P; Ramírez- Expósito, M J

    In the present review, the characteristics of mammalian neuropeptides have been studied. Neuropeptides are widely distributed not only in the nervous system but also in the periphery. They are synthesised by neurons as large precursor molecules (pre propeptides) which have to be cleaved and modified in order to form the mature neuropeptides. Neuropeptides may exert actions as neurotransmitters, neuromodulators and/or neurohormones. In the neurons, they coexist with classic transmitters and often with other peptides. After their releasing, they bind to especific receptors to exert their action in the target cell. Most of these receptors belongs to a family of G protein coupled receptors. Finally, peptidases are the enzymes involved in the degradation of neuropeptides. Conclusions. In the last years, the number of known neuropeptides and the understanding of their functions have been increased. With these data, present investigations are looking for the treatment of different pathologies associated with alterations in the physiology of neuropeptides.

  13. Where do the photons collapse - in the retina or in the brain cortex?

    CERN Document Server

    Georgiev, D D

    2002-01-01

    While looking for evidence of quantum coherent states within the brain many quantum mind advocates proposed experiments based on the assumption that the coherence state of natural light could somehow be preserved thorough the neural processing, or in other words they suppose that photons collapse not in the retina, but in the brain cortex. In this paper I show that photons collapse within the retina and subsequent processing of information at the level of neural membranes proceeds. The changes of the membrane potential of the neurons in the primary sensory cortical regions are shown to be relevant to inputting sensory information, which is converted into microtubule subunits pattern and specific quantum states. The role of the associative cortical regions in the conscious experience is thoroughly revised. One of the strangest observations, namely the existence of the so called grandmother cells, is explained by quantum state processing. The question why classical computing is needed at all gets unexpected ans...

  14. Association of Dorsolateral Prefrontal Cortex Dysfunction With Disrupted Coordinated Brain Activity in Schizophrenia: Relationship With Impaired Cognition, Behavioral Disorganization, and Global Function

    National Research Council Canada - National Science Library

    Ursu, Stefan; Minzenberg, Michael J; Walters, Ryan; Wendelken, Carter; Ragland, J. Daniel; Carter, Cameron S; Yoon, Jong H

    2008-01-01

    ... of the dorsolateral prefrontal cortex in schizophrenia patients is associated with disrupted coordinated activity between this prefrontal region and a distributed brain network that supports cognitive control. Method...

  15. Metabolism of cryptic peptides derived from neuropeptide FF precursors: the involvement of insulin-degrading enzyme.

    Science.gov (United States)

    Grasso, Giuseppe; Mielczarek, Przemyslaw; Niedziolka, Magdalena; Silberring, Jerzy

    2014-09-22

    The term "cryptome" refers to the subset of cryptic peptides with bioactivities that are often unpredictable and very different from the parent protein. These cryptic peptides are generated by proteolytic cleavage of proteases, whose identification in vivo can be very challenging. In this work, we show that insulin-degrading enzyme (IDE) is able to degrade specific amino acid sequences present in the neuropeptide pro-NPFFA (NPFF precursor), generating some cryptic peptides that are also observed after incubation with rat brain cortex homogenate. The reported experimental findings support the increasingly accredited hypothesis, according to which, due to its wide substrate selectivity, IDE is involved in a wide variety of physiopathological processes.

  16. Postulated Role of Vasoactive Neuropeptide-Related Immunopathology of the Blood Brain Barrier and Virchow-Robin Spaces in the Aetiology of Neurological-Related Conditions

    Directory of Open Access Journals (Sweden)

    D. R. Staines

    2008-01-01

    Full Text Available Vasoactive neuropeptides (VNs such as pituitary adenylate cyclase-activating polypeptide (PACAP and vasoactive intestinal peptide (VIP have critical roles as neurotransmitters, vasodilators including perfusion and hypoxia regulators, as well as immune and nociception modulators. They have key roles in blood vessels in the central nervous system (CNS including maintaining functional integrity of the blood brain barrier (BBB and blood spinal barrier (BSB. VNs are potent activators of adenylate cyclase and thus also have a key role in cyclic AMP production affecting regulatory T cell and other immune functions. Virchow-Robin spaces (VRSs are perivascular compartments surrounding small vessels within the CNS and contain VNs. Autoimmunity of VNs or VN receptors may affect BBB and VRS function and, therefore, may contribute to the aetiology of neurological-related conditions including multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis. VN autoimmunity will likely affect CNS and immunological homeostasis. Various pharmacological and immunological treatments including phosphodiesterase inhibitors and plasmapheresis may be indicated.

  17. Identification of a tachykinin-related neuropeptide from the honeybee brain using direct MALDI-TOF MS and its gene expression in worker, queen and drone heads.

    Science.gov (United States)

    Takeuchi, H; Yasuda, A; Yasuda-Kamatani, Y; Kubo, T; Nakajima, T

    2003-06-01

    Using a combination of MALDI-TOF and on-line capillary HPLC/Q-Tof mass spectroscopy, we identified and determined the amino acid sequence of a novel neuropeptide in the brain of the honeybee Apis mellifera L., termed AmTRP peptide (Apis mellifera tachykinin-related peptide), related to insect tachykinin. A cDNA for a prepro-protein (prepro-AmTRP) of AmTRP was isolated and determined to encode seven AmTRPs 1-7. Northern blot analysis indicated that the prepro-AmTRP gene is expressed differentially in the nurse bee, forager, queen and drone heads. Strong expression was detected in the queen and forager heads, while weak and almost no significant expression was detected in the nurse and drone heads, respectively. These results suggest that AmTRP peptide functions as a neuromodulator and/or hormone, associated with sex-specific or age/division of labour-selective behaviour and/or physiology of the honeybees.

  18. Immunocytochemical localization of neuropeptide Y,serotonin, substance P and β-endorphin in optic ganglia and brain of Metapenaeus ensis

    Institute of Scientific and Technical Information of China (English)

    YE Haihui; WANG Guizhong; JIN Zhuxing; HUANG Huiyang; LI Shaojing

    2006-01-01

    s By using immunocytochemistry method of Strept Avidin-Biotin-Complex, four kinds of antisera raised against rabbits were applied to observe the immunoreactive neurons and neuropils of serotonin (5-HT), neuropeptide Y (NPY), substance P(SP) and β-Endorphin (β-Ep) in optic ganglia and brain of Metapenaeus ensis. The results showed that, the 5-HT-immunoreactive cells were located in all the four neuropils of optic ganglia. Immunoreactivity of 5-HT was detected in anterior medial protocerebrum neuropils (AMPN), and the inner and outer lateral beside olfactory lobe (OL) of deutocerebrum. The presence of NPY-immunoreactive cells was found in all the four neuropils of the optic ganglia.NPY-immunoreactivity occurred in the anterior median cell cluster, lateral cell cluster of protocerebrum,and cell cluster beside OL and AMPN. SP-immunoreactivity was found in medulla terminalis (MT) of optic ganglia, and lateral cell cluster of protocerebrum and posterior lateral cell cluster of tritocerebrum.β-Ep-immunoreactive cells were in MT only. In conclusion, these specific distribution patterns of the four immunoreactive substances can be used as morphological clues for understanding their different neurophysiological functions.

  19. Gradients in the Brain: The Control of the Development of Form and Function in the Cerebral Cortex

    OpenAIRE

    Sansom, Stephen N; Frederick J Livesey

    2009-01-01

    In the developing brain, gradients are commonly used to divide neurogenic regions into distinct functional domains. In this article, we discuss the functions of morphogen and gene expression gradients in the assembly of the nervous system in the context of the development of the cerebral cortex. The cerebral cortex is a mammal-specific region of the forebrain that functions at the top of the neural hierarchy to process and interpret sensory information, plan and organize tasks, and to control...

  20. Cortex-sparing fiber dissection: an improved method for the study of white matter anatomy in the human brain

    Science.gov (United States)

    Martino, Juan; De Witt Hamer, Philip C; Vergani, Francesco; Brogna, Christian; de Lucas, Enrique Marco; Vázquez-Barquero, Alfonso; García-Porrero, Juan A; Duffau, Hugues

    2011-01-01

    Classical fiber dissection of post mortem human brains enables us to isolate a fiber tract by removing the cortex and overlying white matter. In the current work, a modification of the dissection methodology is presented that preserves the cortex and the relationships within the brain during all stages of dissection, i.e. ‘cortex-sparing fiber dissection’. Thirty post mortem human hemispheres (15 right side and 15 left side) were dissected using cortex-sparing fiber dissection. Magnetic resonance imaging study of a healthy brain was analyzed using diffusion tensor imaging (DTI)-based tractography software. DTI fiber tract reconstructions were compared with cortex-sparing fiber dissection results. The fibers of the superior longitudinal fasciculus (SLF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UF) were isolated so as to enable identification of their cortical terminations. Two segments of the SLF were identified: first, an indirect and superficial component composed of a horizontal and vertical segment; and second, a direct and deep component or arcuate fasciculus. The IFOF runs within the insula, temporal stem and sagittal stratum, and connects the frontal operculum with the occipital, parietal and temporo-basal cortex. The UF crosses the limen insulae and connects the orbito-frontal gyri with the anterior temporal lobe. Finally, a portion of the ILF was isolated connecting the fusiform gyrus with the occipital gyri. These results indicate that cortex-sparing fiber dissection facilitates study of the 3D anatomy of human brain tracts, enabling the tracing of fibers to their terminations in the cortex. Consequently, it is an important tool for neurosurgical training and neuroanatomical research. PMID:21767263

  1. ROI measurement of the signal intensity of precentral cortex in the normal brain

    Energy Technology Data Exchange (ETDEWEB)

    Karaarslan, Ercan E-mail: arzuarslan@netscape.net; Arslan, Arzu

    2004-12-01

    Objective: It has recently been described that perirolandic cortex generally had a low signal intensity (SI) in neurologically normal brain. The aim of this study was to confirm this finding by an objective quantitative study. Materials and methods: Turbo fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images of 24 neurologically normal patients were evaluated retrospectively. Signal intensity measurements of the precentral and superior frontal cortices (SFCs) were obtained at a manually traced irregular region-of-interest (ROI). t-Test for paired samples was used to evaluate the significance of differences between signal intensity measurements. Results: Mean signal intensities of precentral and superior frontal cortices were 349.5 and 380.7, respectively, on the right, and 351.7 and 374.1 on the left hemisphere. The difference between the mean signal intensities of the side-matched precentral and superior frontal cortices was statistically significant (P<0.001). Conclusion: Low signal intensity of the precentral cortex (PCC) in normal brain on turbo FLAIR images is an objective finding, confirmed by ROI measurement.

  2. Transcriptomic Modification in the Cerebral Cortex following Noninvasive Brain Stimulation: RNA-Sequencing Approach

    Directory of Open Access Journals (Sweden)

    Ben Holmes

    2016-01-01

    Full Text Available Transcranial direct current stimulation (tDCS has been shown to modulate neuroplasticity. Beneficial effects are observed in patients with psychiatric disorders and enhancement of brain performance in healthy individuals has been observed following tDCS. However, few studies have attempted to elucidate the underlying molecular mechanisms of tDCS in the brain. This study was conducted to assess the impact of tDCS on gene expression within the rat cerebral cortex. Anodal tDCS was applied at 3 different intensities followed by RNA-sequencing and analysis. In each current intensity, approximately 1,000 genes demonstrated statistically significant differences compared to the sham group. A variety of functional pathways, biological processes, and molecular categories were found to be modified by tDCS. The impact of tDCS on gene expression was dependent on current intensity. Results show that inflammatory pathways, antidepressant-related pathways (GTP signaling, calcium ion binding, and transmembrane/signal peptide pathways, and receptor signaling pathways (serotonergic, adrenergic, GABAergic, dopaminergic, and glutamate were most affected. Of the gene expression profiles induced by tDCS, some changes were observed across multiple current intensities while other changes were unique to a single stimulation intensity. This study demonstrates that tDCS can modify the expression profile of various genes in the cerebral cortex and that these tDCS-induced alterations are dependent on the current intensity applied.

  3. Histamine H3A receptor-mediated inhibition of noradrenaline release in the mouse brain cortex.

    Science.gov (United States)

    Schlicker, E; Behling, A; Lümmen, G; Göthert, M

    1992-04-01

    Mouse brain cortex slices preincubated with 3H-noradrenaline were superfused with physiological salt solution containing desipramine plus a drug with alpha 2-adrenoceptor antagonist properties, and the effects of histamine receptor ligands on the electrically (0.3 Hz) evoked tritium overflow were studied. The evoked overflow (from slices superfused with phentolamine) was inhibited by histamine (pIC35 6.53), the H3 receptor agonist R-(-)-alpha-methylhistamine (7.47) and its S-(+)-enantiomer (5.82) but not influenced by the H1 receptor agonist 2-(2-thiazolyl)-ethylamine 3.2 mumol/l and the H2 receptor agonist dimaprit 10 mumol/l. The inhibitory effect of histamine was not affected by the H1 receptor antagonist dimetindene 1 mumol/l and the H2 receptor antagonist ranitidine 10 mumol/l. The concentration-response curve of histamine (determined in the presence of rauwolscine) was shifted to the right by the H3 receptor antagonists thioperamide (apparent pA2 8.67), impromidine (7.30) and burimamide (6.82) as well as by dimaprit (6.16). The pA2 values of the four drugs were compared with their affinities for H3A and H3B binding sites in rat brain membranes (West et al. 1990 Mol Pharmacol 38:610); a significant correlation was obtained for the H3A, but not for the H3B sites. The results suggest that noradrenaline release in the mouse brain cortex is inhibited by histamine via H3A receptors and that dimaprit is an H3 receptor antagonist of moderate potency.

  4. Circadian oscillators in the mouse brain: molecular clock components in the neocortex and cerebellar cortex.

    Science.gov (United States)

    Rath, Martin F; Rovsing, Louise; Møller, Morten

    2014-09-01

    The circadian timekeeper of the mammalian brain resides in the suprachiasmatic nucleus of the hypothalamus (SCN), and is characterized by rhythmic expression of a set of clock genes with specific 24-h daily profiles. An increasing amount of data suggests that additional circadian oscillators residing outside the SCN have the capacity to generate peripheral circadian rhythms. We have recently shown the presence of SCN-controlled oscillators in the neocortex and cerebellum of the rat. The function of these peripheral brain clocks is unknown, and elucidating this could involve mice with conditional cell-specific clock gene deletions. This prompted us to analyze the molecular clockwork of the mouse neocortex and cerebellum in detail. Here, by use of in situ hybridization and quantitative RT-PCR, we show that clock genes are expressed in all six layers of the neocortex and the Purkinje and granular cell layers of the cerebellar cortex of the mouse brain. Among these, Per1, Per2, Cry1, Arntl, and Nr1d1 exhibit circadian rhythms suggesting that local running circadian oscillators reside within neurons of the mouse neocortex and cerebellar cortex. The temporal expression profiles of clock genes are similar in the neocortex and cerebellum, but they are delayed by 5 h as compared to the SCN, suggestively reflecting a master-slave relationship between the SCN and extra-hypothalamic oscillators. Furthermore, ARNTL protein products are detectable in neurons of the mouse neocortex and cerebellum, as revealed by immunohistochemistry. These findings give reason to further pursue the physiological significance of circadian oscillators in the mouse neocortex and cerebellum.

  5. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex.

    Science.gov (United States)

    Scott, Gregory D; Karns, Christina M; Dow, Mark W; Stevens, Courtney; Neville, Helen J

    2014-01-01

    Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal plasticity), a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case), as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral vs. perifoveal visual stimulation (11-15° vs. 2-7°) in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl's gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl's gyrus) indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral vs. perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory, and multisensory and/or supramodal regions, such as posterior parietal cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal, and multisensory regions, to altered visual processing in congenitally deaf adults.

  6. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex

    Directory of Open Access Journals (Sweden)

    Gregory D. Scott

    2014-03-01

    Full Text Available Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl’s gyrus. In addition to reorganized auditory cortex (cross-modal plasticity, a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case, as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral versus perifoveal visual stimulation (11-15° vs. 2°-7° in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl’s gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl’s gyrus indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral versus perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory and multisensory and/or supramodal regions, such as posterior parietal cortex, frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal and multisensory regions, to altered visual processing in

  7. SEXUAL DIMORPHISM IN VOLUME OF INSULAR CORTEX IN NORMAL AND NEURODEGENERATIVE HUMAN BRAINS : A STEREOLOGIC AND MACROSCOPIC STUDY

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    H. Haghir

    2005-09-01

    Full Text Available Lillie is known about the sexual differences in volume of human insular cortex in normal subjects and those suffering from ncurodcgcncrativc diseases. The objective of this study is 10 investigate the sex difference in volume of the left insular cortex in normal right-handed subjects versus subjects suffering from Alzheimer and Parkinson diseases. This study was performed on 72 normal human brains (38 males. 34 females. II brains suffered from Alzheimer (4 males. 7 females, and 13 brains suffered from Parkinson (9 males, 4 females. The right hemispheres were used for neuropathologic studies. The volumes of the len insular cortex in the male and female normal subjects were 6.65 :.:: 1.55 em: and 5.X3 ,t: 1.12 em'. respectively (P = 0.0 I. The volumes of the left insular cortex in the male and female subjects suffering from Alzheimer were 5.6X :i.: !.49 ern' and 4.49 :i: (l.X6 em'. respectively (P = 0.2 I. The volumes of the left insular cortex in the male and female subjects suffering from Parkinson were 5.99 ± 1.05 em' und 5.37 ::: 0.51 em'. respectively (P =:= O. I8. The present study shows a significant larger left insular cortex volume in normal right-handed males than in females. No significant sexual difference in volume of the left insular cortex in subjects suffering from Alzheimer and Parkinson diseases W,IS observed. Disappearance of the normal sexual dimorphism in the volume of the insular cortex may be due to a more severe degeneration of this conical area in males during thc ncurodcgcncrativc disorders.

  8. [Effects of neuropeptides on interferon production in vitro].

    Science.gov (United States)

    Kul'chikov, A E; Makarenko, A N

    2008-01-01

    The study of an interferon-inducing action of neuropeptides (a cerebrolysin model) on production of interferons by human blood leukocytes has shown that neuropeptides induce gamma-interferon production in the titer 267 IU/ml that determines one of the mechanisms of a neuroimmunocorrecting effect of cerebrolysin (Ebewe, Austria) in many neurological diseases (acute stroke, brain traumas and different neuroinfectious diseases).

  9. Early exposure to urethane anesthesia: Effects on neuronal activity in the piriform cortex of the developing brain.

    Science.gov (United States)

    Kajiwara, Riichi; Takashima, Ichiro

    2015-07-23

    Exposure to urethane anesthesia reportedly produces selective neuronal cell loss in the piriform cortex of young brains; however, resulting functional deficits have not been investigated. The present study found abnormalities in piriform cortex activity of isolated brains in vitro that were harvested from guinea pigs exposed to urethane anesthesia at 14 days of age. Current source density (CSD) analysis and voltage-sensitive dye (VSD) imaging experiments were conducted 48h after urethane injection. We applied paired-pulse stimulation to the lateral olfactory tract (LOT) and assessed short-interval intra-cortical inhibition in the piriform cortex. CSD analysis revealed that a current sink in layer Ib remained active in response to successive stimuli, with an inter-stimulus interval of 30-60 ms, which was typically strongly inhibited. VSD imaging demonstrated stronger and extended neural activity in the urethane-treated piriform cortex, even in response to a second stimulus delivered in short succession. We identified gamma-aminobutyric acid (GABA) ergic neurons in the piriform cortex of sham and urethane-treated animals and found a decrease in GABA-immunoreactive cell density in the urethane group. These results suggest that urethane exposure induces loss of GABAergic interneurons and a subsequent reduction in paired-pulse inhibition in the immature piriform cortex.

  10. Brain state-dependent abnormal LFP activity in the auditory cortex of a schizophrenia mouse model

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    Kazuhito eNakao

    2014-07-01

    Full Text Available In schizophrenia, evoked 40-Hz auditory steady-state responses (ASSRs are impaired, which reflects the sensory deficits in this disorder, and baseline spontaneous oscillatory activity also appears to be abnormal. It has been debated whether the evoked ASSR impairments are due to the possible increase in baseline power. GABAergic interneuron-specific NMDA receptor (NMDAR hypofunction mutant mice mimic some behavioral and pathophysiological aspects of schizophrenia. To determine the presence and extent of sensory deficits in these mutant mice, we recorded spontaneous local field potential (LFP activity and its click-train evoked ASSRs from primary auditory cortex of awake, head-restrained mice. Baseline spontaneous LFP power in the pre-stimulus period before application of the first click trains was augmented at a wide range of frequencies. However, when repetitive ASSR stimuli were presented every 20 sec, averaged spontaneous LFP power amplitudes during the inter-ASSR stimulus intervals in the mutant mice became indistinguishable from the levels of control mice. Nonetheless, the evoked 40-Hz ASSR power and their phase locking to click trains were robustly impaired in the mutants, although the evoked 20-Hz ASSRs were also somewhat diminished. These results suggested that NMDAR hypofunction in cortical GABAergic neurons confers two brain state-dependent LFP abnormalities in the auditory cortex; (1 a broadband increase in spontaneous LFP power in the absence of external inputs, and (2 a robust deficit in the evoked ASSR power and its phase-locking despite of normal baseline LFP power magnitude during the repetitive auditory stimuli. The paradoxically high spontaneous LFP activity of the primary auditory cortex in the absence of external stimuli may possibly contribute to the emergence of schizophrenia-related aberrant auditory perception.

  11. Brain state-dependent abnormal LFP activity in the auditory cortex of a schizophrenia mouse model.

    Science.gov (United States)

    Nakao, Kazuhito; Nakazawa, Kazu

    2014-01-01

    In schizophrenia, evoked 40-Hz auditory steady-state responses (ASSRs) are impaired, which reflects the sensory deficits in this disorder, and baseline spontaneous oscillatory activity also appears to be abnormal. It has been debated whether the evoked ASSR impairments are due to the possible increase in baseline power. GABAergic interneuron-specific NMDA receptor (NMDAR) hypofunction mutant mice mimic some behavioral and pathophysiological aspects of schizophrenia. To determine the presence and extent of sensory deficits in these mutant mice, we recorded spontaneous local field potential (LFP) activity and its click-train evoked ASSRs from primary auditory cortex of awake, head-restrained mice. Baseline spontaneous LFP power in the pre-stimulus period before application of the first click trains was augmented at a wide range of frequencies. However, when repetitive ASSR stimuli were presented every 20 s, averaged spontaneous LFP power amplitudes during the inter-ASSR stimulus intervals in the mutant mice became indistinguishable from the levels of control mice. Nonetheless, the evoked 40-Hz ASSR power and their phase locking to click trains were robustly impaired in the mutants, although the evoked 20-Hz ASSRs were also somewhat diminished. These results suggested that NMDAR hypofunction in cortical GABAergic neurons confers two brain state-dependent LFP abnormalities in the auditory cortex; (1) a broadband increase in spontaneous LFP power in the absence of external inputs, and (2) a robust deficit in the evoked ASSR power and its phase-locking despite of normal baseline LFP power magnitude during the repetitive auditory stimuli. The "paradoxically" high spontaneous LFP activity of the primary auditory cortex in the absence of external stimuli may possibly contribute to the emergence of schizophrenia-related aberrant auditory perception.

  12. Social and asocial prefrontal cortex neurons: a new look at social facilitation and the social brain.

    Science.gov (United States)

    Demolliens, Marie; Isbaine, Faiçal; Takerkart, Sylvain; Huguet, Pascal; Boussaoud, Driss

    2017-08-01

    A fundamental aspect of behavior in many animal species is 'social facilitation', the positive effect of the mere presence of conspecifics on performance. To date, the neuronal counterpart of this ubiquitous phenomenon is unknown. We recorded the activity of single neurons from two prefrontal cortex regions, the dorsolateral part and the anterior cingulate cortex in monkeys as they performed a visuomotor task, either in the presence of a conspecific (Presence condition) or alone. Monkeys performed better in the presence condition than alone (social facilitation), and analyses of outcome-related activity of 342 prefrontal neurons revealed that most of them (86%) were sensitive to the performance context. Two populations of neurons were discovered: 'social neurons', preferentially active under social presence and 'asocial neurons', preferentially active under social isolation. The activity of these neurons correlated positively with performance only in their preferred context (social neurons under social presence; asocial neurons under social isolation), thereby providing a potential neuronal mechanism of social facilitation. More generally, the fact that identical tasks recruited either social or asocial neurons depending on the presence or absence of a conspecific also brings a new look at the social brain hypothesis. © The Author (2017). Published by Oxford University Press.

  13. Increased motor cortex excitability during motor imagery in brain-computer interface trained subjects

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    Olesya eMokienko

    2013-11-01

    Full Text Available Background: Motor imagery (MI is the mental performance of movement without muscle activity. It is generally accepted that MI and motor performance have similar physiological mechanisms.Purpose: To investigate the activity and excitability of cortical motor areas during MI in subjects who were previously trained with an MI-based brain-computer interface (BCI.Subjects and methods: Eleven healthy volunteers without neurological impairments (mean age, 36 years; range: 24–68 years were either trained with an MI-based BCI (BCI-trained, n = 5 or received no BCI training (n = 6, controls. Subjects imagined grasping in a blocked paradigm task with alternating rest and task periods. For evaluating the activity and excitability of cortical motor areas we used functional MRI and navigated transcranial magnetic stimulation (nTMS.Results: fMRI revealed activation in Brodmann areas 3 and 6, the cerebellum, and the thalamus during MI in all subjects. The primary motor cortex was activated only in BCI-trained subjects. The associative zones of activation were larger in non-trained subjects. During MI, motor evoked potentials recorded from two of the three targeted muscles were significantly higher only in BCI-trained subjects. The motor threshold decreased (median = 17% during MI, which was also observed only in BCI-trained subjects.Conclusion: Previous BCI training increased motor cortex excitability during MI. These data may help to improve BCI applications, including rehabilitation of patients with cerebral palsy.

  14. Synthesis of heat shock proteins in rat brain cortex after transient ischemia.

    Science.gov (United States)

    Dienel, G A; Kiessling, M; Jacewicz, M; Pulsinelli, W A

    1986-08-01

    Cell-free protein synthesis and two-dimensional gel autoradiography were used to characterize early postischemic protein synthesis in rat neocortex. Severe forebrain ischemia was induced for 30 min (four-vessel occlusion model) and followed by 3 h of recirculation. Polysomes were isolated from the cerebral cortex, translated in vitro in a reticulocyte system, and analyzed by two-dimensional gel electrophoresis. The translation products of postischemic polysomes included a major new protein family (70 kDa) with multiple isoelectric variants that was found to comigrate with the 68- to 70-kDa "heat shock" protein synthesized from polysomes of hyperthermic rats. Two other stress proteins (93 and 110 kDa) also appeared to be synthesized in increased amounts after ischemia. A complement of proteins that was indistinguishable from that of controls was also synthesized after ischemia, indicating that messenger ribonucleic acid coding for most brain proteins is preserved after ischemia and is bound to polysomes.

  15. Laser speckle-imaging of blood microcirculation in the brain cortex of laboratory rats in stress

    Energy Technology Data Exchange (ETDEWEB)

    Vilensky, M A; Semyachkina-Glushkovskaya, Oxana V; Timoshina, P A; Kuznetsova, Jana V; Semyachkin-Glushkovskii, I A; Agafonov, Dmitry N; Tuchin, Valerii V

    2012-06-30

    The results of experimental approbation of the method of laser full-field speckle-imaging for monitoring the changes in blood microcirculation state of the brain cortex of laboratory rats under the conditions of developing stroke and administration of vasodilating and vasoconstrictive agents are presented. The studies aimed at the choice of the optimal conditions of speckle-image formation and recording were performed and the software implementing an adaptive algorithm for processing the data of measurements was created. The transfer of laser radiation to the probed region of the biotissue was implemented by means of a silica-polymer optical fibre. The problems and prospects of speckle-imaging of cerebral microcirculation of blood in laboratory and clinical conditions are discussed.

  16. Increased prevalence of Chlamydophila DNA in post-mortem brain frontal cortex from patients with schizophrenia.

    Science.gov (United States)

    Fellerhoff, Barbara; Wank, Rudolf

    2011-07-01

    Infection can initiate symptoms of mental illness. It has been shown previously that Chlamydophila DNA is present six times more often in the blood of patients with schizophrenia than in the blood of control individuals. Monocytes, the main targets of Chlamydiaceae infection, are microglia precursors. We identified Chlamydiaceae infection using blinded brain DNA samples derived from the frontal cortex. Using PCR and sequence analysis, we found Chlamydophila DNA to be four times greater in patients with schizophrenia than in controls (schizophrenia: N=34, microbial DNA frequency 23.5%; controls: N=35, microbial DNA frequency 5.7%; P=0.045, OR=5.08). Persistent Chlamydophila-infected microglia or neuronal cells may impair neuronal circuits and thus be a mechanism for causing psychiatric illness in these patients.

  17. Interaction between neuropeptide Y (NPY) and brain-derived neurotrophic factor in NPY-mediated neuroprotection against excitotoxicity: a role for microglia.

    Science.gov (United States)

    Xapelli, S; Bernardino, L; Ferreira, R; Grade, S; Silva, A P; Salgado, J R; Cavadas, C; Grouzmann, E; Poulsen, F R; Jakobsen, B; Oliveira, C R; Zimmer, J; Malva, J O

    2008-04-01

    The neuroprotective effect of neuropeptide Y (NPY) receptor activation was investigated in organotypic mouse hippocampal slice cultures exposed to the glutamate receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Exposure of 2-week-old slice cultures, derived from 7-day-old C57BL/6 mice, to 8 microm AMPA, for 24 h, induced degeneration of CA1 and CA3 pyramidal cells, as measured by cellular uptake of propidium iodide (PI). A significant neuroprotection, with a reduction of PI uptake in CA1 and CA3 pyramidal cell layers, was observed after incubation with a Y(2) receptor agonist [NPY(13-36), 300 nm]. This effect was sensitive to the presence of the selective Y(2) receptor antagonist (BIIE0246, 1 microm), but was not affected by addition of TrkB-Fc or by a neutralizing antibody against brain-derived neurotrophic factor (BDNF). Moreover, addition of a Y(1) receptor antagonist (BIBP3226, 1 microm) or a NPY-neutralizing antibody helped to disclose a neuroprotective role of endogenous NPY in CA1 region. Cultures exposed to 8 microm AMPA for 24 h, displayed, as measured by an enzyme-linked immunosorbent assay, a significant increase in BDNF. In such cultures there was an up-regulation of neuronal TrkB immunoreactivity, as well as the presence of BDNF-immunoreactive microglial cells at sites of injury. Thus, an increase of AMPA-receptor mediated neurodegeneration, in the mouse hippocampus, was prevented by neuroprotective pathways activated by NPY receptors (Y(1) and Y(2)), which can be affected by BDNF released by microglia and neurons.

  18. Our Faces in the Dog's Brain: Functional Imaging Reveals Temporal Cortex Activation during Perception of Human Faces.

    Science.gov (United States)

    Cuaya, Laura V; Hernández-Pérez, Raúl; Concha, Luis

    2016-01-01

    Dogs have a rich social relationship with humans. One fundamental aspect of it is how dogs pay close attention to human faces in order to guide their behavior, for example, by recognizing their owner and his/her emotional state using visual cues. It is well known that humans have specific brain regions for the processing of other human faces, yet it is unclear how dogs' brains process human faces. For this reason, our study focuses on describing the brain correlates of perception of human faces in dogs using functional magnetic resonance imaging (fMRI). We trained seven domestic dogs to remain awake, still and unrestrained inside an MRI scanner. We used a visual stimulation paradigm with block design to compare activity elicited by human faces against everyday objects. Brain activity related to the perception of faces changed significantly in several brain regions, but mainly in the bilateral temporal cortex. The opposite contrast (i.e., everyday objects against human faces) showed no significant brain activity change. The temporal cortex is part of the ventral visual pathway, and our results are consistent with reports in other species like primates and sheep, that suggest a high degree of evolutionary conservation of this pathway for face processing. This study introduces the temporal cortex as candidate to process human faces, a pillar of social cognition in dogs.

  19. Withania coagulans Extract Attenuates Histopathological Alteration and Apoptosis in Rat Brain Cortex Following Ischemia/Reperfusion Injury

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    Sarbishegi

    2016-01-01

    Full Text Available Background Cerebral ischemia and reperfusion (I/R is a pathological condition that arises by reduction or cessation in cerebral blood flow and return of oxygen and metabolites to brain cells, which cause oxidative damage. Objectives The aim of this study was to investigate the neuroprotective effects of Withania coagulans (WC extract on brain cortex in a rat model of I/R. Materials and Methods Thirty-two adult male Wistar rats weighing 280 - 300 g were used in this study. Animals were randomly divided to four groups (n = 8 as follow: sham operated group (I, I/R group (II, WCE500 + I/R (III and WCE1000 + I/R groups (IV. Pretreatment with WC extract (500, 1000 mg/kg was done by oral gavage for 30 days and global brain ischemia was induced by the common carotid occlusion for 30 minutes. After 72 hours, the animals were perfused transcardially and then the brains were prepared for histological study (H & E and TUNEL staining. Results The I/R group showed a significant increase in pycnotic (dying neurons and pretreatment with WC at doses of 500 mg/kg and 1000 mg/kg significantly reduced pycnotic and TUNEL positive neurons, in a dose dependent manner in ischemic brain cortex. Conclusions Our findings indicated that WC has neuroprotective effects and is able to reduce histopathological alterations and apoptosis in brain cortex I/R in rats.

  20. Collateralization of the pathways descending from the cerebral cortex to brain stem and spinal cord in cat and monkey

    NARCIS (Netherlands)

    K. Keizer (Koos)

    1989-01-01

    textabstractThe present study deals with the collateralization of the descending pathways from the cerebral cortex to the brain stem and the spinal cord in cat and monkey. The distributions of the branching cortical neurons were studied using retrograde fluorescent tracers. In addition, a new retrog

  1. Increased intrinsic brain connectivity between pons and somatosensory cortex during attacks of migraine with aura.

    Science.gov (United States)

    Hougaard, Anders; Amin, Faisal Mohammad; Larsson, Henrik B W; Rostrup, Egill; Ashina, Messoud

    2017-02-27

    The neurological disturbances of migraine aura are caused by transient cortical dysfunction due to waves of spreading depolarization that disrupt neuronal signaling. The effects of these cortical events on intrinsic brain connectivity during attacks of migraine aura have not previously been investigated. Studies of spontaneous migraine attacks are notoriously challenging due to their unpredictable nature and patient discomfort. We investigated 16 migraine patients with visual aura during attacks and in the attack-free state using resting state fMRI. We applied a hypothesis-driven seed-based approach focusing on cortical visual areas and areas involved in migraine pain, and a data-driven independent component analysis approach to detect changes in intrinsic brain signaling during attacks. In addition, we performed the analyses after mirroring the MRI data according to the side of perceived aura symptoms. We found a marked increase in connectivity during attacks between the left pons and the left primary somatosensory cortex including the head and face somatotopic areas (peak voxel: P = 0.0096, (x, y, z) = (-54, -32, 32), corresponding well with the majority of patients reporting right-sided pain. For aura-side normalized data, we found increased connectivity during attacks between visual area V5 and the lower middle frontal gyrus in the symptomatic hemisphere (peak voxel: P = 0.0194, (x, y, z) = (40, 40, 12). The present study provides evidence of altered intrinsic brain connectivity during attacks of migraine with aura, which may reflect consequences of cortical spreading depression, suggesting a link between aura and headache mechanisms. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  2. Cl- conduction of GABA(A)-receptor complex of synaptic membranes of rat brain cortex after development of chronic epileptization of the brain (pharmacological kindling).

    Science.gov (United States)

    Rebrov, I G; Karpova, M N; Andreev, A A; Klishina, N Y; Kalinina, M V; Kusnetzova, L V

    2008-03-01

    Experiments on Wistar rats showed that basal and muscimol-induced 36Cl- entry into synaptoneurosomes isolated from the brain cortex decreased after kindling (30 mg/kg pentylenetetrazole intraperitoneally for 30 days) in animals with seizure severity score 4-5. Changes in Cl- conduction during kindling are discussed.

  3. Diazepam-binding inhibitor. A brain neuropeptide present in human spinal fluid: studies in depression, schizophrenia, and Alzheimer's disease.

    Science.gov (United States)

    Barbaccia, M L; Costa, E; Ferrero, P; Guidotti, A; Roy, A; Sunderland, T; Pickar, D; Paul, S M; Goodwin, F K

    1986-12-01

    Diazepam-binding inhibitor is a novel peptide purified to homogeneity from rat and human brain. Diazepam-binding inhibitor is present, though not exclusively, in gamma-aminobutyric acid (GABA)-containing neurons where it is believed to inhibit GABAergic neurotransmission mediated by GABA by binding to the benzodiazepine-GABA receptor complex. Since an impairment of central GABAergic tone has been postulated to be associated with a number of neuropsychiatric disorders, we measured human diazepam-binding inhibitor immunoreactivity in the cerebrospinal fluid (CSF) of patients suffering from endogenous depression, schizophrenia, and dementia of the Alzheimer's type. Patients with major depression had significantly higher concentrations of human diazepam-binding inhibitor immunoreactivity in CSF when compared with age- and sex-matched normal volunteers, while no difference in CSF diazepam-binding inhibitor immunoreactivity was found in schizophrenics or patients with dementia of the Alzheimer's type when compared with controls. The possibility is discussed that the increased CSF human diazepam-binding inhibitor immunoreactivity observed in depressed patients may represent a functional disinhibition of GABAergic neurotransmission associated with depression.

  4. Interaction between neuropeptide Y (NPY) and brain-derived neurotrophic factor in NPY-mediated neuroprotection against excitotoxicity

    DEFF Research Database (Denmark)

    Xapelli, S; Bernardino, L; Ferreira, R;

    2008-01-01

    -day-old C57BL/6 mice, to 8 microm AMPA, for 24 h, induced degeneration of CA1 and CA3 pyramidal cells, as measured by cellular uptake of propidium iodide (PI). A significant neuroprotection, with a reduction of PI uptake in CA1 and CA3 pyramidal cell layers, was observed after incubation with a Y(2......) receptor agonist [NPY(13-36), 300 nm]. This effect was sensitive to the presence of the selective Y(2) receptor antagonist (BIIE0246, 1 microm), but was not affected by addition of TrkB-Fc or by a neutralizing antibody against brain-derived neurotrophic factor (BDNF). Moreover, addition of a Y(1) receptor...... antagonist (BIBP3226, 1 microm) or a NPY-neutralizing antibody helped to disclose a neuroprotective role of endogenous NPY in CA1 region. Cultures exposed to 8 microm AMPA for 24 h, displayed, as measured by an enzyme-linked immunosorbent assay, a significant increase in BDNF. In such cultures...

  5. Understanding the human parental brain: a critical role of the orbitofrontal cortex.

    Science.gov (United States)

    Parsons, Christine E; Stark, Eloise A; Young, Katherine S; Stein, Alan; Kringelbach, Morten L

    2013-01-01

    The bond between a parent and an infant often appears to form effortlessly and intuitively, and this relationship is fundamental to infant survival and development. Parenting is considered to depend on specific brain networks that are largely conserved across species and in place even before parenthood. Efforts to understand the neural basis of parenting in humans have focused on the overlapping networks implicated in reward and social cognition, within which the orbitofrontal cortex (OFC) is considered to be a crucial hub. This review examines emerging evidence that the OFC may be engaged in several phases of parent-infant interactions, from early, privileged orienting to infant cues, to ongoing monitoring of interactions and subsequent learning. Specifically, we review evidence suggesting that the OFC rapidly responds to a range of infant communicative cues, such as faces and voices, supporting their efficient processing. Crucially, this early orienting response may be fundamental in supporting adults to respond rapidly and appropriately to infant needs. We suggest a number of avenues for future research, including investigating neural activity in disrupted parenting, exploring multimodal cues, and consideration of neuroendocrine involvement in responsivity to infant cues. An increased understanding of the brain basis of caregiving will provide insight into our greatest challenge: parenting our young.

  6. Human umbilical cord blood cells restore brain damage induced changes in rat somatosensory cortex.

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    Maren Geissler

    Full Text Available Intraperitoneal transplantation of human umbilical cord blood (hUCB cells has been shown to reduce sensorimotor deficits after hypoxic ischemic brain injury in neonatal rats. However, the neuronal correlate of the functional recovery and how such a treatment enforces plastic remodelling at the level of neural processing remains elusive. Here we show by in-vivo recordings that hUCB cells have the capability of ameliorating the injury-related impairment of neural processing in primary somatosensory cortex. Intact cortical processing depends on a delicate balance of inhibitory and excitatory transmission, which is disturbed after injury. We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored. Additionally, the lesion induced hyperexcitability was no longer observed in hUCB treated animals as indicated by a paired-pulse behaviour resembling that observed in control animals. The beneficial effects on cortical processing were reflected in an almost complete recovery of sensorimotor behaviour. Our results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. We propose that the intermediate level of cortical processing will become relevant as a new stage to investigate efficacy and mechanisms of cell therapy in the treatment of brain injury.

  7. THE EFFECT OF UNFAVOURABLE FACTORS ON PERUVATE KINASE ACTIVITY IN BRAIN CORTEX OF WHITE RATS IN POSTNATAL ONTOGENESIS

    Directory of Open Access Journals (Sweden)

    L. M. Guseynova

    2012-12-01

    Full Text Available The effect of unionizated electromagnetic radiation (EMI of different intensity and hypoxia on pyruvate kinase activity (PK; EC 2.7.1.40 in the tissues of right and left hemispheres of white rats has been studied during postnatal ontogenesis. The highest hyperactivity of PK was revealed in the left hemisphere of brain cortex both in the control animals and after the influence of extremal environmental factors. It was stated that hypoxia induces higher changes in the dynamics of changes in the dynamics of changes in the PK-activity in the tissues of brain cortex than EMI, which leads to changes in energy supply of brain. The changes in the PK-activity are supposed to be caused by involving decay products and activation of biosynthetic processes into energy supply of cells.

  8. Analysis of neural activity in human motor cortex -- Towards brain machine interface system

    Science.gov (United States)

    Secundo, Lavi

    The discovery of directional tuned neurons in the primary motor cortex has advanced motor research in several domains. For instance, in the area of brain machine interface (BMI), researchers have exploited the robust characteristic of tuned motor neurons to allow monkeys to learn control of various machines. In the first chapter of this work we examine whether this phenomena can be observed using the less invasive method of recording electrocorticographic signals (ECoG) from the surface of a human's brain. Our findings reveal that individual ECoG channels contain complex movement information about the neuronal population. While some ECoG channels are tuned to hand movement direction (direction specific channels), others are associated to movement but do not contain information regarding movement direction (non-direction specific channels). More specifically, directionality can vary temporally and by frequency within one channel. In addition, a handful of channels contain no significant information regarding movement at all. These findings strongly suggest that directional and non-directional regions of cortex can be identified with ECoG and provide solutions to decoding movement at the signal resolution provided by ECoG. In the second chapter we examine the influence of movement context on movement reconstruction accuracy. We recorded neuronal signals recorded from electro-corticography (ECoG) during performance of cued- and self-initiated movements. ECoG signals were used to train a reconstruction algorithm to reconstruct continuous hand movement. We found that both cued- and self-initiated movements could be reconstructed with similar accuracy from the ECoG data. However, while an algorithm trained on the cued task could reconstruct performance on a subsequent cued trial, it failed to reconstruct self-initiated arm movement. The same task-specificity was observed when the algorithm was trained with self-initiated movement data and tested on the cued task. Thus

  9. Neuropeptides and obesity.

    Science.gov (United States)

    Beck, B

    2000-10-01

    This review focuses on the expression, content, and release of neuropeptides and on their role in the development of obesity in animal models with single-gene mutations. The balance between neuropeptides that contribute to the control of feeding behavior is profoundly and variously altered in these models, supporting the concept of the existence of several types of obesity. The hypothalamic neuropeptide Y (NPY) and the pro-opiomelanocortin (POMC) systems are the networks most studied in relation to energy intake. Both receive information about the nutritional status and the level of energy storage through insulin and leptin signaling mediated by specific receptors located on POMC and NPY neurons present predominantly in the arcuate nucleus (ARC). When leptin signaling is defective, through a defect in either the receptor (Zucker fa/fa rat, cp/cp rat, and db/db mouse) or in the peptide itself (ob/ob mouse), the NPY system is upregulated as shown by mRNA overexpression and increased peptide release, whereas the content and/or release of some inhibitory peptides (neurotensin, cholecystokinin) are diminished. For the POMC system, there is a complex interaction between the tonic inhibition of food intake exerted by alpha-melanocyte-stimulating hormone (alpha-MSH) and the Agouti-related protein at the level of the type 4 melanocortin receptor. The latter peptide is coexpressed with NPY in the ARC. Corticotropin-releasing factor (CRF) is the link between food intake and environmental factors. It not only inhibits food intake and prevents weight gain, likely through hypothalamic effects, but also activates the hypothalamo-pituitary axis and therefore contributes to energy storage in adipose tissue. The factors that prod the CRF system toward the hypothalamic or hypothalamo-pituitary axis system remain to be more clearly defined (comodulators, connections between limbic system and ARC, cellular location, and type of receptors, etc. ). The pathways used by all of these

  10. Neurological Change after Gamma Knife Radiosurgery for Brain Metastases Involving the Motor Cortex

    Science.gov (United States)

    Park, Chang-Yong; Choi, Hyun-Yong; Lee, Sang-Ryul; Roh, Tae Hoon; Seo, Mi-Ra

    2016-01-01

    Background Although Gamma Knife radiosurgery (GKRS) can provide beneficial therapeutic effects for patients with brain metastases, lesions involving the eloquent areas carry a higher risk of neurologic deterioration after treatment, compared to those located in the non-eloquent areas. We aimed to investigate neurological change of the patients with brain metastases involving the motor cortex (MC) and the relevant factors related to neurological deterioration after GKRS. Methods We retrospectively reviewed clinical, radiological and dosimetry data of 51 patients who underwent GKRS for 60 brain metastases involving the MC. Prior to GKRS, motor deficits existed in 26 patients (50.9%). The mean target volume was 3.2 cc (range 0.001–14.1) at the time of GKRS, and the mean prescription dose was 18.6 Gy (range 12–24 Gy). Results The actuarial median survival time from GKRS was 19.2±5.0 months. The calculated local tumor control rates at 6 and 12 months after GKRS were 89.7% and 77.4%, respectively. During the median clinical follow-up duration of 12.3±2.6 months (range 1–54 months), 18 patients (35.3%) experienced new or worsened neurologic deficits with a median onset time of 2.5±0.5 months (range 0.3–9.7 months) after GKRS. Among various factors, prescription dose (>20 Gy) was a significant factor for the new or worsened neurologic deficits in univariate (p=0.027) and multivariate (p=0.034) analysis. The managements of 18 patients were steroid medication (n=10), boost radiation therapy (n=5), and surgery (n=3), and neurological improvement was achieved in 9 (50.0%). Conclusion In our series, prescription dose (>20 Gy) was significantly related to neurological deterioration after GKRS for brain metastases involving the MC. Therefore, we suggest that careful dose adjustment would be required for lesions involving the MC to avoid neurological deterioration requiring additional treatment in the patients with limited life expectancy. PMID:27867921

  11. Neuropeptides and hippocampal neurogenesis.

    Science.gov (United States)

    Zaben, M J; Gray, W P

    2013-12-01

    Hippocampal neurogenesis is important for modulating the behavioural responses to stress and for certain forms of learning and memory. The mechanisms underlying the necessary coupling of neuronal activity to neural stem/progenitor cell (NSPC) function remain poorly understood. Within the dentate subgranular stem cell niche, local interneurons appear to play an important part in this excitation-neurogenesis coupling via GABAergic transmission, which promotes neuronal differentiation and integration. Neuropeptides such as neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) and galanin have emerged as important mediators for signalling local and extrinsic interneuronal activity to subgranular zone precursors. Here we review the distribution of these neuropeptides and their receptors in the neurogenic area of the hippocampus and their precise effects on hippocampal neurogenesis. We also discuss neuropeptides' potential involvement in functional aspects of hippocampal neurogenesis particularly their involvement in the modulation of learning and memory and behavior responses.

  12. Exploratory metabolomic analyses reveal compounds correlated with lutein concentration in frontal cortex, hippocampus, and occipital cortex of human infant brain

    Science.gov (United States)

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with...

  13. Neuropeptide physiology in helminths.

    Science.gov (United States)

    Mousley, Angela; Novozhilova, Ekaterina; Kimber, Michael J; Day, Tim A

    2010-01-01

    Parasitic worms come from two distinct, distant phyla, Nematoda (roundworms) and Platyhelminthes (flatworms). The nervous systems of worms from both phyla are replete with neuropeptides and there is ample physiological evidence that these neuropeptides control vital aspects of worm biology. In each phyla, the physiological evidence for critical roles for helminth neuropeptides is derived from both parasitic and free-living members. In the nematodes, the intestinal parasite Ascaris suum and the free-living Caenorhabditis elegans have yielded most of the data; in the platyhelminths, the most physiological data has come from the blood fluke Schistosoma mansoni. FMRFamide-like peptides (FLPs) have many varied effects (excitation, relaxation, or a combination) on somatic musculature, reproductive musculature, the pharynx and motor neurons in nematodes. Insulin-like peptides (INSs) play an essential role in nematode dauer formation and other developmental processes. There is also some evidence for a role in somatic muscle control for the somewhat heterogeneous grouping ofpeptides known as neuropeptide-like proteins (NLPs). In platyhelminths, as in nematodes, FLPs have a central role in somatic muscle function. Reports of FLP physiological action in platyhelminths are limited to a potent excitation of the somatic musculature. Platyhelminths are also abundantly endowed with neuropeptide Fs (NPFs), which appear absent from nematodes. There is not yet any data linking platyhelminth NPF to any particular physiological outcome, but this neuropeptide does potently and specifically inhibit cAMP accumulation in schistosomes. In nematodes and platyhelminths, there is an abundance of physiological evidence demonstrating that neuropeptides play critical roles in the biology of both free-living and parasitic helminths. While it is certainly true that there remains a great deal to learn about the biology of neuropeptides in both phyla, physiological evidence presently available points

  14. Deep brain stimulation in the lateral orbitofrontal cortex impairs spatial reversal learning.

    Science.gov (United States)

    Klanker, Marianne; Post, Ger; Joosten, Ruud; Feenstra, Matthijs; Denys, Damiaan

    2013-05-15

    Deep Brain Stimulation (DBS) is a successful novel treatment for treatment-resistant obsessive-compulsive disorder and is currently under investigation for addiction and eating disorders. Clinical and preclinical studies have shown functional changes in the orbitofrontal cortex (OFC) following DBS in the ventral capsule/ventral striatum. These findings suggest that DBS can affect neural activity in distant regions that are connected to the site of electrode implantation. However, the behavioral consequences of direct OFC stimulation are not known. Here, we studied the effects of direct stimulation in the lateral OFC on spatial discrimination and reversal learning in rats. Rats were implanted with stimulating electrodes and were trained on a spatial discrimination and reversal learning task. DBS in the OFC did not affect acquisition of a spatial discrimination. Stimulated animals made more incorrect responses during the first reversal. Acquisition of the second reversal was not affected. These results suggest that DBS may inhibit activity in the OFC, or may disrupt output of the OFC to other cortical or subcortical areas, resulting in perseverative behavior or an inability to adapt behavior to altered response-reward contingencies.

  15. Cerebellum and motor learning, motor memory and motor integration: morphology and distribution of neuropeptide Y neurons in rat cerebellar cortex%大鼠小脑皮质内神经肽Y能神经元的形态与分布小脑的运动学习、记忆及整合功能

    Institute of Scientific and Technical Information of China (English)

    王省; 孙银平; 蔡新华

    2005-01-01

    BACKGROUND: Neuropeptide Y (NPY) neurons are extensively located in various brain regions such as cerebral cortex, caudate-putamen nucleus, syslimbic system, thalamus and brain stem. They are also involved in various brain activities such as motor learning, motor memory and motor integration. Considering the fact that cerebellum can reorganize through motor learning, we tried to identify the morphology and distribution of NPY neurons in rat's cerebellar cortex to obtain the morphologic knowledge that is related to its cerebellar-cortex-based motor learning.OBJECTIVE: To investigate the morphology and distribution of NPY -immunoreactive neurons in rat's cerebellar cortex, and discuss the relationship between NPY neurons and cerebellum motor learning and motor memory.DESIGN: A single-sample-study based on animal samples.SETTING: Anatomy Department, Pathophysiology Department and Morphology Center in Xinxiang Medical College.MATERIALS: From July to December 2001, the experiment was performed at the Morphology Center in Xinxiang Medical College. Ten Sprague-Dawley (SD) rats, clean grade, regardless of their gender and weighing 100-200 g,were selected.METHODS: After intraperitoneal injection anesthesia and ascending aorta infusion fixation, the cerebellum was taken out by craniosurgery. The cerebellum was immersed in the same fixative fluid for duration of 48 hours, and then was embedded in paraffin. The next step was to make continuous sagittal sections. NPY neurons were identified by SP immunohistochemical staining, using rats cerebral section as the positive control. In the negative control, the first antibody replaced by Bovine Calf Serum(BCS), and the second antibody replaced by 0.01 mol/L PBS. Sequentially the light-microscopic observation and micrography were recorded.MAIN OUTCOME MEASUREMENTS: The Morphology and distribution of NPY neurons in rat's cerebellar cortex were taken as main outcome measurements.RESULTS: NPY-immunoreactive neurons were distributed in

  16. Penultimate proline in neuropeptides.

    Science.gov (United States)

    Glover, Matthew S; Bellinger, Earl P; Radivojac, Predrag; Clemmer, David E

    2015-08-18

    A recent ion mobility spectrometry-mass spectrometry (IMS-MS) study revealed that tryptic peptide ions containing a proline residue at the second position from the N-terminus (i.e., penultimate proline) frequently adopt multiple conformations, owing to the cis-trans isomerization of Xaa(1)-Pro(2) peptide bonds [J. Am. Soc. Mass Spectrom. 2015, 26, 444]. Here, we present a statistical analysis of a neuropeptide database that illustrates penultimate proline residues are frequently found in neuropeptides. In order to probe the effect of penultimate proline on neuropeptide conformations, IMS-MS experiments were performed on two model peptides in which penultimate proline residues were known to be important for biological activity: the N-terminal region of human neuropeptide Y (NPY1-9, Tyr(1)-Pro(2)-Ser(3)-Lys(4)-Pro(5)-Asp(6)-Asn(7)-Pro(8)-Gly(9)-NH2) and a tachykinin-related peptide (CabTRP Ia, Ala(1)-Pro(2)-Ser(3)-Gly(4)-Phe(5)-Leu(6)-Gly(7)-Met(8)-Arg(9)-NH2). From these studies, it appears that penultimate prolines allow neuropeptides to populate multiple conformations arising from the cis-trans isomerization of Xaa(1)-Pro(2) peptide bonds. Although it is commonly proposed that the role of penultimate proline residues is to protect peptides from enzymatic degradation, the present results indicate that penultimate proline residues also are an important means of increasing the conformational heterogeneity of neuropeptides.

  17. Oxytocin in the medial prefrontal cortex regulates maternal care, maternal aggression and anxiety during the postpartum period

    OpenAIRE

    2014-01-01

    The neuropeptide oxytocin (OT) acts on a widespread network of brain regions to regulate numerous behavioral adaptations during the postpartum period including maternal care, maternal aggression, and anxiety. In the present study, we examined whether this network also includes the medial prefrontal cortex (mPFC). We found that bilateral infusion of a highly specific oxytocin receptor antagonist (OTR-A) into the prelimbic (PL) region of the mPFC increased anxiety-like behavior in postpartum, b...

  18. Oxytocin in the medial prefrontal cortex is involved in maternal care, maternal aggression and anxiolysis during the postpartum period

    OpenAIRE

    2014-01-01

    The neuropeptide oxytocin (OT) acts on a widespread network of brain regions to regulate numerous behavioral adaptations during the postpartum period including maternal care, maternal aggression, and anxiolysis. In the present study, we examined whether this network also includes the medial prefrontal cortex (mPFC). We found that bilateral infusion of a highly specific oxytocin receptor antagonist (OTR-A) into the prelimbic (PL) region of the mPFC increased anxiety-like behavior in postpartum...

  19. Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers.

    Science.gov (United States)

    Marques-Aleixo, I; Santos-Alves, E; Balça, M M; Rizo-Roca, D; Moreira, P I; Oliveira, P J; Magalhães, J; Ascensão, A

    2015-08-20

    We here investigate the effects of two exercise modalities (endurance treadmill training-TM and voluntary free-wheel activity-FW) on the brain cortex and cerebellum mitochondrial bioenergetics, permeability transition pore (mPTP), oxidative stress, as well as on proteins involved in mitochondrial biogenesis, apoptosis, and quality control. Eighteen male rats were assigned to sedentary-SED, TM and FW groups. Behavioral alterations and ex vivo brain mitochondrial function endpoints were assessed. Proteins involved in oxidative phosphorylation (OXPHOS, including the adenine nucleotide translocator), oxidative stress markers and regulatory proteins (SIRT3, p66shc, UCP2, carbonyls, MDA, -SH, aconitase, Mn-SOD), as well as proteins involved in mitochondrial biogenesis (PGC1α, TFAM) were evaluated. Apoptotic signaling was measured through quantifying caspase 3, 8 and 9-like activities, Bax, Bcl2, CypD, and cofilin expression. Mitochondrial dynamics (Mfn1/2, OPA1 and DRP1) and auto(mito)phagy (LC3II, Beclin1, Pink1, Parkin, p62)-related proteins were also measured by Western blotting. Only the TM exercise group showed increased spontaneous alternation and exploratory activity. Both exercise regimens improved mitochondrial respiratory activity, increased OXPHOS complexes I, III and V subunits in both brain subareas and decreased oxidative stress markers. Increased resistance to mPTP and decreased apoptotic signaling were observed in the brain cortex from TM and in the cerebellum from TM and FW groups. Also, exercise increased the expression of proteins involved in mitochondrial biogenesis, autophagy and fusion, simultaneous with decreased expression of mitochondrial fission-related protein DRP1. In conclusion, physical exercise improves brain cortex and cerebellum mitochondrial function, decreasing oxidative stress and apoptotic related markers. It is also possible that favorable alterations in mitochondrial biogenesis, dynamics and autophagy signaling induced by exercise

  20. Alpha II Spectrin breakdown products in immature Sprague Dawley rat hippocampus and cortex after traumatic brain injury.

    Science.gov (United States)

    Schober, Michelle E; Requena, Daniela F; Davis, Lizeth J; Metzger, Ryan R; Bennett, Kimberly S; Morita, Denise; Niedzwecki, Christian; Yang, Zhihui; Wang, Kevin K W

    2014-07-29

    After traumatic brain injury (TBI), proteolysis of Alpha II Spectrin by Calpain 1 produces 145 Spectrin breakdown products (SBDPs) while proteolysis by Caspase 3 produces 120 SBDPs. 145 and 120 SBDP immunoblotting reflects the relative importance of caspase-dependent apoptosis or calpain-dependent excitotoxic/necrotoxic cell death in brain regions over time. In the adult rat, controlled cortical impact (CCI) increased 120 SBDPs in the first hours, lasting a few days, and increased 145 SBDPs within the first few days lasting up to 14 days after injury. Little is known about SBDPs in the immature brain after TBI. Since development affects susceptibility to apoptosis after TBI, we hypothesized that CCI would increase 145 and 120 SBDPs in the immature rat brain relative to SHAM during the first 3 and 5 days, respectively. SBDPs were measured in hippocampi and cortices at post injury days (PID) 1, 2, 3, 5, 7 and 14 after CCI or SHAM surgery in the 17 day old Sprague Dawley rat. 145 SBDPs increased in both brain tissues ipsilateral to injury during the first 3 days, while changes in contralateral tissues were limited to PID2 cortex. 145 SBDPs elevations were more marked and enduring in hippocampus than in cortex. Against expectations, 120 SBDPs only increased in PID1 hippocampus and PID2 cortex. 145 SBDPs elevations occurred early after CCI, similar to previous studies in the adult rat, but resolved more quickly. The minimal changes in 120 SBDPs suggest that calpain-dependent, but not caspase-dependent, cell death predominates in the 17 day old rat after CCI. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Neuropeptides as targets for the development of anticonvulsant drugs.

    Science.gov (United States)

    Clynen, Elke; Swijsen, Ann; Raijmakers, Marjolein; Hoogland, Govert; Rigo, Jean-Michel

    2014-10-01

    Epilepsy is a common neurological disorder characterized by recurrent seizures. These seizures are due to abnormal excessive and synchronous neuronal activity in the brain caused by a disruption of the delicate balance between excitation and inhibition. Neuropeptides can contribute to such misbalance by modulating the effect of classical excitatory and inhibitory neurotransmitters. In this review, we discuss 21 different neuropeptides that have been linked to seizure disorders. These neuropeptides show an aberrant expression and/or release in animal seizure models and/or epilepsy patients. Many of these endogenous peptides, like adrenocorticotropic hormone, angiotensin, cholecystokinin, cortistatin, dynorphin, galanin, ghrelin, neuropeptide Y, neurotensin, somatostatin, and thyrotropin-releasing hormone, are able to suppress seizures in the brain. Other neuropeptides, such as arginine-vasopressine peptide, corticotropin-releasing hormone, enkephalin, β-endorphin, pituitary adenylate cyclase-activating polypeptide, and tachykinins have proconvulsive properties. For oxytocin and melanin-concentrating hormone both pro- and anticonvulsive effects have been reported, and this seems to be dose or time dependent. All these neuropeptides and their receptors are interesting targets for the development of new antiepileptic drugs. Other neuropeptides such as nesfatin-1 and vasoactive intestinal peptide have been less studied in this field; however, as nesfatin-1 levels change over the course of epilepsy, this can be considered as an interesting marker to diagnose patients who have suffered a recent epileptic seizure.

  2. Inhibition of noradrenaline release in the rat brain cortex via presynaptic H3 receptors.

    Science.gov (United States)

    Schlicker, E; Fink, K; Hinterthaner, M; Göthert, M

    1989-12-01

    The effects of histamine and related drugs on the evoked tritium overflow from superfused rat brain cortex slices preincubated with 3H-noradrenaline were determined. Tritium overflow was stimulated electrically (3 Hz; slices superfused with normal physiological salt solution) or by introduction of CaCl2 1.3 mmol/l (slices superfused with Ca2(+)-free medium containing K+ 20 mmol/l). Histamine slightly decreased the electrically evoked 3H overflow in slices superfused in the presence of desipramine. The degree of inhibition obtained with histamine was doubled when both desipramine and phentolamine were present in the superfusion medium (pIC15 6.46). Under the latter condition, the evoked overflow was inhibited by the H3 receptor agonist R-(-)-alpha-methylhistamine and its S-(+) enantiomer (pIC15 7.36 and 5.09, respectively), but was not affected by the H2 receptor agonist dimaprit and the H1 receptor agonist 2-thiazolylethylamine (both at up to 32 mumols/l). The concentration-response curve of histamine was shifted to the right by the H3 receptor antagonists thioperamide, impromidine and burimamide (apparent pA2 8.37, 6.86 and 7.05, respectively), by the H2 receptor antagonist ranitidine (apparent pA2 4.27) and was not affected by the H1 receptor antagonist dimetindene (32 mumols/l). The inhibitory effect of R-(-)-alpha-methylhistamine on the evoked overflow was also counteracted by thioperamide. Given alone, none of the five histamine receptor antagonists affected the evoked overflow. In the absence of desipramine plus phentolamine, impromidine and burimamide facilitated the electrically evoked 3H overflow whereas thioperamide had no effect. The facilitatory effects of impromidine and burimamide were abolished by phentolamine, but not affected by desipramine.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Distinct proteins in cortex of rats with closed traumatic brain injury detected by a WCX-2 protein chip

    Institute of Scientific and Technical Information of China (English)

    Li Zhan; Lin Liang; Qingming Shu; Shuwang Yang; Yongliang Zhang

    2007-01-01

    BACKGROUND: Mechanical injury can cause the changes of polygene expression spectrum in rat cerebral cortical nerve cells, and then result in the changes of intracellular protein expression. At present, dielectrophoresis is combined with mass spectrum technique to detect the expression of different proteins in rat cortex after brain injury, but the protein chip technique requires further investigation. OBJECTIVE: To analyze the differences of protein expression spectrum in rat cerebral cortex before and after closed traumatic brain injury using WCX-2 protein chip technique. DESIGN: A randomized controlled animal experiment.SETTING: Training Division of the Medical College of Chinese People's Armed Police Force. MATERIALS: Seventy-two male SD rats of clean degree, 350 - 450 g, were provided by the Experimental Animal Center, Academy of Military Medical Sciences of Chinese PLA. Urea, trifluoroacetic acid, CHAPS and Tris (Sigma, USA); WCX-2 (Ciphergen, USA). Ultra-high speed hypothermia centrifuger (Bechman, USA); Rotary tissue microtome (Keuca, Germany); Biochip processor and PBS II-C protein chip reader (Ciphergen, USA).METHODS: The experiments were carried out in the Institute of Molecular Pathology, Central Laboratory, and Department of Pathology, Medical College of Chinese People's Armed Police Force from June 2005 to March 2006.①Grouping and treatment: The experiments were completed in molecular pathological institute, central laboratory and pathological department.①The rats were randomly divided into control group (n =12) and brain injury group (n =60). Marmarou's weight-dropping models were duplicated at different time points in the brain injury group. In the control group, the rats were only treated by incising the skin of head top, without fixing the stainless steel hitting backup plate at the vault of skull, and obtain brain cortex for pathological and protein chip research, and they were killed after 24 hours. The rats in the brain injury group were

  4. Pattern of chondroitin sulfate proteoglycan expression after ablation of the sensorimotor cortex of the neonatal and adult rat brain

    Directory of Open Access Journals (Sweden)

    Dacić Sanja

    2008-01-01

    Full Text Available The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs. In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment.

  5. Hypocretin and nicotine excite the same thalamocortical synapses in prefrontal cortex: correlation with improved attention in rat.

    Science.gov (United States)

    Lambe, Evelyn K; Olausson, Peter; Horst, Nicole K; Taylor, Jane R; Aghajanian, George K

    2005-05-25

    Thalamic projections to prefrontal cortex are important for executive aspects of attention. Using two-photon imaging in prefrontal brain slices, we show that nicotine and the wakefulness neuropeptide hypocretin (orexin) excite the same identified synapses of the thalamocortical arousal pathway within the prefrontal cortex. Although it is known that attention can be improved when nicotine is infused directly into the midlayer of the prefrontal cortex in the rat, the effects of hypocretin on attention are not known. The overlap in thalamocortical synapses excited by hypocretin and nicotine and the lack of direct postsynaptic effects prompted us to compare their effects on a sustained and divided attention task in the rat. Similar to nicotine, infusions of hypocretin-2 peptide into the prefrontal cortex significantly improved accuracy under high attentional demand without effects on other performance measures. We show for the first time that hypocretin can improve attentional processes relevant to executive functions of the prefrontal cortex.

  6. Loss of entorhinal cortex and hippocampal volumes compared to whole brain volume in normal aging: the SMART-Medea study.

    Science.gov (United States)

    Knoops, Arnoud J G; Gerritsen, Lotte; van der Graaf, Yolanda; Mali, Willem P T M; Geerlings, Mirjam I

    2012-07-30

    In non-demented elderly age-related decline in hippocampal volume has often been observed, but it is not clear if this loss is disproportionate relative to other brain tissue. Few studies examined age-related volume loss of the entorhinal cortex. We investigated the association of age with hippocampal and entorhinal cortex (ERC) volumes in a large sample of middle-aged and older persons without dementia. Within the SMART-Medea study, cross-sectional analyses were performed in 453 non-demented subjects (mean age 62±9 years, 81% male) with a history of arterial disease. Hippocampal and ERC volumes were assessed by manual segmentation on three-dimensional fast field-echo sequence T1-weighted magnetic resonance images. Automated segmentation was used to quantify volumes of BV and ICV. Hippocampal and ERC volumes were divided by intracranial volume (ICV) as well as total brain volume (BV) to determine whether age-related differences were disproportionate relative to other brain tissue. Total crude hippocampal volume was 5.96±0.7 ml and total crude ERC volume was 0.34±0.06 ml. Linear regression analyses adjusted for sex showed that with increasing age, hippocampal volume divided by ICV decreased (B per year older=-0.01 ml; 95% CI -0.02 to -0.004). However, no age-related decline in hippocampal volume relative to BV was observed (B per year older=0.005 ml; 95% CI -0.002 to 0.01). No age-related decline in ERC volume relative to ICV or BV was observed. In this population of nondemented patients with a history of vascular disease no age-related decline in entorhinal cortex volume was observed and although hippocampal volume decreased with age, it was not disproportionate relative to total brain volume. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. The brain's code and its canonical computational motifs. From sensory cortex to the default mode network: A multi-scale model of brain function in health and disease.

    Science.gov (United States)

    Turkheimer, Federico E; Leech, Robert; Expert, Paul; Lord, Louis-David; Vernon, Anthony C

    2015-08-01

    A variety of anatomical and physiological evidence suggests that the brain performs computations using motifs that are repeated across species, brain areas, and modalities. The computational architecture of cortex, for example, is very similar from one area to another and the types, arrangements, and connections of cortical neurons are highly stereotyped. This supports the idea that each cortical area conducts calculations using similarly structured neuronal modules: what we term canonical computational motifs. In addition, the remarkable self-similarity of the brain observables at the micro-, meso- and macro-scale further suggests that these motifs are repeated at increasing spatial and temporal scales supporting brain activity from primary motor and sensory processing to higher-level behaviour and cognition. Here, we briefly review the biological bases of canonical brain circuits and the role of inhibitory interneurons in these computational elements. We then elucidate how canonical computational motifs can be repeated across spatial and temporal scales to build a multiplexing information system able to encode and transmit information of increasing complexity. We point to the similarities between the patterns of activation observed in primary sensory cortices by use of electrophysiology and those observed in large scale networks measured with fMRI. We then employ the canonical model of brain function to unify seemingly disparate evidence on the pathophysiology of schizophrenia in a single explanatory framework. We hypothesise that such a framework may also be extended to cover multiple brain disorders which are grounded in dysfunction of GABA interneurons and/or these computational motifs.

  8. The prefrontal cortex in the Göttingen minipig brain defined by neural projection criteria and cytoarchitecture

    DEFF Research Database (Denmark)

    Jelsing, J; Hay-Schmidt, Anders; Dyrby, Tim

    2006-01-01

    In an attempt to delineate the prefrontal cortex (PFC) in the Gottingen minipig brain the distribution of reciprocal thalamocortical projections was investigated using anterograde and retrograde tracing techniques and evaluated in relation to the specific cytoarchitectonic organization. Tracers...... were visualized using standard immunohistochemistry or evaluated in vivo using manganese (Mn2+) as an MRI paramagnetic tracer. The in vivo tract tracing turned out to be very sensitive with a high correspondence to the histological labelling. Tracers injected into the mediodorsal thalamus labelled...... connections to different parts of the MD nucleus. Although the granular layer IV, characteristic of primate PFC could not be identified, both cytoarchitectonic and connectional data suggests that the Gottingen minipig has a structurally divided prefrontal cortex. Stereological estimates of PFC volume showed...

  9. How Two Brains Make One Synchronized Mind in the Inferior Frontal Cortex: fNIRS-Based Hyperscanning During Cooperative Singing

    Science.gov (United States)

    Osaka, Naoyuki; Minamoto, Takehiro; Yaoi, Ken; Azuma, Miyuki; Shimada, Yohko Minamoto; Osaka, Mariko

    2015-01-01

    One form of communication that is common in all cultures is people singing together. Singing together reflects an index of cognitive synchronization and cooperation of human brains. Little is known about the neural synchronization mechanism, however. Here, we examined how two brains make one synchronized behavior using cooperated singing/humming between two people and hyperscanning, a new brain scanning technique. Hyperscanning allowed us to observe dynamic cooperation between interacting participants. We used functional near-infrared spectroscopy (fNIRS) to simultaneously record the brain activity of two people while they cooperatively sang or hummed a song in face-to-face (FtF) or face-to-wall (FtW) conditions. By calculating the inter-brain wavelet transform coherence between two interacting brains, we found a significant increase in the neural synchronization of the left inferior frontal cortex (IFC) for cooperative singing or humming regardless of FtF or FtW compared with singing or humming alone. On the other hand, the right IFC showed an increase in neural synchronization for humming only, possibly due to more dependence on musical processing. PMID:26635703

  10. Why does brain damage impair memory? A connectionist model of object recognition memory in perirhinal cortex.

    Science.gov (United States)

    Cowell, Rosemary A; Bussey, Timothy J; Saksida, Lisa M

    2006-11-22

    Object recognition is the canonical test of declarative memory, the type of memory putatively impaired after damage to the temporal lobes. Studies of object recognition memory have helped elucidate the anatomical structures involved in declarative memory, indicating a critical role for perirhinal cortex. We offer a mechanistic account of the effects of perirhinal cortex damage on object recognition memory, based on the assumption that perirhinal cortex stores representations of the conjunctions of visual features possessed by complex objects. Such representations are proposed to play an important role in memory when it is difficult to solve a task using representations of only individual visual features of stimuli, thought to be stored in regions of the ventral visual stream caudal to perirhinal cortex. The account is instantiated in a connectionist model, in which development of object representations with visual experience provides a mechanism for judgment of previous occurrence. We present simulations addressing the following empirical findings: (1) that impairments after damage to perirhinal cortex (modeled by removing the "perirhinal cortex" layer of the network) are exacerbated by lengthening the delay between presentation of to-be-remembered items and test, (2) that such impairments are also exacerbated by lengthening the list of to-be-remembered items, and (3) that impairments are revealed only when stimuli are trial unique rather than repeatedly presented. This study shows that it may be possible to account for object recognition impairments after damage to perirhinal cortex within a hierarchical, representational framework, in which complex conjunctive representations in perirhinal cortex play a critical role.

  11. Neuropeptides in cnidarians

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, Cornelis J.P.; Williamson, Michael; Hansen, Georg Nørgaard

    2002-01-01

    Cnidarians are the lowest animal group having a nervous system. In the primitive nervous systems of cnidarians, peptides play important roles as neurotransmitters or neurohormones. So far, we have isolated and sequenced about 35 neuropeptides from different cnidarian classes (Hydrozoa, Scyphozoa,...

  12. Neuropeptides in cardiovascular control.

    Science.gov (United States)

    Ganong, W F

    1984-12-01

    Neuropeptides can affect cardiovascular function in various ways. They can serve as cotransmitters in the autonomic nervous system; for example, vasoactive intestinal peptide (VIP) is released with acetylcholine and neuropeptide Y with norepinephrine from postganglionic neurons. Substance P and, presumably, other peptides can can affect cardiovascular function when released near blood vessels by antidromically conducted impulses in branches of stimulated sensory neurons. In the central nervous system, many different neuropeptides appear to function as transmitters or contransmittes in the neural pathways that regulate the cardiovascular system. In addition neuropeptides such as vasopressin and angiotensin II also circulate as hormones that are involved in cardiovascular control. Large doses of exogenous vasopressin are required to increase blood pressure in normal animals because the increase in total peripheral resistance produced by the hormones is accompanied by a decrease in cardiac output. However, studies with synthetic peptides that selectively antagonize the vasopressor action of vasopressin indicate that circulating vasopressin is important in maintaining blood pressure when animals are hypovolemic due to dehydration, haemorrhage or adrenocortical insufficiency. VIP dilates blood vessels and stimulates renin secretion by a direct action on the juxtaglomerular cells. Renin secretion is stimulated when the concentration of VIP in plasma exceeds 75 pmol/litre, and higher values are seen in a number of conditions. Neostigmine, a drug which increases the secretion of endogenous VIP, also increases renin secretion, and this increase is not blocked by renal denervation or propranolol. Thus, VIP may be a physiologically significant renin stimulating hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain

    Directory of Open Access Journals (Sweden)

    Andrea Forero

    2017-09-01

    Full Text Available Background: During early prenatal stages of brain development, serotonin (5-HT-specific neurons migrate through somal translocation to form the raphe nuclei and subsequently begin to project to their target regions. The rostral cluster of cells, comprising the median and dorsal raphe (DR, innervates anterior regions of the brain, including the prefrontal cortex. Differential analysis of the mouse 5-HT system transcriptome identified enrichment of cell adhesion molecules in 5-HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13 has been shown to play a role in cell migration, axon pathfinding, and synaptogenesis. This study aimed to investigate the contribution of Cdh13 to the development of the murine brain 5-HT system.Methods: For detection of Cdh13 and components of the 5-HT system at different embryonic developmental stages of the mouse brain, we employed immunofluorescence protocols and imaging techniques, including epifluorescence, confocal and structured illumination microscopy. The consequence of CDH13 loss-of-function mutations on brain 5-HT system development was explored in a mouse model of Cdh13 deficiency.Results: Our data show that in murine embryonic brain Cdh13 is strongly expressed on 5-HT specific neurons of the DR and in radial glial cells (RGCs, which are critically involved in regulation of neuronal migration. We observed that 5-HT neurons are intertwined with these RGCs, suggesting that these neurons undergo RGC-guided migration. Cdh13 is present at points of intersection between these two cell types. Compared to wildtype controls, Cdh13-deficient mice display increased cell densities in the DR at embryonic stages E13.5, E17.5, and adulthood, and higher serotonergic innervation of the prefrontal cortex at E17.5.Conclusion: Our findings provide evidence for a role of CDH13 in the development of the serotonergic system in early embryonic stages. Specifically, we indicate that Cdh13 deficiency affects the cell

  14. Immunohistochemical localization of the neuropeptide S receptor in the rat central nervous system.

    Science.gov (United States)

    Leonard, S K; Ring, R H

    2011-01-13

    The neuropeptide S receptor (NPSR) is a G-protein coupled receptor that is potently activated by the linear 20 amino acid peptide, neuropeptide S (NPS). Central administration of NPS promotes arousal and anxiolytic-like effects in rodents, and fails to promote such effects in NPSR knockout animals or in the presence of NPSR-selective antagonists. In situ hybridization (ISH) studies in rat brain have revealed that the mRNAs encoding the NPS precursor and the NPS receptor are expressed at high levels in discrete regions of the rat CNS. The distribution of the NPSR protein in brain has not been reported due to a lack of available antibodies. We have generated and validated a NPSR-specific antibody and used it to determine the distribution of the NPSR in male Sprague-Dawley (SD) rat brain. The anti-NPSR antibody identified a single protein by Western blot with an estimated molecular weight of 65 kD, which was prevented by pre-incubation of the antibody with the immunizing peptide. The protein distribution identified with this antibody in rat brain was consistent both with the mRNA distribution identified by in situ hybridization, and to the localization pattern identified by a second NPSR-specific antibody against a distinct NPSR epitope. NPSR protein was identified in the medial amygdala (MeA), substantia nigra pars compacta, subiculum, dorsal raphe, and several hypothalamic and thalamic regions. Additionally, NPSR protein was localized in the pyramidal cell layer of the ventral hippocampus, the medial habenula (MHb), and was widely distributed in the cortex. The distribution of NPSR protein provides further insight into the organization of the NPS system and may guide future studies on the role of the NPSR in brain.

  15. Advances in Mass Spectrometric Tools for Probing Neuropeptides

    Science.gov (United States)

    Buchberger, Amanda; Yu, Qing; Li, Lingjun

    2015-07-01

    Neuropeptides are important mediators in the functionality of the brain and other neurological organs. Because neuropeptides exist in a wide range of concentrations, appropriate characterization methods are needed to provide dynamic, chemical, and spatial information. Mass spectrometry and compatible tools have been a popular choice in analyzing neuropeptides. There have been several advances and challenges, both of which are the focus of this review. Discussions range from sample collection to bioinformatic tools, although avenues such as quantitation and imaging are included. Further development of the presented methods for neuropeptidomic mass spectrometric analysis is inevitable, which will lead to a further understanding of the complex interplay of neuropeptides and other signaling molecules in the nervous system.

  16. Deconstructing the brain's moral network: dissociable functionality between the temporoparietal junction and ventro-medial prefrontal cortex.

    Science.gov (United States)

    Feldmanhall, Oriel; Mobbs, Dean; Dalgleish, Tim

    2014-03-01

    Research has illustrated that the brain regions implicated in moral cognition comprise a robust and broadly distributed network. However, understanding how these brain regions interact and give rise to the complex interplay of cognitive processes underpinning human moral cognition is still in its infancy. We used functional magnetic resonance imaging to examine patterns of activation for 'difficult' and 'easy' moral decisions relative to matched non-moral comparators. This revealed an activation pattern consistent with a relative functional double dissociation between the temporoparietal junction (TPJ) and ventro-medial prefrontal cortex (vmPFC). Difficult moral decisions activated bilateral TPJ and deactivated the vmPFC and OFC. In contrast, easy moral decisions revealed patterns of activation in the vmPFC and deactivation in bilateral TPJ and dorsolateral PFC. Together these results suggest that moral cognition is a dynamic process implemented by a distributed network that involves interacting, yet functionally dissociable networks.

  17. Neuropeptides controlling energy balance: orexins and neuromedins.

    Science.gov (United States)

    Nixon, Joshua P; Kotz, Catherine M; Novak, Colleen M; Billington, Charles J; Teske, Jennifer A

    2012-01-01

    In this chapter, we review the feeding and energy expenditure effects of orexin (also known as hypocretin) and neuromedin. Orexins are multifunctional neuropeptides that affect energy balance by participating in regulation of appetite, arousal, and spontaneous physical activity. Central orexin signaling for all functions originates in the lateral hypothalamus-perifornical area and is likely functionally differentiated based on site of action and on interacting neural influences. The effect of orexin on feeding is likely related to arousal in some ways but is nonetheless a separate neural process that depends on interactions with other feeding-related neuropeptides. In a pattern distinct from other neuropeptides, orexin stimulates both feeding and energy expenditure. Orexin increases in energy expenditure are mainly by increasing spontaneous physical activity, and this energy expenditure effect is more potent than the effect on feeding. Global orexin manipulations, such as in transgenic models, produce energy balance changes consistent with a dominant energy expenditure effect of orexin. Neuromedins are gut-brain peptides that reduce appetite. There are gut sources of neuromedin, but likely the key appetite-related neuromedin-producing neurons are in the hypothalamus and parallel other key anorectic neuropeptide expression in the arcuate to paraventricular hypothalamic projection. As with other hypothalamic feeding-related peptides, hindbrain sites are likely also important sources and targets of neuromedin anorectic action. Neuromedin increases physical activity in addition to reducing appetite, thus producing a consistent negative energy balance effect. Together with the other various neuropeptides, neurotransmitters, neuromodulators, and neurohormones, neuromedin and orexin act in the appetite network to produce changes in food intake and energy expenditure, which ultimately influences the regulation of body weight.

  18. Coordinated gene expression of neuroinflammatory and cell signaling markers in dorsolateral prefrontal cortex during human brain development and aging.

    Directory of Open Access Journals (Sweden)

    Christopher T Primiani

    Full Text Available BACKGROUND: Age changes in expression of inflammatory, synaptic, and neurotrophic genes are not well characterized during human brain development and senescence. Knowing these changes may elucidate structural, metabolic, and functional brain processes over the lifespan, as well vulnerability to neurodevelopmental or neurodegenerative diseases. HYPOTHESIS: Expression levels of inflammatory, synaptic, and neurotrophic genes in the human brain are coordinated over the lifespan and underlie changes in phenotypic networks or cascades. METHODS: We used a large-scale microarray dataset from human prefrontal cortex, BrainCloud, to quantify age changes over the lifespan, divided into Development (0 to 21 years, 87 brains and Aging (22 to 78 years, 144 brains intervals, in transcription levels of 39 genes. RESULTS: Gene expression levels followed different trajectories over the lifespan. Many changes were intercorrelated within three similar groups or clusters of genes during both Development and Aging, despite different roles of the gene products in the two intervals. During Development, changes were related to reported neuronal loss, dendritic growth and pruning, and microglial events; TLR4, IL1R1, NFKB1, MOBP, PLA2G4A, and PTGS2 expression increased in the first years of life, while expression of synaptic genes GAP43 and DBN1 decreased, before reaching plateaus. During Aging, expression was upregulated for potentially pro-inflammatory genes such as NFKB1, TRAF6, TLR4, IL1R1, TSPO, and GFAP, but downregulated for neurotrophic and synaptic integrity genes such as BDNF, NGF, PDGFA, SYN, and DBN1. CONCLUSIONS: Coordinated changes in gene transcription cascades underlie changes in synaptic, neurotrophic, and inflammatory phenotypic networks during brain Development and Aging. Early postnatal expression changes relate to neuronal, glial, and myelin growth and synaptic pruning events, while late Aging is associated with pro-inflammatory and synaptic loss

  19. Metabolism of Cryptic Peptides Derived from Neuropeptide FF Precursors: The Involvement of Insulin-Degrading Enzyme

    Directory of Open Access Journals (Sweden)

    Giuseppe Grasso

    2014-09-01

    Full Text Available The term “cryptome” refers to the subset of cryptic peptides with bioactivities that are often unpredictable and very different from the parent protein. These cryptic peptides are generated by proteolytic cleavage of proteases, whose identification in vivo can be very challenging. In this work, we show that insulin-degrading enzyme (IDE is able to degrade specific amino acid sequences present in the neuropeptide pro-NPFFA (NPFF precursor, generating some cryptic peptides that are also observed after incubation with rat brain cortex homogenate. The reported experimental findings support the increasingly accredited hypothesis, according to which, due to its wide substrate selectivity, IDE is involved in a wide variety of physiopathological processes.

  20. Orphan neuropeptides. Novel neuropeptides modulating sleep or feeding.

    Science.gov (United States)

    Chung, Shinjae; Civelli, Olivier

    2006-08-01

    Neuropeptides form the largest family of modulators of synaptic transmission. Until 1995 some 60 different neuropeptides had been found. With the recognition that all neuropeptides act by binding to G protein coupled receptors (GPCRs), a new approach relying on the use of orphan GPCRs as targets was designed to identify novel neuropeptides. Thirteen new neuropeptide families have since been discovered. In this review we will describe the orphan GPCR-based approach that led to these discoveries and present its impact on two specific physiological responses, feeding and sleep. In particular, we will discuss the modulatory roles of the hypocretins/orexins and of neuropeptide S in sleep and awakening and those of ghrelin and melanin concentrating hormone in food intake.

  1. Decreased levels of pNR1 S897 protein in the cortex of neonatal Sprague Dawley rats with hypoxic-ischemic or NMDA-induced brain damage

    Energy Technology Data Exchange (ETDEWEB)

    Hei, Ming-Yan; Tao, Hui-Kang; Tang, Qin; Yu, Bo; Zhao, Ling-Ling [Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan (China)

    2012-06-22

    Our objective was to investigate the protein level of phosphorylated N-methyl-D-aspartate (NMDA) receptor-1 at serine 897 (pNR1 S897) in both NMDA-induced brain damage and hypoxic-ischemic brain damage (HIBD), and to obtain further evidence that HIBD in the cortex is related to NMDA toxicity due to a change of the pNR1 S897 protein level. At postnatal day 7, male and female Sprague-Dawley rats (13.12 ± 0.34 g) were randomly divided into normal control, phosphate-buffered saline (PBS) cerebral microinjection, HIBD, and NMDA cerebral microinjection groups. Immunofluorescence and Western blot (N = 10 rats per group) were used to examine the protein level of pNR1 S897. Immunofluorescence showed that control and PBS groups exhibited significant neuronal cytoplasmic staining for pNR1 S897 in the cortex. Both HIBD and NMDA-induced brain damage markedly decreased pNR1 S897 staining in the ipsilateral cortex, but not in the contralateral cortex. Western blot analysis showed that at 2 and 24 h after HIBD, the protein level of pNR1 S897 was not affected in the contralateral cortex (P > 0.05), whereas it was reduced in the ipsilateral cortex (P < 0.05). At 2 h after NMDA injection, the protein level of pNR1 S897 in the contralateral cortex was also not affected (P > 0.05). The levels in the ipsilateral cortex were decreased, but the change was not significant (P > 0.05). The similar reduction in the protein level of pNR1 S897 following both HIBD and NMDA-induced brain damage suggests that HIBD is to some extent related to NMDA toxicity possibly through NR1 phosphorylation of serine 897.

  2. Electrical impedance of mouse brain cortex in vitro from 4.7 kHz to 2.0 MHz.

    Science.gov (United States)

    Wilson, M T; Elbohouty, M; Voss, L J; Steyn-Ross, D A

    2014-02-01

    The electrical impedance of samples of mouse brain cortex has been measured between 4.7 kHz and 2.0 MHz. Brain slices of thickness 400 μm were prepared from two mice. Each slice was placed in either normal artificial cerebrospinal fluid or magnesium-free artificial cerebrospinal fluid; the latter induces seizure-like electrical behaviour. A total of 74 samples of cortex of approximate size 2 mm × 2 mm were then cut from these slices. Each sample in turn was placed between two flat Ag/AgCl electrodes and electrical impedance measured with an Agilent E4980A four-point impedance monitor. The measurements showed two regions of significant dispersion. Circuits based on the Cole-Cole and Fricke models, consisting of inductive, nonlinear capacitive and resistive elements were used to model the behaviour. Distributions of values for each circuit element have been determined for the samples prepared in seizing and non-seizing conditions. Few differences were found between the values of circuit elements between the seizing and non-seizing groups.

  3. Intermittent hypoxia stimulates formation of binuclear neurons in brain cortex- a role of cell fusion in neuroprotection?

    Science.gov (United States)

    Paltsyn, Alexander A; Manukhina, Eugenia B; Goryacheva, Anna V; Downey, H Fred; Dubrovin, Ivan P; Komissarova, Svetlana V; Kubatiev, Aslan A

    2014-05-01

    Oligodendrocyte fusion with neurons in the brain cortex is a part of normal ontogenesis and is a possible means of neuroregeneration. Following such fusion, the oligodendrocyte nucleus undergoes neuron-specific reprogramming, resulting in the formation of binuclear neurons, which doubles the functional capability of the neuron. In this study, we tested the hypothesis that the formation of binuclear neurons is involved in long-term adaptation of the brain to intermittent hypobaric hypoxia, which is known to be neuroprotective. Rats were adapted to hypoxia in an altitude chamber at a simulated altitude of 4000 m above sea level for 14 days (30 min increasing to 4 h, daily). One micrometer sections of the left motor cortex were analyzed by light microscopy. Phases of the fusion and reprogramming process were recorded, and the number of binuclear neurons was counted for all section areas containing pyramidal neurons of layers III-V. For the control group subjected to sham hypoxia, the density of binuclear neurons was 4.49 ± 0.32 mm(2). In the hypoxia-adapted group, this density increased to 5.71 ± 0.39 mm(2) (P neurons did not differ from the number observed in the control group. We suggest that the increased content of binuclear neurons may serve as a structural basis for the neuroprotective effects of the adaptation to hypoxia.

  4. Dietary flavonoid fisetin regulates aluminium chloride-induced neuronal apoptosis in cortex and hippocampus of mice brain.

    Science.gov (United States)

    Prakash, Dharmalingam; Sudhandiran, Ganapasam

    2015-12-01

    Dietary flavonoids have been suggested to promote brain health by protecting brain parenchymal cells. Recently, understanding the possible mechanism underlying neuroprotective efficacy of flavonoids is of great interest. Given that fisetin exerts neuroprotection, we have examined the mechanisms underlying fisetin in regulating Aβ aggregation and neuronal apoptosis induced by aluminium chloride (AlCl3) administration in vivo. Male Swiss albino mice were induced orally with AlCl3 (200 mg/kg. b.wt./day/8 weeks). Fisetin (15 mg/Kg. b.wt. orally) was administered for 4 weeks before AlCl3-induction and administered simultaneously for 8 weeks during AlCl3-induction. We found aggregation of Amyloid beta (Aβ 40-42), elevated expressions of Apoptosis stimulating kinase (ASK-1), p-JNK (c-Jun N-terminal Kinase), p53, cytochrome c, caspases-9 and 3, with altered Bax/Bcl-2 ratio in favour of apoptosis in cortex and hippocampus of AlCl3-administered mice. Furthermore, TUNEL and fluoro-jade C staining demonstrate neurodegeneration in cortex and hippocampus. Notably, treatment with fisetin significantly (Pfisetin treatment. We have identified the involvement of fisetin in regulating ASK-1 and p-JNK as possible mediator of Aβ aggregation and subsequent neuronal apoptosis during AlCl3-induced neurodegeneration. These findings define the possibility that fisetin may slow or prevent neurodegneration and can be utilised as neuroprotective agent against Alzheimer's and Parkinson's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Higher Brain Functions Served by the Lowly Rodent Primary Visual Cortex

    Science.gov (United States)

    Gavornik, Jeffrey P.; Bear, Mark F.

    2014-01-01

    It has been more than 50 years since the first description of ocular dominance plasticity--the profound modification of primary visual cortex (V1) following temporary monocular deprivation. This discovery immediately attracted the intense interest of neurobiologists focused on the general question of how experience and deprivation modify the brain…

  6. Higher Brain Functions Served by the Lowly Rodent Primary Visual Cortex

    Science.gov (United States)

    Gavornik, Jeffrey P.; Bear, Mark F.

    2014-01-01

    It has been more than 50 years since the first description of ocular dominance plasticity--the profound modification of primary visual cortex (V1) following temporary monocular deprivation. This discovery immediately attracted the intense interest of neurobiologists focused on the general question of how experience and deprivation modify the brain…

  7. Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum

    Science.gov (United States)

    Azmitia, E. C.; Saccomano, Z. T.; Alzoobaee, M. F.; Boldrini, M.; Whitaker-Azmitia, P. M.

    2016-01-01

    In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was…

  8. Using Complexity Measure to Characterize Information Transmission of Human Brain Cortex

    Institute of Scientific and Technical Information of China (English)

    徐京华; 吴祥宝

    1994-01-01

    The information transmission among various parts of the cortex are computed with the the-ory of mutual information from the data of the electroencephalogram(EEG)time series of normal humansubjects.The intensities of these transmissions are characterized by the"complexity"measures.These mea-sures have revealed to be sensitively related to the functional conditions of human beings.

  9. Brain-derived neurotrophic factor, phosphorylated cyclic AMP response element binding protein and neuropeptide Y decline as early as middle age in the dentate gyrus and CA1 and CA3 subfields of the hippocampus.

    Science.gov (United States)

    Hattiangady, Bharathi; Rao, Muddanna S; Shetty, Geetha A; Shetty, Ashok K

    2005-10-01

    The hippocampus is very susceptible to aging. Severely diminished dentate neurogenesis at middle age is one of the most conspicuous early changes in the aging hippocampus, which is likely linked to an early decline in the concentration of neurotrophic factors and signaling proteins that influence neurogenesis. We analyzed three proteins that are well-known to promote dentate neurogenesis and learning and memory function in the dentate gyrus and the hippocampal CA1 and CA3 subfields of young, middle-aged and aged F344 rats. These include the brain-derived neurotrophic factor (BDNF), the transcription factor phosphorylated cyclic AMP response element binding protein (p-CREB) and the neuropeptide neuropeptide Y (NPY). The BDNF was analyzed via ELISA and BDNF immunohistochemistry, the p-CREB through densitometric analysis of p-CREB immunopositive cells, and the NPY via stereological counting of NPY-immunopositive interneurons. We provide new evidence that the BDNF concentration, the p-CREB immunoreactivity and the number of NPY immunopositive interneurons decline considerably by middle age in both dentate gyrus and CA1 and CA3 subfields of the hippocampus. However, both BDNF concentration and NPY immunopositive interneuron numbers exhibit no significant decrease between middle age and old age. In contrast, the p-CREB immunoreactivity diminishes further during this period, which is also associated with reduced BDNF immunoreaction within the soma of dentate granule cells and hippocampal pyramidal neurons. Collectively, these results suggest that severely dampened dentate neurogenesis observed at middle age is linked at least partially to reduced concentrations of BDNF, p-CREB and NPY, as each of these proteins is a positive regulator of dentate neurogenesis. Dramatically diminished CREB phosphorylation (and persistently reduced levels of BDNF and NPY) at old age may underlie the learning and memory impairments observed during senescence.

  10. Neuropeptides in learning and memory.

    Science.gov (United States)

    Borbély, Eva; Scheich, Bálint; Helyes, Zsuzsanna

    2013-12-01

    Dementia conditions and memory deficits of different origins (vascular, metabolic and primary neurodegenerative such as Alzheimer's and Parkinson's diseases) are getting more common and greater clinical problems recently in the aging population. Since the presently available cognitive enhancers have very limited therapeutical applications, there is an emerging need to elucidate the complex pathophysiological mechanisms, identify key mediators and novel targets for future drug development. Neuropeptides are widely distributed in brain regions responsible for learning and memory processes with special emphasis on the hippocampus, amygdala and the basal forebrain. They form networks with each other, and also have complex interactions with the cholinergic, glutamatergic, dopaminergic and GABA-ergic pathways. This review summarizes the extensive experimental data in the well-established rat and mouse models, as well as the few clinical results regarding the expression and the roles of the tachykinin system, somatostatin and the closely related cortistatin, vasoactive intestinal polypeptide (VIP) and pituitary adenylate-cyclase activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), opioid peptides and galanin. Furthermore, the main receptorial targets, mechanisms and interactions are described in order to highlight the possible therapeutical potentials. Agents not only symptomatically improving the functional impairments, but also inhibiting the progression of the neurodegenerative processes would be breakthroughs in this area. The most promising mechanisms determined at the level of exploratory investigations in animal models of cognitive disfunctions are somatostatin sst4, NPY Y2, PACAP-VIP VPAC1, tachykinin NK3 and galanin GALR2 receptor agonisms, as well as delta opioid receptor antagonism. Potent and selective non-peptide ligands with good CNS penetration are needed for further characterization of these molecular pathways to

  11. Positive selection in ASPM is correlated with cerebral cortex evolution across primates but not with whole-brain size.

    Science.gov (United States)

    Ali, Farhan; Meier, Rudolf

    2008-11-01

    The rapid increase of brain size is a key event in human evolution. Abnormal spindle-like microcephaly associated (ASPM) is discussed as a major candidate gene for explaining the exceptionally large brain in humans but ASPM's role remains controversial. Here we use codon-specific models and a comparative approach to test this candidate gene that was initially identified in Homo-chimp comparisons. We demonstrate that accelerated evolution of ASPM (omega = 4.7) at 16 amino acid sites occurred in 9 primate lineages with major changes in relative cerebral cortex size. However, ASPM's evolution is not correlated with major changes in relative whole-brain or cerebellum sizes. Our results suggest that a single candidate gene such as ASPM can influence a specific component of the brain across large clades through changes in a few amino acid sites. We furthermore illustrate the power of using continuous phenotypic variability across primates to rigorously test candidate genes that have been implicated in the evolution of key human traits.

  12. Brain banks as key part of biochemical and molecular studies on cerebral cortex involvement in Parkinson's disease.

    Science.gov (United States)

    Ravid, Rivka; Ferrer, Isidro

    2012-04-01

    Exciting developments in basic and clinical neuroscience and recent progress in the field of Parkinson's disease (PD) are partly a result of the availability of human specimens obtained through brain banks. These banks have optimized the methodological, managerial and organizational procedures; standard operating procedures; and ethical, legal and social issues, including the code of conduct for 21st Century brain banking and novel protocols. The present minireview focuses on current brain banking organization and management, as well as the likely future direction of the brain banking field. We emphasize the potentials and pitfalls when using high-quality specimens of the human central nervous system for advancing PD research. PD is a generalized disease in which α-synuclein is not a unique component but, instead, is only one of the players accounting for the complex impairment of biochemical/molecular processes involved in metabolic pathways. This is particularly important in the cerebral cortex, where altered cognition has a complex neurochemical substrate. Mitochondria and energy metabolism impairment, abnormal RNA, microRNA, protein synthesis, post-translational protein modifications and alterations in the lipid composition of membranes and lipid rafts are part of these complementary factors. We have to be alert to the possible pitfalls of each specimen and its suitability for a particular study. Not all samples qualify for the study of DNA, RNA, proteins, post-translational modifications, lipids and metabolomes, although the use of carefully selected samples and appropriate methods minimizes pitfalls and errors and guarantees high-quality reserach.

  13. Experimental study on alteration of adrenergic receptors activity in neuronal membranes protein of cerebral cortex following brain trauma in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xin-wei; XU Ru-xiang; QI Yi-long; CHEN Chang-cai

    2001-01-01

    Objective: To define the course of changes taken by α1 and β adrenergic receptors (AR) activity after traumatic brain injury (TBI) and explore the approach for secondary brain injury (SBI) management. Methods: The neuronal membrane protein of cortex were extracted from the rats subject to traumatic brain injury, and the changes of α1- and β-AR activities in the neuronal membranes were examined by radio ligand binding assay (RLBA). Results: α1- and β-AR activities underwent obvious changes, reaching their peak values at 24 h after TBI. α1-AR binding density (Bmax) reduced by 22.6%while the ligand affinity increased by 66.7%, and for β-AR, however, Bmax increased by 116.9% and the ligand affinity reduced by 50.7%. Their antagonists could counteract the changes ofα1- and β-AR activity. Conclusion: The patterns of changes varies between α1- and β-AR activity after TBI, suggesting their different roles in the neuronal membranes after brain trauma, and timely administration of AR antagonists is potentially beneficial in TBI management.

  14. Role of neuropeptides in cardiomyopathies.

    Science.gov (United States)

    Dvorakova, Magdalena Chottova; Kruzliak, Peter; Rabkin, Simon W

    2014-11-01

    The role of neuropeptides in cardiomyopathy-associated heart failure has been garnering more attention. Several neuropeptides--Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP) and their receptors have been studied in the various types of cardiomyopathies. The data indicate associations with the strength of the association varying depending on the kind of neuropeptide and the nature of the cardiomyopathy--diabetic, ischemic, inflammatory, stress-induced or restrictive cardiomyopathy. Several neuropeptides appear to alter regulation of genes involved in heart failure. Demonstration of an association is an essential first step in proving causality or establishing a role for a factor in a disease. Understanding the complexity of neuropeptide function should be helpful in establishing new or optimal therapeutic strategies for the treatment of heart failure in cardiomyopathies.

  15. Altered expression of neuropeptides in FoxG1-null heterozygous mutant mice.

    Science.gov (United States)

    Frullanti, Elisa; Amabile, Sonia; Lolli, Maria Grazia; Bartolini, Anna; Livide, Gabriella; Landucci, Elisa; Mari, Francesca; Vaccarino, Flora M; Ariani, Francesca; Massimino, Luca; Renieri, Alessandra; Meloni, Ilaria

    2016-02-01

    Foxg1 gene encodes for a transcription factor essential for telencephalon development in the embryonic mammalian forebrain. Its complete absence is embryonic lethal while Foxg1 heterozygous mice are viable but display microcephaly, altered hippocampal neurogenesis and behavioral and cognitive deficiencies. In order to evaluate the effects of Foxg1 alteration in adult brain, we performed expression profiling in total brains from Foxg1+/- heterozygous mutants and wild-type littermates. We identified statistically significant differences in expression levels for 466 transcripts (Pneuropeptides have an important role in maternal and social behavior, and their alteration is associated with impaired social interaction and autistic behavior. In addition, Neuronatin (Nnat) levels appear significantly higher both in Foxg1+/- whole brain and in hippocampal neurons after silencing Foxg1, strongly suggesting that it is directly or indirectly repressed by Foxg1. During fetal and neonatal brain development, Nnat may regulate neuronal excitability, receptor trafficking and calcium-dependent signaling and, in the adult brain, it is predominantly expressed in parvalbumin-positive GABAergic interneurons. Overall, these results implicate the overexpression of a group of neuropeptides in the basal ganglia, hypothalamus, cortex and hippocampus in the pathogenesis FOXG1 behavioral impairments.

  16. A Cognição Social e o Córtex Cerebral Social Cognition and the Brain Cortex

    Directory of Open Access Journals (Sweden)

    Judith Butman

    2001-01-01

    Full Text Available A cognição social é o processo que orienta condutas frente a outros indivíduos da mesma espécie. Várias estruturas cerebrais têm um papel chave para controlar as condutas sociais: o córtex pré-frontal ventromedial, a amígdala, o córtex somatosensorial direito e a ínsula. O córtex pré-frontal ventromedial está comprometido com o raciocínio social e com a tomada de decisões; a amígdala com o julgamento social de faces; o córtex somatosensorial direito, com a empatia e com a simulação; enquanto que a insula, com a resposta autonômica. Estes achados estão de acordo com a hipótese do marcador somático, um mecanismo específico por meio do qual adquirimos, representamos ou memorizamos os valores de nossas ações. Estas estruturas cerebrais atuam como mediadores entre as representações perceptuais dos estímulos sensoriais e a recuperação do conhecimento que o estímulo pode ativar. O sistema límbico é a zona limítrofe; nela, a psicologia se encontra com a neurologia. A correta sincronização destas zonas e estruturas, no adulto, é a chave para uma situação livre de patologia.Social cognition refers to the processes that subserve behavior in response to other individuals of the same species. Several brain structures play a key role in guiding social behaviors: ventromedial prefrontal cortex, amygdala, right somatosensory cortex and insula. The ventromedial prefrontal cortex is most directly involved in social reasoning and decision making; the amygdala in social judgment of faces, the right somatosensory cortex in empathy and simulation and the insula in autonomic responses. These findings are corresponding to the somatic marker hypothesis, particular mechanism by which we acquire, represent and retrieve the values of our actions. These brain structures appear to mediate between perceptual representation of social stimuli and retrieval of knowledge that such stimuli can trigger. The limbic system is the border zone

  17. Decreased levels of pNR1 S897 protein in the cortex of neonatal Sprague Dawley rats with hypoxic-ischemic or NMDA-induced brain damage

    Directory of Open Access Journals (Sweden)

    Ming-Yan Hei

    2012-10-01

    Full Text Available Our objective was to investigate the protein level of phosphorylated N-methyl-D-aspartate (NMDA receptor-1 at serine 897 (pNR1 S897 in both NMDA-induced brain damage and hypoxic-ischemic brain damage (HIBD, and to obtain further evidence that HIBD in the cortex is related to NMDA toxicity due to a change of the pNR1 S897 protein level. At postnatal day 7, male and female Sprague Dawley rats (13.12 ± 0.34 g were randomly divided into normal control, phosphate-buffered saline (PBS cerebral microinjection, HIBD, and NMDA cerebral microinjection groups. Immunofluorescence and Western blot (N = 10 rats per group were used to examine the protein level of pNR1 S897. Immunofluorescence showed that control and PBS groups exhibited significant neuronal cytoplasmic staining for pNR1 S897 in the cortex. Both HIBD and NMDA-induced brain damage markedly decreased pNR1 S897 staining in the ipsilateral cortex, but not in the contralateral cortex. Western blot analysis showed that at 2 and 24 h after HIBD, the protein level of pNR1 S897 was not affected in the contralateral cortex (P > 0.05, whereas it was reduced in the ipsilateral cortex (P 0.05. The levels in the ipsilateral cortex were decreased, but the change was not significant (P > 0.05. The similar reduction in the protein level of pNR1 S897 following both HIBD and NMDA-induced brain damage suggests that HIBD is to some extent related to NMDA toxicity possibly through NR1 phosphorylation of serine 897.

  18. Cross-generational trans fat intake facilitates mania-like behavior: oxidative and molecular markers in brain cortex.

    Science.gov (United States)

    Trevizol, F; Roversi, Kr; Dias, V T; Roversi, K; Barcelos, R C S; Kuhn, F T; Pase, C S; Golombieski, R; Veit, J C; Piccolo, J; Pochmann, D; Porciúncula, L O; Emanuelli, T; Rocha, J B T; Bürger, M E

    2015-02-12

    Since that fast food consumption have raised concerns about people's health, we evaluated the influence of trans fat consumption on behavioral, biochemical and molecular changes in the brain-cortex of second generation rats exposed to a model of mania. Two successive generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy, lactation to adulthood, when male rats from 2nd generation received amphetamine (AMPH-4 mg/kg-i.p., once a day, for 14 days) treatment. AMPH increased locomotor index in all animals, which was higher in the HVF group. While the FO group showed increased n-3 polyunsaturated fatty acid (PUFA) incorporation and reduced n-6/n-3 PUFA ratio, HVF allowed trans fatty acid (TFA) incorporation and increased n-6/n-3 PUFA ratio in the brain-cortex. In fact, the FO group showed minor AMPH-induced hyperactivity, decreased reactive species (RS) generation per se, causing no changes in protein carbonyl (PC) levels and dopamine transporter (DAT). FO supplementation showed molecular changes, since proBDNF was increased per se and reduced by AMPH, decreasing the brain-derived neurotrophic factor (BDNF) level following drug treatment. Conversely, HVF was related to increased hyperactivity, higher PC level per se and higher AMPH-induced PC level, reflecting on DAT, whose levels were decreased per se as well as in AMPH-treated groups. In addition, while HVF increased BDNF-mRNA per se, AMPH reduced this value, acting on BDNF, whose level was lower in the same AMPH-treated experimental group. ProBDNF level was influenced by HVF supplementation, but it was not sufficient to modify BDNF level. These findings reinforce that prolonged consumption of trans fat allows TFA incorporation in the cortex, facilitating hyperactive behavior, oxidative damages and molecular changes. Our study is a warning about cross-generational consumption

  19. Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety.

    Science.gov (United States)

    Dolcos, Sanda; Hu, Yifan; Iordan, Alexandru D; Moore, Matthew; Dolcos, Florin

    2016-02-01

    Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain-personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  20. Stepwise Connectivity of the Modal Cortex Reveals the Multimodal Organization of the Human Brain

    Science.gov (United States)

    Sepulcre, Jorge; Sabuncu, Mert R.; Yeo, Thomas B.; Liu, Hesheng; Johnson, Keith A.

    2012-01-01

    How human beings integrate information from external sources and internal cognition to produce a coherent experience is still not well understood. During the past decades, anatomical, neurophysiological and neuroimaging research in multimodal integration have stood out in the effort to understand the perceptual binding properties of the brain. Areas in the human lateral occipito-temporal, prefrontal and posterior parietal cortices have been associated with sensory multimodal processing. Even though this, rather patchy, organization of brain regions gives us a glimpse of the perceptual convergence, the articulation of the flow of information from modality-related to the more parallel cognitive processing systems remains elusive. Using a method called Stepwise Functional Connectivity analysis, the present study analyzes the functional connectome and transitions from primary sensory cortices to higher-order brain systems. We identify the large-scale multimodal integration network and essential connectivity axes for perceptual integration in the human brain. PMID:22855814

  1. Association of medial prefrontal cortex connectivity with consciousness level and its outcome in patients with acquired brain injury.

    Science.gov (United States)

    Liu, Xiaoyan; Li, Jingqi; Gao, Jian; Zhou, Zhen; Meng, Fanxia; Pan, Gang; Luo, Benyan

    2017-08-01

    Medial prefrontal cortex (mPFC) is usually known for participating in virtually all self related processing. However, few have investigated the role of mPFC in modulating conscious awareness. This study aimed to depict the relationship between the mPFC connectivity and the severity and outcome of the disorders of consciousness (DOC) among patients with acquired brain injury. Thirty-four patients with DOC (17 in a minimally conscious state and 17 in an unresponsive wakefulness syndrome/vegetative state) and 11 healthy controls were recruited, underwent clinical assessment and resting-state functional MRI scan, and were further followed up to evaluate recovery outcome using the Glasgow Outcome Scale. The mPFC connectivity was then analyzed, by comparing DOC patients to healthy controls at baseline, and by comparing "recovered consciousness" and "non-recovered consciousness" patients at follow-up, as identified by graph theory. As a result, enhanced mPFC connectivity against weakened posteromedial cortex connectivity was observed in a minimally conscious state, not in an unresponsive wakefulness syndrome/vegetative state. Besides, increased mPFC connectivity was significantly associated with consciousness recovery. In conclusion, the mPFC connectivity could possibly serve as a mark to track the severity and outcome of DOC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Changes of Brain Connectivity in the Primary Motor Cortex After Subcortical Stroke: A Multimodal Magnetic Resonance Imaging Study.

    Science.gov (United States)

    Li, Yongxin; Wang, Defeng; Zhang, Heye; Wang, Ya; Wu, Ping; Zhang, Hongwu; Yang, Yang; Huang, Wenhua

    2016-02-01

    The authors investigated the changes in connectivity networks of the bilateral primary motor cortex (M1) of subcortical stroke patients using a multimodal neuroimaging approach with antiplatelet therapy. Nineteen patients were scanned at 2 time points: before and 1 month after the treatment. The authors assessed the resting-state functional connectivity (FC) and probabilistic fiber tracking of left and right M1 of every patient, and then compared these results to the 15 healthy controls. The authors also evaluated the correlations between the neuroimaging results and clinical scores.Compared with the controls, the patients showed a significant decrease of FC in the contralateral motor cortex before treatment, and the disrupted FC was restored after treatment. The fiber tracking results in the controls indicated that the body of the corpus callosum should be the main pathway connecting the M1 and contralateral hemispheres. All patients exhibited reduced probability of structural connectivity within this pathway before treatment and which was restored after treatment. Significant correlations were also found in these patients between the connectivity results and clinical scores, which might imply that the connectivity of M1 can be used to evaluate the motor skills in stroke patients.These findings can help elucidate the neural mechanisms responsible for the brain connectivity recovery after stroke.

  3. Is Spreading Depolarization Characterized by an Abrupt, Massive Release of Gibbs Free Energy from the Human Brain Cortex?

    Science.gov (United States)

    Dreier, Jens P.; Isele, Thomas; Reiffurth, Clemens; Offenhauser, Nikolas; Kirov, Sergei A.; Dahlem, Markus A.; Herreras, Oscar

    2012-01-01

    In the evolution of the cerebral cortex, the sophisticated organization in a steady state far away from thermodynamic equilibrium has produced the side effect of two fundamental pathological network events: ictal epileptic activity and spreading depolarization. Ictal epileptic activity describes the partial disruption, and spreading depolarization describes the near-complete disruption of the physiological double Gibbs–Donnan steady state. The occurrence of ictal epileptic activity in patients has been known for decades. Recently, unequivocal electrophysiological evidence has been found in patients that spreading depolarizations occur abundantly in stroke and brain trauma. The authors propose that the ion changes can be taken to estimate relative changes in Gibbs free energy from state to state. The calculations suggest that in transitions from the physiological state to ictal epileptic activity to spreading depolarization to death, the cortex releases Gibbs free energy in a stepwise fashion. Spreading depolarization thus appears as a twilight state close to death. Consistently, electrocorticographic recordings in the core of focal ischemia or after cardiac arrest display a smooth transition from the initial spreading depolarization component to the later ultraslow negative potential, which is assumed to reflect processes in cellular death. PMID:22829393

  4. Functionally Brain Network Connected to the Retrosplenial Cortex of Rats Revealed by 7T fMRI.

    Science.gov (United States)

    Wang, Jingjuan; Nie, Binbin; Duan, Shaofeng; Zhu, Haitao; Liu, Hua; Shan, Baoci

    2016-01-01

    Functional networks are regarded as important mechanisms for increasing our understanding of brain function in healthy and diseased states, and increased interest has been focused on extending the study of functional networks to animal models because such models provide a functional understanding of disease progression, therapy and repair. In rodents, the retrosplenial cortex (RSC) is an important cortical region because it has a large size and presents transitional patterns of lamination between the neocortex and archicortex. In addition, a number of invasive studies have highlighted the importance of the RSC for many functions. However, the network based on the RSC in rodents remains unclear. Based on the critical importance of the RSC, we defined the bilateral RSCs as two regions of interest and estimated the network based on the RSC. The results showed that the related regions include the parietal association cortex, hippocampus, thalamus nucleus, midbrain structures, and hypothalamic mammillary bodies. Our findings indicate two possible major networks: a sensory-cognitive network that has a hub in the RSCs and processes sensory information, spatial learning, and episodic memory; and a second network that is involved in the regulation of visceral functions and arousal. In addition, functional asymmetry between the bilateral RSCs was observed.

  5. Electrical activity of the visual cortex under conditions of change in the levels of monoamines in the brain of animals.

    Science.gov (United States)

    Borob'ev, V V; Gal'chenko, A A; Deryugina, O N

    1991-01-01

    The changes in the electrograms of the visual cortex of awake animals under the influence of light stimulation in conditions of a pharmacological effect on the monoamine (MA) systems of the brain were investigated in experiments on 8 rabbits and 12 rats. The following was found following the administration of MA precursors (5-hydroxytryptophan and d,l-dihydroxyphenylalanine): a) a decrease in the amplitude of the averaged evoked potentials in response to rhythmical light stimuli (1-20 pulses/sec); b) intensification of rapid (15-25 Hz) oscillations in the spontaneous electrical activity of the cortex, as well as attenuation and modification of the effects of the blocker of MA synthesis, a-methyl-dihydroxyphenylalanine. A potentiation of the MA precursors was observed with light stimulation in the frequency spectra of the electrocorticograms. The specific characteristics of the action of the catecholamine precursor were manifested in the same conditions in the form of an intensification of the power of the 5-7 Hz rhythms, and an attenuation of the power of the 2-3 Hz rhythms.

  6. Deep brain stimulation versus motor cortex stimulation for neuropathic pain: A minireview of the literature and proposal for future research.

    Science.gov (United States)

    Honey, C Michael; Tronnier, Volker M; Honey, Christopher R

    2016-01-01

    The treatment of neuropathic pain remains a public health concern. A growing cohort of patients is plagued by medically refractory, unrelenting severe neuropathic pain that ruins their quality of life and productivity. For this group, neurosurgery can offer two different kinds of neuromodulation that may help: deep brain simulation (DBS) and motor cortex stimulation (MCS). Unfortunately, there is no consensus on how to perform these procedures, which stimulation parameters to select, how to measure success, and which patients may benefit. This brief review highlights the literature supporting each technique and attempts to provide some comparisons and contrasts between DBS and MCS for the treatment of neuropathic pain. Finally, we highlight the current unanswered questions in the field and suggest future research strategies that may advance the care of our patients with neuropathic pain.

  7. [Electrical activity of the visual cortex under conditions of altered monoamine levels in the brain of animals].

    Science.gov (United States)

    Vorob'ev, V V; Gal'chenko, A A; Deriugina, O N

    1990-01-01

    In experiments on 8 rabbits and 12 rats changes in electrograms of the visual cortex of alert animals were studied under photic stimulation in conditions of pharmacological action on monoamine (MA) brain systems. After injection of MA precursors (5-oxitriptophane and d, 1-dioxiphenylalanine) following phenomena were observed: a) decrease of the amplitude of the averaged evoked potentials to rhythmic photic stimuli (1-20 imp. sec.-1); b) an enhancement of fast (15-25 Hz) oscillations in the cortical spontaneous electrical activity and weakening and modification of the effects of the blockader of synthesis of MA-alpha-methyl-dioxiphenylalanine. Under light stimulation potentiation of MA precursors effects was observed in the frequency spectra of electrocorticograms. In the same conditions the specificity of action of cathecholamines precursor was revealed in the form of an increase of power of rhythms of 5-7 Hz and it; decrease in 2-3 Hz. Possible mechanisms of the revealed phenomena are discussed.

  8. Incomplete brain infarction of reperfused cortex may be quantitated with iomazenil

    DEFF Research Database (Denmark)

    Nakagawara, J; Sperling, B; Lassen, N A

    1997-01-01

    with ischemic stroke to detect viable neurons in cortex that appeared structurally intact on conventional neuroimaging studies. METHODS: Fourteen patients were selected by (1) angiography within 24 hours of onset showing embolic occlusion of an intracranial artery, (2) cerebral blood flow showing ischemia...... of moderate severity in 12 cases and spontaneous reflow in 2 cases, and (3) thrombolysis with reperfusion within 24 hours in most cases. Thirty reperfused cortical areas that remained structurally intact, 7 infarcted cortical areas, and 6 contralateral cerebellar areas with reduced blood flow were selected...

  9. Effect of propofol pretreatment on apoptosis in rat brain cortex after focal cerebral ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Haiyan Xu; Chengwei Zhang; Chunxiao Zhang

    2011-01-01

    The present study aimed to observe cortical expression of Bcl-2 and Bax, cysteine-dependent aspartate directed proteases-3 activity and apoptotic cell death in a rat model of middle cerebral artery occlusion pretreated with propofol. Results showed that, propofol pretreatment significantly reduced oxidative stress levels and attenuated neuronal apoptosis in the cortex of rats. Propofol pretreatment upregulated Bcl-2 expression, and downregulated Bax expression and cysteine-dependent aspartate directed proteases-3 activity. These findings indicate that propofol pretreatment inhibits cell apoptosis during focal cerebral ischemia/reperfusion injury. This neuroprotective effect is most likely achieved through the Bcl-2/Bax/cysteine-dependent aspartate directed proteases-3 pathway.

  10. Involvement of presynaptic H3 receptors in the inhibitory effect of histamine on serotonin release in the rat brain cortex.

    Science.gov (United States)

    Fink, K; Schlicker, E; Neise, A; Göthert, M

    1990-11-01

    Rat brain cortex slices or synaptosomes preincubated with 3H-serotonin were superfused with physiological salt solution (which, in the case of slices, contained citalopram, an inhibitor of serotonin uptake), and the effects of histamine and related drugs on the evoked tritium overflow were studied. The electrically (3 Hz) evoked tritium overflow from slices was inhibited by histamine and the H3 receptor agonists R-(-)-alpha-methylhistamine and N alpha-methylhistamine (pIC12.5 values: 6.41, 7.28 and 6.12, respectively), but not affected by the H1 receptor agonist 2-(2-thiazolyl)ethylamine and the H2 receptor agonist dimaprit (each at 10 mumol/l). The concentration-response curve for histamine was shifted to the right by the H3 receptor antagonists impromidine, burimamide and thioperamide (apparent pA2 values: 7.45, 5.97 and 7.88, respectively); the concentration-response curve of serotonin for its inhibitory effect on the electrically evoked overflow was not affected by the three drugs (apparent pA2 values: less than 5.5, less than 5.5 and less than 6.5). Given alone, impromidine, thioperamide and a low concentration of burimamide facilitated the electrically evoked overflow. In slices superfused with K(+)-rich, Ca2(+)-free solution containing tetrodotoxin throughout and in synaptosomes superfused with Ca2(+)-free solution, histamine inhibited the overflow evoked by introduction of Ca2+ (in synaptosomes, simultaneously with an increased amount of K+). In either tissue, the effect of histamine was counteracted by thioperamide. The results provide evidence that exogenous and probably also endogenous histamine inhibits serotonin release in the rat brain cortex via presynaptic histamine H3 receptors.

  11. Effects of cadmium on Bcl-2/ Bax expression ratio in rat cortex brain and hippocampus.

    Science.gov (United States)

    Mahdavi, S; Khodarahmi, P; Roodbari, N H

    2017-01-01

    To investigate the underlying mechanism of neurotoxicity of cadmium, we examined the effects of intraperitoneal injection of cadmium on messenger RNA (mRNA) expression of Bcl-2 (B-cell lymphoma 2) and Bax (Bcl2-associated x) genes and caspase-3/7 activation in rat hippocampus and frontal cortex. Twenty-eight male Wistar rats weighing 200-250 g were randomly divided into four groups. Control group received saline and three other groups received cadmium at doses of 1, 2 and 4 mg/kg (body weight) for 15 successive days. One day after the last injection, the hippocampus and frontal cortex were dissected and removed and then the expression of Bcl-2 and Bax genes was evaluated using real-time polymerase chain reaction and apoptotic studies was done using caspase-3/7 activation assay. Cadmium reduced the mRNA level of Bcl-2 in the control group at doses of 1 ( p Bax increased significantly compared to the control group at the doses of 1 ( p Bax was increased significantly compared to the control group at the doses of 2 and 4 mg/kg ( p Bax mRNA ratio induces cell apoptosis. Apoptotic effect of cadmium may be through the mitochondrial pathway by the activation of caspase-3/7.

  12. Dextromethorphan provides neuroprotection via anti-inflammatory and anti-excitotoxicity effects in the cortex following traumatic brain injury.

    Science.gov (United States)

    Pu, Benfang; Xue, Yonghua; Wang, Qingming; Hua, Chunhui; Li, Xinyuan

    2015-09-01

    Traumatic brain injury (TBI) is caused by primary and secondary injury mechanisms. TBI induces a certain amount of inflammatory responses and glutamate excitotoxicity that are believed to participate in the pathogenesis of secondary injury. The non‑narcotic anti‑tussive drug dextromethorphan (DM) has been reported to have a high safety profile in humans and its neuroprotective against a variety of disorders, including cerebral ischemia, epilepsy and acute brain injury. However, few studies have explored the underlying mechanisms of the neuroprotective effects of DM in animals in the setting of TBI. The aim of the present study was to investigate the neuroprotective effects of DM on TBI and to determine the underlying mechanisms. Rats were subjected to a controlled cortical impact (CCI) injury and randomly divided into three groups: Sham‑operated, TBI and DM treatment groups. The DM treatment group was administered DM (30 mg/kg of body weight, intraperitoneally) immediately after injury. It was identified that DM treatment following TBI significantly reduced brain edema and neurological deficits, as well as increased neuronal survival. These effects correlated with a decrease of tumor necrosis factor α, interleukin‑1β (IL‑1β) and IL‑6 protein expression and an increase of glutamate/aspartate transporter and glutamate transporter‑1 in the cortex of the brain. These results provided in vivo evidence that DM exerts neuroprotective effects via reducing inflammation and excitotoxicity induced following TBI. The present study has shed light on the potential use of DM as a neuroprotective agent in the treatment of cerebral injuries.

  13. Neuropeptides in atopic dermatitis

    Directory of Open Access Journals (Sweden)

    M. Cholis

    2001-09-01

    Full Text Available The nervous system, the immune system, and the cutaneous system are not independent systems, but are closely associated and use the same language of cytokines and neurotransmitters. Atopic dermatitis (AD is exacerbated by several factors, such as emotional stress, scratching and sweating. This review presents the role of neuropeptides (NP in AD. In AD, abnormalities occur in distribution of some types of neural filaments and in the associated active NP. Nerve fibre increases. Nerve fibres for substance-P (SP and calcitonin gene-related peptide (CGRP are positive, The cutaneous concentration of SP decreases while vasoactive-intestinal polypeptide (VIP increases. Immunohistochemical examination has revealed neuropeptide-Y (NPY-positive dendritic epidermal cells in AD lesions but no somatostatin (SOM fibres. Neuromediators modulate functions of all cutaneous cellular types, which are all part of the neuroimmunocutaneous system (NCIS: endothelial cells, glandular cells, fibroblasts, epidermal cells and immune cells. Conclusion: during the course of AD, the NICS is destabilized. Evidence show that NP can also be responsible for the induction and maintenance of the cutaneous inflammation process and confirm an involvement in the pathogenesis of AD. Release of the NP by cutaneous nerve potentially explains the role of emotional stress, scratching and sweating in exacerbation of AD. (Med J Indones 2001; 10: 197-200Keywords : neuroimmunocutaneous system, neurotransmitter, neurogenic inflammation

  14. Methamphetamine-induced changes in the mice hippocampal neuropeptide Y system: implications for memory impairment

    DEFF Research Database (Denmark)

    Gonçalves, J; Baptista, S; Olesen, MV

    2012-01-01

    Methamphetamine (METH) is a psychostimulant drug that causes irreversible brain damage leading to several neurological and psychiatric abnormalities, including cognitive deficits. Neuropeptide Y (NPY) is abundant in the mammalian central nervous system (CNS) and has several important functions...

  15. Up-regulation of GBP2 is Associated with Neuronal Apoptosis in Rat Brain Cortex Following Traumatic Brain Injury.

    Science.gov (United States)

    Miao, Qi; Ge, Meihong; Huang, Lili

    2017-02-27

    Guanylate binding protein 2 (GBP2) is one member of GBP family. Recently, GBP2 has been proposed to be a novel target of anti-cancer drugs. However, the role of GBP2 in the traumatic brain injury (TBI) is very limited. In this study, we sought to define GBP2's role in brain injury. GBP2 protein levels were significantly increased in the brain 3 days after injury, suggesting a functional role for GBP2 in TBI. Neuronal cells overexpressing GBP2 exhibited up-regulation of co-location of GBP2 and NeuN following TBI, suggesting that GBP2 potentiates the neuron apoptosis. To confirm the role of GBP2 in neuron apoptosis process, we employed a highly potent inhibitor of GBP2 (GBP2 RNAi). In H2O2-stimulated PC12 cells, in vitro blockade of GBP2 activity using GBP2 RNAi markedly attenuated the neuron apoptosis number. GBP2 RNAi also inhibited the expression levels of active caspase3 and p-Stat1. Furthermore, we found the expression of p-Stat1 in line with GBP2 and GBP2 interacted with p-Stat1 following TBI. The Jak2 inhibitor, AG490 inhibited this interaction and decreased the active caspase3 expression as well as promoted the functional recovery. Taken together, these data suggest that GBP2 RNAi has a protective effect in a rat TBI. This study demonstrates that GBP2 is an important positive regulator of TBI and is a promising therapeutic target for brain injury.

  16. Neuropeptide Y in the adult and fetal human pineal gland

    DEFF Research Database (Denmark)

    Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we s...

  17. Neuropeptides in Alzheimer's Disease : From Pathophysiological Mechanisms to Therapeutic Opportunities

    NARCIS (Netherlands)

    Van Dam, Debby; Van Dijck, Annemie; Janssen, Leen; De Deyn, Peter Paul

    2013-01-01

    Neuropeptides are found throughout the entire nervous system where they can act as neurotransmitter, neuromodulator or neurohormone. In those functions, they play important roles in the regulation of cognition and behavior. In brain disorders like Alzheimer's disease (AD), where abnormal cognition a

  18. Neuropeptide Y: An Anti-Aging Player?

    Science.gov (United States)

    Botelho, Mariana; Cavadas, Cláudia

    2015-11-01

    Accumulating evidence suggests that neuropeptide Y (NPY) has a role in aging and lifespan determination. In this review, we critically discuss age-related changes in NPY levels in the brain, together with recent findings concerning the contribution of NPY to, and impact on, six hallmarks of aging, specifically: loss of proteostasis, stem cell exhaustion, altered intercellular communication, deregulated nutrient sensing, cellular senescence, and mitochondrial dysfunction. Understanding how NPY contributes to, and counteracts, these hallmarks of aging will open new avenues of research on limiting damage related to aging.

  19. The predicting brain: anticipation of moving objects in human visual cortex

    NARCIS (Netherlands)

    Schellekens, W.

    2015-01-01

    The human brain is nearly constantly subjected to visual motion signals originating from a large variety of external sources. It is the job of the central nervous system to determine correspondence among visual motion input across spatially distant locations within certain time frames. In order to c

  20. Age-related differences in functional nodes of the brain cortex - a high model order group ICA study

    Directory of Open Access Journals (Sweden)

    Harri Littow

    2010-08-01

    Full Text Available Functional MRI measured with blood oxygen dependent (BOLD contrast in the absence of intermittent tasks reflects spontaneous activity of so called resting state networks (RSN of the brain. Group level independent component analysis (ICA of BOLD data can separate the human brain cortex into 42 independent RSNs. In this study we evaluated age related effects from primary motor and sensory, and, higher level control RSNs. 168 healthy subjects were scanned and divided into three groups: 55 adolescents (ADO, 13.2 ± 2.4 yrs, 59 young adults (YA, 22.2 ± 0.6yrs , and 54 older adults (OA, 42.7 ± 0.5 yrs, all with normal IQ. High model order group probabilistic ICA components (70 were calculated and dual regression analysis was used to compare 21 RSN’s spatial differences between groups. The power spectra were derived from individual ICA mixing matrix time series of the group analyses for frequency domain analysis. We show that primary sensory and motor networks tend to alter more in younger age groups, whereas associative and higher level cognitive networks consolidate and re-arrange until older adulthood. The change has a common trend: both spatial extent and the low frequency power of the RSN’s reduce with increasing age. We interpret these result as a sign of normal pruning via focusing of activity to less distributed local hubs.

  1. A brain-computer interface based on self-regulation of gamma-oscillations in the superior parietal cortex

    Science.gov (United States)

    Grosse-Wentrup, Moritz; Schölkopf, Bernhard

    2014-10-01

    Objective. Brain-computer interface (BCI) systems are often based on motor- and/or sensory processes that are known to be impaired in late stages of amyotrophic lateral sclerosis (ALS). We propose a novel BCI designed for patients in late stages of ALS that only requires high-level cognitive processes to transmit information from the user to the BCI. Approach. We trained subjects via EEG-based neurofeedback to self-regulate the amplitude of gamma-oscillations in the superior parietal cortex (SPC). We argue that parietal gamma-oscillations are likely to be associated with high-level attentional processes, thereby providing a communication channel that does not rely on the integrity of sensory- and/or motor-pathways impaired in late stages of ALS. Main results. Healthy subjects quickly learned to self-regulate gamma-power in the SPC by alternating between states of focused attention and relaxed wakefulness, resulting in an average decoding accuracy of 70.2%. One locked-in ALS patient (ALS-FRS-R score of zero) achieved an average decoding accuracy significantly above chance-level though insufficient for communication (55.8%). Significance. Self-regulation of gamma-power in the SPC is a feasible paradigm for brain-computer interfacing and may be preserved in late stages of ALS. This provides a novel approach to testing whether completely locked-in ALS patients retain the capacity for goal-directed thinking.

  2. Does noninvasive brain stimulation applied over the dorsolateral prefrontal cortex nonspecifically influence mood and emotional processing in healthy individuals?

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    Marine eMondino

    2015-10-01

    Full Text Available The dorsolateral prefrontal cortex (DLPFC is often targeted with noninvasive brain stimulation (NIBS to modulate in vivo human behaviors. This brain region plays a key role in mood, emotional processing and attentional processing of emotional information. In this article, we ask the question: when we target the DLPFC with NIBS, do we modulate these processes altogether, nonspecifically, or can we modulate them selectively? We thus review articles investigating the effects of NIBS applied over the DLPFC on mood, emotional processing and attentional processing of emotional stimuli in healthy subjects. We discuss that NIBS over the DLPFC can modulate emotional processing and attentional processing of emotional stimuli, without specifically influencing mood. Indeed, there seems to be a lack of evidence that NIBS over the DLPFC influence on mood in healthy individuals. Finally, there appears to be a hemispheric lateralization: when applied over the left DLPFC, NIBS improved processing of positive stimuli and reduced selective attention for stimuli expressing anger, whereas when applied over the right DLPFC, it increased selective attention for stimuli expressing anger.

  3. Issues in Localization of brain function: The case of lateralized frontal cortex in cognition, emotion, and psychopathology

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    Gregory A. Miller

    2013-01-01

    Full Text Available The appeal of simple, sweeping portraits of large-scale brain mechanisms relevant to psychological phenomena competes with a rich, complex research base. As a prominent example, two views of frontal brain organization have emphasized dichotomous lateralization as a function of either emotional valence (positive/negative or approach/avoidance motivation. Compelling findings support each. The literature has struggled to choose between them for three decades, without success. Both views are proving untenable as comprehensive models. Recent evidence indicates that positive valence and approach motivation are associated with different areas in the left hemisphere. Evidence of other frontal lateralizations, involving distinctions among dimensions of depression and anxiety, make a dichotomous view even more problematic. Hemodynamic and electromagnetic neuroimaging studies suggest considerable functional differentiation, in specialization and activation, of subregions of frontal cortex, including their connectivity to each other and to other regions. Such findings contribute to a more nuanced understanding of functional localization that accommodates aspects of multiple theoretical perspectives.

  4. Cognitive signals for brain-machine interfaces in posterior parietal cortex include continuous 3D trajectory commands.

    Science.gov (United States)

    Hauschild, Markus; Mulliken, Grant H; Fineman, Igor; Loeb, Gerald E; Andersen, Richard A

    2012-10-16

    Cortical neural prosthetics extract command signals from the brain with the goal to restore function in paralyzed or amputated patients. Continuous control signals can be extracted from the motor cortical areas, whereas neural activity from posterior parietal cortex (PPC) can be used to decode cognitive variables related to the goals of movement. Because typical activities of daily living comprise both continuous control tasks such as reaching, and tasks benefiting from discrete control such as typing on a keyboard, availability of both signals simultaneously would promise significant increases in performance and versatility. Here, we show that PPC can provide 3D hand trajectory information under natural conditions that would be encountered for prosthetic applications, thus allowing simultaneous extraction of continuous and discrete signals without requiring multisite surgical implants. We found that limb movements can be decoded robustly and with high accuracy from a small population of neural units under free gaze in a complex 3D point-to-point reaching task. Both animals' brain-control performance improved rapidly with practice, resulting in faster target acquisition and increasing accuracy. These findings disprove the notion that the motor cortical areas are the only candidate areas for continuous prosthetic command signals and, rather, suggests that PPC can provide equally useful trajectory signals in addition to discrete, cognitive variables. Hybrid use of continuous and discrete signals from PPC may enable a new generation of neural prostheses providing superior performance and additional flexibility in addressing individual patient needs.

  5. Diagnostic benefits of presurgical fMRI in patients with brain tumours in the primary sensorimotor cortex

    Energy Technology Data Exchange (ETDEWEB)

    Wengenroth, Martina; Blatow, M.; Guenther, J. [University of Heidelberg Medical School, Department of Neuroradiology, Heidelberg (Germany); Akbar, M. [University of Heidelberg Medical School, Department of Orthopaedics, Heidelberg (Germany); Tronnier, V.M. [University of Schleswig-Holstein, Department of Neurosurgery, Luebeck (Germany); Stippich, C. [University Hospital Basle, Department of Diagnostic and Interventional Neuroradiology, Basle (Switzerland)

    2011-07-15

    Reliable imaging of eloquent tumour-adjacent brain areas is necessary for planning function-preserving neurosurgery. This study evaluates the potential diagnostic benefits of presurgical functional magnetic resonance imaging (fMRI) in comparison to a detailed analysis of morphological MRI data. Standardised preoperative functional and structural neuroimaging was performed on 77 patients with rolandic mass lesions at 1.5 Tesla. The central region of both hemispheres was allocated using six morphological and three functional landmarks. fMRI enabled localisation of the motor hand area in 76/77 patients, which was significantly superior to analysis of structural MRI (confident localisation of motor hand area in 66/77 patients; p < 0.002). FMRI provided additional diagnostic information in 96% (tongue representation) and 97% (foot representation) of patients. FMRI-based presurgical risk assessment correlated in 88% with a positive postoperative clinical outcome. Routine presurgical FMRI allows for superior assessment of the spatial relationship between brain tumour and motor cortex compared with a very detailed analysis of structural 3D MRI, thus significantly facilitating the preoperative risk-benefit assessment and function-preserving surgery. The additional imaging time seems justified. FMRI has the potential to reduce postoperative morbidity and therefore hospitalisation time. (orig.)

  6. RIC-7 promotes neuropeptide secretion.

    Directory of Open Access Journals (Sweden)

    Yingsong Hao

    2012-01-01

    Full Text Available Secretion of neurotransmitters and neuropeptides is mediated by exocytosis of distinct secretory organelles, synaptic vesicles (SVs and dense core vesicles (DCVs respectively. Relatively little is known about factors that differentially regulate SV and DCV secretion. Here we identify a novel protein RIC-7 that is required for neuropeptide secretion in Caenorhabditis elegans. The RIC-7 protein is expressed in all neurons and is localized to presynaptic terminals. Imaging, electrophysiology, and behavioral analysis of ric-7 mutants indicates that acetylcholine release occurs normally, while neuropeptide release is significantly decreased. These results suggest that RIC-7 promotes DCV-mediated secretion.

  7. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    Energy Technology Data Exchange (ETDEWEB)

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona [Sanjay Gandhi Post Graduate Institute of Medical Sciences, Department of Radiodiagnosis, Lucknow, UP (India); Husain, Nuzhat; Srivastava, Savita [CSM Medical University, Department of Pathology, Lucknow (India); Rathore, Ram K.S.; Sarma, Manoj K. [Indian Institute of Technology, Department of Mathematics and Statistics, Kanpur (India); Malik, Gyanendra K. [CSM Medical University, Department of Pediatrics, Lucknow (India); Das, Vinita [CSM Medical University, Department of Obstetrics and Gynecology, Lucknow (India); Pradhan, Mandakini [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Medical Genetics, Lucknow (India); Pandey, Chandra M. [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Biostatistics, Lucknow (India); Narayana, Ponnada A. [University of Texas Medical School at Houston, Department of Diagnostic and Interventional Imaging, Houston, TX (United States)

    2009-09-15

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA {<=} 28 weeks for frontal cortical region and GA{<=}22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  8. Arrhenius plots of membrane-bound enzymes of mitochondria and microsomes in the brain cortex of developing and old rats.

    Science.gov (United States)

    Gorgani, M N; Pour-Rahimi, F; Meisami, E

    1986-06-01

    old and mature brain cortex. It is concluded that the enzymes of inner and outer mitochondrial membranes as well as the oxidative enzymes of microsomal membranes may show differential patterns of change in lipid-protein-interaction during development and aging, the changes being more marked in development than in aging.

  9. Calretinin and parvalbumin immunoreactive interneurons in the retrosplenial cortex of the rat brain: Qualitative and quantitative analyses.

    Science.gov (United States)

    Salaj, Martin; Druga, Rastislav; Cerman, Jiří; Kubová, Hana; Barinka, Filip

    2015-11-19

    The retrosplenial cortex (RSC) is a mesocortical region broadly involved with memory and navigation. It shares many characteristics with the perirhinal cortex (PRC), both of which appear to be significantly involved in the spreading of epileptic activity. We hypothesized that RSC possesses an interneuronal composition similar to that of PRC. To prove the hypothesis we studied the general pattern of calretinin (CR) and parvalbumin (PV) immunoreactivity in the RSC of the rat brain, its optical density as well as the morphological features and density of CR- and PV-immunoreactive (CR+ and PV+) interneurons. We also analyzed the overall neuronal density on Nissl-stained sections in RSC. Finally, we compared our results with our earlier analysis of PRC (Barinka et al., 2012). Compared to PRC, RSC was observed to have a higher intensity of PV staining and lower intensity of CR staining of neuropil. Vertically-oriented bipolar neurons were the most common morphological type among CR+ neurons. The staining pattern did not allow for a similarly detailed analysis of somatodendritic morphology of PV+ neurons. RSC possessed lower absolute (i.e., neurons/mm(3)) and relative (i.e., percentage of the overall neuronal population) densities of CR+ neurons and similar absolute and lower relative densities of PV+ neurons relative to PRC. CR: PV neuronal ratio in RSC (1:2 in area 29 and 1:2.2 in area 30) differed from PRC (1:1.2 in area 35 and 1:1.7 in area 36). In conclusion, RSC, although similar in many aspects to PRC, differs strikingly in the interneuronal composition relative to PRC.

  10. Ageing alters the supramolecular architecture of OxPhos complexes in rat brain cortex.

    Science.gov (United States)

    Frenzel, Monika; Rommelspacher, Hans; Sugawa, Michiru D; Dencher, Norbert A

    2010-08-01

    Activity and stability of life-supporting proteins are determined not only by their abundance and by post-translational modifications, but also by specific protein-protein interactions. This holds true both for signal-transduction and energy-converting cascades. For vital processes such as life-span control and senescence, to date predominantly age-dependent alterations in abundance and to lesser extent in post-translational modifications of proteins are examined to elucidate the cause of ageing at the molecular level. In mitochondria of rat cortex, we quantified profound changes in the proportion of supramolecular assemblies (supercomplexes) of the respiratory chain complexes I, III(2), IV as well as of the MF(o)F(1) ATP synthase (complex V) by 2D-native/SDS electrophoresis and fluorescent staining. Complex I was present solely in supercomplexes and those lacking complex IV were least stable in aged animals (2.4-fold decline). The ATP synthase was confirmed as a prominent target of age-associated degradation by an overall decline in abundance of 1.5-fold for the monomer and an 2.8-fold increase of unbound F(1). Oligomerisation of the ATP synthase increases during ageing and might modulate the cristae architecture. These data could explain the link between ageing and respiratory control as well as ROS generation.

  11. Benefits of physical exercise on the aging brain: the role of the prefrontal cortex.

    Science.gov (United States)

    Berchicci, Marika; Lucci, Giuliana; Di Russo, Francesco

    2013-11-01

    Motor planning in older adults likely relies on the overengagement of the prefrontal cortex (PFC) and is associated with slowness of movement and responses. Does a physically active lifestyle counteract the overrecruitment of the PFC during action preparation? This study used high-resolution electroencephalography to measure the effect of physical exercise on the executive functions of the PFC preceding a visuomotor discriminative task. A total of 130 participants aged 15-86 were divided into two groups based on physical exercise participation. The response times and accuracy and the premotor activity of the PFC were separately correlated with age for the two groups. The data were first fit with a linear function and then a higher order polynomial function. We observed that after 35-40 years of age, physically active individuals have faster response times than their less active peers and showed no signs of PFC hyperactivity during motor planning. The present findings show that physical exercise could speed up the response of older people and reveal that also in middle-aged people, moderate-to-high levels of physical exercise benefits the planning/execution of a response and the executive functions mediated by the PFC, counteracting the neural overactivity often observed in the elderly adults.

  12. Brain cells in the avian 'prefrontal cortex' code for features of slot-machine-like gambling.

    Directory of Open Access Journals (Sweden)

    Damian Scarf

    Full Text Available Slot machines are the most common and addictive form of gambling. In the current study, we recorded from single neurons in the 'prefrontal cortex' of pigeons while they played a slot-machine-like task. We identified four categories of neurons that coded for different aspects of our slot-machine-like task. Reward-Proximity neurons showed a linear increase in activity as the opportunity for a reward drew near. I-Won neurons fired only when the fourth stimulus of a winning (four-of-a-kind combination was displayed. I-Lost neurons changed their firing rate at the presentation of the first nonidentical stimulus, that is, when it was apparent that no reward was forthcoming. Finally, Near-Miss neurons also changed their activity the moment it was recognized that a reward was no longer available, but more importantly, the activity level was related to whether the trial contained one, two, or three identical stimuli prior to the display of the nonidentical stimulus. These findings not only add to recent neurophysiological research employing simulated gambling paradigms, but also add to research addressing the functional correspondence between the avian NCL and primate PFC.

  13. Dietary fat induces sustained reward response in the human brain without primary taste cortex discrimination

    Directory of Open Access Journals (Sweden)

    Hélène eTzieropoulos

    2013-02-01

    Full Text Available To disentangle taste from reward responses in the human gustatory cortex, we combined high density electro-encephalography with a gustometer delivering tastant puffs to the tip of the tongue. Stimuli were pure tastants (salt solutions at two concentrations, caloric emulsions of identical taste (two milk preparations differing in fat content and a mixture of high fat milk with the lowest salt concentration. Early event-related potentials showed a dose-response effect for increased taste intensity, with higher amplitude and shorter latency for high compared to low salt concentration, but not for increased fat content. However, the amplitude and distribution of late potentials were modulated by fat content independently of reported intensity and discrimination. Neural source estimation revealed a sustained activation of reward areas to the two high-fat stimuli. The results suggest calorie detection through specific sensors on the tongue independent of perceived taste. Finally, amplitude variation of the first peak in the event-related potential to the different stimuli correlated with papilla density, suggesting a higher discrimination power for subjects with more fungiform papillae.

  14. Differential cellular expression of organic anion transporting peptides OATP1A2 and OATP2B1 in the human retina and brain: implications for carrier-mediated transport of neuropeptides and neurosteriods in the CNS.

    Science.gov (United States)

    Gao, Bo; Vavricka, Stephan R; Meier, Peter J; Stieger, Bruno

    2015-07-01

    Organic anion transporting polypeptides (OATPs) are polyspecific organic anion transporters, which are expressed in the blood-brain barrier, the choroid plexus, and other organs. The physiologic function of OATPs in extrahepatic tissues remains ambiguous. In rat retina, members of the OATP family are expressed. We therefore investigated the human retina for the expression of OATP1A2 and OATP2B1 and extended the study to human brain. Furthermore, we searched for peptide neurotransmitters as novel OATP substrates. OATP1A2 displayed a broad expression pattern in human retina as assessed by immunofluorescence localization. It is expressed in photoreceptor bodies and somas of amacrine cells. OATP1B2 expression is restricted to the inner nuclear layer and to the inner plexiform layer. Using paraffin sections from human cortex, cerebellum, and hippocampus, OATP1A2 was localized to neurons and neuronal processes, while OATP2B1 is expressed in endothelial cells of brain capillaries. Substance P and vasoactive intestinal peptide were identified as substrates for OATP1A2 and OATP2B1. Double-labeling immunofluorescence of human retina demonstrated the presence of substance P and of vasoactive intestinal peptides in neurons expressing OATP1A2 and OATP2B1, respectively. The expression of OATP1A2 and OATP2B1 in retinal neurons implies a role of these transporters in the reuptake of peptide neurotransmitters released from retinal neurons. The abundant expression of OATP1A2 in brain neurons points to the possibility that OATP1A2 could be involved in the homeostasis of neurosteroids. The high expression of OATP2B1 in brain capillaries supports an important function of OATPs in substance penetration across the blood-brain barrier.

  15. Age-related changes of brain iron load changes in the frontal cortex in APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Xian-hui, Dong; Wei-juan, Gao; Tie-mei, Shao; Hong-lin, Xie; Jiang-tao, Bai; Jing-yi, Zhao; Xi-qing, Chai

    2015-04-01

    Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, associated with major social and economic costs to society. Iron can catalyze damaging free radical reactions. With age, iron accumulates in brain frontal cortex regions and may contribute to the risk of AD. In this communication, we investigated the age-related brain iron load changes in the frontal cortex of 6- and 12-month-old C57BL/6J (C57) and APPswe/PS1ΔE9 (APP/PS1) double transgenic mouse by using graphite furnace atomic absorption spectrometry (GFAAS) and Perls' reaction. In the present study, we also evaluated the age-related changes of DMT1 and FPN1 by using Western blot and qPCR. We found that compared with 6-month-old APP/PS1 mice and the 12-month-old C57 mice, the 12-month-old APP/PS1 mice had increased iron load in the frontal cortex. The levels of DMT1 were significantly increased and the FPN1 were significantly reduced in the frontal cortex of the 12-month-old APP/PS1 mice than that in the 6-month-old APP/PS1 mice and 12-month-old C57 mice. We conclude that in AD damage occurs in conjunction with iron accumulation, and the brain iron load associated with loss control of the brain iron metabolism related protein DMT1 and FPN1 expressions.

  16. Mirror-image discrimination in the literate brain: a causal role for the left occpitotemporal cortex.

    Science.gov (United States)

    Nakamura, Kimihiro; Makuuchi, Michiru; Nakajima, Yasoichi

    2014-01-01

    Previous studies show that the primate and human visual system automatically generates a common and invariant representation from a visual object image and its mirror reflection. For humans, however, this mirror-image generalization seems to be partially suppressed through literacy acquisition, since literate adults have greater difficulty in recognizing mirror images of letters than those of other visual objects. At the neural level, such category-specific effect on mirror-image processing has been associated with the left occpitotemporal cortex (L-OTC), but it remains unclear whether the apparent "inhibition" on mirror letters is mediated by suppressing mirror-image representations covertly generated from normal letter stimuli. Using transcranial magnetic stimulation (TMS), we examined how transient disruption of the L-OTC affects mirror-image recognition during a same-different judgment task, while varying the semantic category (letters and non-letter objects), identity (same or different), and orientation (same or mirror-reversed) of the first and second stimuli. We found that magnetic stimulation of the L-OTC produced a significant delay in mirror-image recognition for letter-strings but not for other objects. By contrast, this category specific impact was not observed when TMS was applied to other control sites, including the right homologous area and vertex. These results thus demonstrate a causal link between the L-OTC and mirror-image discrimination in literate people. We further suggest that left-right sensitivity for letters is not achieved by a local inhibitory mechanism in the L-OTC but probably relies on the inter-regional coupling with other orientation-sensitive occipito-parietal regions.

  17. Mirror-image discrimination in the literate brain: A causal role for the left occpitotemporal cortex

    Directory of Open Access Journals (Sweden)

    Kimihiro eNakamura

    2014-05-01

    Full Text Available Previous studies show that the primate and human visual system automatically generates a common and invariant representation from a visual object image and its mirror reflection. For humans, however, this mirror-image generalization seems to be partially suppressed through literacy acquisition, since literate adults have greater difficulty in recognizing mirror images of letters than those of other visual objects. At the neural level, such category-specific effect on mirror-image processing has been associated with the left occpitotemporal cortex (L-OTC, but it remains unclear whether the apparent inhibition on mirror letters is mediated by suppressing mirror-image representations covertly generated from normal letter stimuli. Using transcranial magnetic stimulation (TMS, we examined how transient disruption of the L-OTC affects mirror-image recognition during a same-different judgment task, while varying the semantic category (letters and non-letter objects, identity (same or different and orientation (same or mirror-reversed of the first and second stimuli. We found that magnetic stimulation of the L-OTC produced a significant delay in mirror-image recognition for letter-strings but not for other objects. By contrast, this category specific impact was not observed when TMS was applied to other control sites, including the right homologous area and vertex. These results thus demonstrate a causal link between the L-OTC and mirror-image discrimination in literate people. We further suggest that left-right sensitivity for letters is not achieved by a local inhibitory mechanism in the L-OTC but probably relies on the inter-regional coupling with other orientation-sensitive occipito-parietal regions.

  18. Ethological principles predict the neuropeptides co-opted to influence parenting

    Science.gov (United States)

    Cunningham, Christopher B.; Badgett, Majors J.; Meagher, Richard B.; Orlando, Ron; Moore, Allen J.

    2017-01-01

    Ethologists predicted that parental care evolves by modifying behavioural precursors in the asocial ancestor. As a corollary, we predict that the evolved mechanistic changes reside in genetic pathways underlying these traits. Here we test our hypothesis in female burying beetles, Nicrophorus vespilloides, an insect where caring adults regurgitate food to begging, dependent offspring. We quantify neuropeptide abundance in brains collected from three behavioural states: solitary virgins, individuals actively parenting or post-parenting solitary adults and quantify 133 peptides belonging to 18 neuropeptides. Eight neuropeptides differ in abundance in one or more states, with increased abundance during parenting in seven. None of these eight neuropeptides have been associated with parental care previously, but all have roles in predicted behavioural precursors for parenting. Our study supports the hypothesis that predictable traits and pathways are targets of selection during the evolution of parenting and suggests additional candidate neuropeptides to study in the context of parenting. PMID:28145404

  19. A ‘complex’ of brain metabolites distinguish altered chemistry in the cingulate cortex of episodic migraine patients

    Directory of Open Access Journals (Sweden)

    L. Becerra

    2016-01-01

    Full Text Available Despite the prevalence of migraine, the pathophysiology of the disease remains unclear. Current understanding of migraine has alluded to the possibility of a hyperexcitable brain. The aim of the current study is to investigate human brain metabolite differences in the anterior cingulate cortex (ACC during the interictal phase in migraine patients. We hypothesized that there may be differences in levels of excitatory neurotransmitters and/or their derivatives in the migraine cohort in support of the theory of hyperexcitability in migraine. 2D J-resolved proton magnetic resonance spectroscopy (1H-MRS data were acquired on a 3 Tesla (3 T MRI from a voxel placed over the ACC of 32 migraine patients (MP; 23 females, 9 males, age 33 ± 9.6 years and 33 healthy controls (HC; 25 females, 8 males, age 32 ± 9.6 years. Amplitude correlation matrices were constructed for each subject to evaluate metabolite discriminability. ProFit-estimated metabolite peak areas were normalized to a water reference signal to assess subject differences. The initial analysis of variance (ANOVA was performed to test for group differences for all metabolites/creatine (Cre ratios between healthy controls and migraineurs but showed no statistically significant differences. In addition, we used a multivariate approach to distinguish migraineurs from healthy subjects based on the metabolite/Cre ratio. A quadratic discriminant analysis (QDA model was used to identify 3 metabolite ratios sufficient to minimize minimum classification error (MCE. The 3 selected metabolite ratios were aspartate (Asp/Cre, N-acetyl aspartate (NAA/Cre, and glutamine (Gln/Cre. These findings are in support of a ‘complex’ of metabolite alterations, which may underlie changes in neuronal chemistry in the migraine brain. Furthermore, the parallel changes in the three-metabolite ‘complex’ may confer more subtle but biological processes that are ongoing. The data also support the current theory

  20. Processing of visual gravitational motion in the peri-sylvian cortex: Evidence from brain-damaged patients.

    Science.gov (United States)

    Maffei, Vincenzo; Mazzarella, Elisabetta; Piras, Fabrizio; Spalletta, Gianfranco; Caltagirone, Carlo; Lacquaniti, Francesco; Daprati, Elena

    2016-05-01

    Rich behavioral evidence indicates that the brain estimates the visual direction and acceleration of gravity quite accurately, and the underlying mechanisms have begun to be unraveled. While the neuroanatomical substrates of gravity direction processing have been studied extensively in brain-damaged patients, to our knowledge no such study exists for the processing of visual gravitational motion. Here we asked 31 stroke patients to intercept a virtual ball moving along the vertical under either natural gravity or artificial reversed gravity. Twenty-seven of them also aligned a luminous bar to the vertical direction (subjective visual vertical, SVV). Using voxel-based lesion-symptom mapping as well as lesion subtraction analysis, we found that lesions mainly centered on the posterior insula are associated with greater deviations of SVV, consistent with several previous studies. Instead, lesions mainly centered on the parietal operculum decrease the ability to discriminate natural from unnatural gravitational acceleration with a timed motor response in the interception task. Both the posterior insula and the parietal operculum belong to the vestibular cortex, and presumably receive multisensory information about the gravity vector. We speculate that an internal model estimating the effects of gravity on visual objects is constructed by transforming the vestibular estimates of mechanical gravity, which are computed in the brainstem and cerebellum, into internalized estimates of virtual gravity, which are stored in the cortical vestibular network. The present lesion data suggest a specific role for the parietal operculum in detecting the mismatch between predictive signals from the internal model and the online visual signals.

  1. Depolarizing and calcium-mobilizing stimuli fail to enhance synthesis and release of endocannabinoids from rat brain cerebral cortex slices.

    Science.gov (United States)

    Sarmad, Sarir; Alexander, Stephen P H; Barrett, David A; Marsden, Charles A; Kendall, David A

    2011-05-01

    The concentrations of the endocannabinoids 2-arachidonoylglycerol (2-AG) and N-arachidonylethanolamine (anandamide) were examined in rat brain cerebral cortex slices and surrounding medium. Basal concentrations of endocannabinoids were similar to those identified previously in rat brain, with anandamide content being much lower (19 pmol/g) than that of 2-AG (7300 pmol/g). In contrast, basal concentrations in the surrounding medium were proportionally much lower for 2-arachidonoylglycerol (16 pmol/mL) compared to anandamide (0.6 pmol/mL). Incubation of slices with glutamate receptor agonists, depolarizing concentrations of KCl, or ionomycin failed to alter tissue concentrations of endocannabinoids, while endocannabinoids in the medium were unaltered by elevated KCl. Cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester, an inhibitor of fatty acid amide hydrolase, significantly enhanced tissue concentrations of anandamide (and related N-acylethanolamines), without altering 2-AG, while evoking proportional elevations of anandamide in the medium. Removal of extracellular calcium ions failed to alter tissue concentrations of anandamide, but significantly reduced 2-AG in the tissue by 90% and levels in the medium to below the detection limit. Supplementation of the medium with 50 μM N-oleoylethanolamine only raised tissue concentrations of N-oleoylethanolamine in the presence of cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester and failed to alter either tissue or medium anandamide or 2-AG concentrations. These results highlight the ongoing turnover of endocannabinoids, and the importance of calcium ions in maintaining 2-AG concentrations in this tissue.

  2. Alterations in BDNF and synapsin I within the occipital cortex and hippocampus after mild traumatic brain injury in the developing rat: reflections of injury-induced neuroplasticity.

    Science.gov (United States)

    Griesbach, Grace Sophia; Hovda, David Allen; Molteni, Raffaella; Gomez-Pinilla, Fernando

    2002-07-01

    Brain-derived neurotrophic factor (BDNF), its signal transduction receptor trkB, and its downstream effector, synapsin I, were measured in the hippocampus and occipital cortex of young animals after fluid-percussion brain injury (FPI). Isofluorane anaesthetized postnatal day 19 rats were subjected to a mild lateral FPI or sham injury. Rats were sacrificed at 24 h, 7 days, or 14 days after injury in order to determine mRNA expression. Additional animals were sacrificed at 7 and 14 days after injury for protein analysis. Only FPI animals exhibited hemispheric differences in BDNF levels. These animals exhibited a contralateral increase, ranging from 40% to 75%, in BDNF mRNA within both the hippocampus and occipital cortex at 24 h and 7 days after injury. The increase in message within the occipital cortex was accompanied by an increase in BDNF protein at 7 and 14 days after injury. However, hippocampal BDNF protein increased in both hemispheres at postinjury day 7 and was restricted to the ipsilateral hippocampus at postinjury day 14. At postinjury day 7, both trkB and synapsin I mRNA expression increased ipsilaterally and decreased contralaterally in the occipital cortex. In addition, synapsin I phosphorylation was increased by 20% in the ipsilateral cortex and by 30% in the hippocampus on this day. These results indicate that the developing brain responds to a mild injury by modifying factors related to synaptic plasticity and suggest that regions remote from the site of injury express neurotrophic signals potentially needed for compensatory responses.

  3. Neuropeptides and neuropeptide receptors: drug targets, and peptide and non-peptide ligands: a tribute to Prof. Dieter Seebach.

    Science.gov (United States)

    Hoyer, Daniel; Bartfai, Tamas

    2012-11-01

    The number of neuropeptides and their corresponding receptors has increased steadily over the last fourty years: initially, peptides were isolated from gut or brain (e.g., Substance P, somatostatin), then by targeted mining in specific regions (e.g., cortistatin, orexin in the brain), or by deorphanization of G-protein-coupled receptors (GPCRs; orexin, ghrelin receptors) and through the completion the Human Genome Project. Neuropeptides (and their receptors) have regionally restricted distributions in the central and peripheral nervous system. The neuropeptide signaling is somewhat more distinct spatially than signaling with classical, low-molecular-weight neurotransmitters that are more widely expressed, and, therefore, one assumes that drugs acting at neuropeptide receptors may have more selective pharmacological actions with possibly fewer side effects than drugs acting on glutamatergic, GABAergic, monoaminergic, or cholinergic systems. Neuropeptide receptors, which may have a few or multiple subtypes and splice variants, belong almost exclusively to the GPCR family also known as seven-transmembrane receptors (7TM), a favorite class of drug targets in the pharmaceutical industry. Most neuropeptides are co-stored and co-released with classic neurotransmitters, albeit often only at higher frequencies of stimulation or at bursting activity, thus restricting the neuropeptide signaling to specific circumstances, another reason to assume that neuropeptide drug mimics may have less side effects. Neuropeptides possess a wide spectrum of functions from neurohormone, neurotransmitter to growth factor, but also as key inflammatory mediators. Neuropeptides become 'active' when the nervous system is challenged, e.g., by stress, injury, drug abuse, or neuropsychiatric disorders with genetic, epigenetic, and/or environmental components. The unsuspected number of true neuropeptides and their cognate receptors provides opportunities to identify novel targets for the treatment of

  4. Correlation-based model of artificially induced plasticity in motor cortex by a bidirectional brain-computer interface.

    Directory of Open Access Journals (Sweden)

    Guillaume Lajoie

    2017-02-01

    Full Text Available Experiments show that spike-triggered stimulation performed with Bidirectional Brain-Computer-Interfaces (BBCI can artificially strengthen connections between separate neural sites in motor cortex (MC. When spikes from a neuron recorded at one MC site trigger stimuli at a second target site after a fixed delay, the connections between sites eventually strengthen. It was also found that effective spike-stimulus delays are consistent with experimentally derived spike-timing-dependent plasticity (STDP rules, suggesting that STDP is key to drive these changes. However, the impact of STDP at the level of circuits, and the mechanisms governing its modification with neural implants remain poorly understood. The present work describes a recurrent neural network model with probabilistic spiking mechanisms and plastic synapses capable of capturing both neural and synaptic activity statistics relevant to BBCI conditioning protocols. Our model successfully reproduces key experimental results, both established and new, and offers mechanistic insights into spike-triggered conditioning. Using analytical calculations and numerical simulations, we derive optimal operational regimes for BBCIs, and formulate predictions concerning the efficacy of spike-triggered conditioning in different regimes of cortical activity.

  5. Modulation of antioxidant enzyme expression by PTU-induced hypothyroidism in cerebral cortex of postnatal rat brain.

    Science.gov (United States)

    Bhanja, Shravani; Jena, Srikanta

    2013-01-01

    This study aimed to elucidate the effect of 6-n-propylthiouracil (PTU)-induced hypothyroidism on oxidative stress parameters and expression of antioxidant enzymes in cerebral cortex of rat brain during postnatal development. A significant decrease in levels of lipid peroxidation and H(2)O(2) were seen in 7 and 30 days old PTU-treated rats with respect to their controls. Significantly decreased activities of superoxide dismutase (SOD) and catalase (CAT) along with the translated products of SOD1 and SOD2 were observed in 7, 15 and 30 days old PTU-treated rats as compared to their respective controls. However, increase in translated product of CAT was seen in all age groups of PTU-treated rats. Glutathione peroxidase activity was decreased in 7 days and increased in 15 days old PTU-treated rats with respect to their control groups. Histological sections clearly show a decline in neuronal migration with neurons packed together in the hypothyroid group as compared to the control.

  6. Structural brain mutant of Drosophila melanogaster with reduced cell number in the medulla cortex and with normal optomotor yaw response

    Science.gov (United States)

    Fischbach, K. F.; Heisenberg, M.

    1981-01-01

    KS58, one out of six known alleles of the small optic lobes (sol) gene in Drosophila melanogaster, reduces the cell number in the medulla cortex by degeneration of ganglion cells in the pupae to about 50%. Also, about half the volume of the medulla and lobula complex neuropils is missing. Many Golgistained cells in the mutant optic lobes resemble their homologues in wild type. However, special classes of transmedullary columnar neurons projecting to the lobula or to both lobula and lobula plate are not seen in the mutant. Some neurons linking the lobula complex to the central brain send branches to the medulla (the branches do not exist in wild type); some other types seem to be missing. The fate mapping of the KS58 focus reveals a location ventral to the head bristles and in sine oculis (so) flies the mutation further reduces the rudiments of the optic lobes normally seen. Therefore the sol phenotype is not induced by mutant eyes and the primary gene action seems to be on nervous tissue. The structural alterations of the small optic lobes are reflected in visual orientation behavior. The optomotor yaw response, however, is almost quantitatively preserved. The respective neural network should still be present in the mutant optic lobes. Images PMID:16592962

  7. Tactile Object Familiarity in the Blind Brain Reveals the Supramodal Perceptual-Mnemonic Nature of the Perirhinal Cortex

    Science.gov (United States)

    Cacciamani, Laura; Likova, Lora T.

    2016-01-01

    This study is the first to investigate the neural underpinnings of tactile object familiarity in the blind during both perception and memory. In the sighted, the perirhinal cortex (PRC) has been implicated in the assessment of visual object familiarity—a crucial everyday task—as evidenced by reduced activation when an object becomes familiar. Here, to examine the PRC’s role in tactile object familiarity in the absence of vision, we trained blind participants on a unique memory-guided drawing technique and measured brain activity while they perceptually explored raised-line drawings, drew them from tactile memory, and scribbled (control). Functional magnetic resonance imaging (fMRI) before and after a week of training revealed a significant decrease in PRC activation from pre- to post-training (i.e., from unfamiliar to familiar) during perceptual exploration as well as memory-guided drawing, but not scribbling. This familiarity-based reduction is the first evidence that the PRC represents tactile object familiarity in the blind. Furthermore, the finding of this effect during both tactile perception and tactile memory provides the critical link in establishing the PRC as a structure whose representations are supramodal for both perception and memory. PMID:27148002

  8. Correlation-based model of artificially induced plasticity in motor cortex by a bidirectional brain-computer interface

    Science.gov (United States)

    Lajoie, Guillaume; Kalaska, John F.; Fairhall, Adrienne L.; Fetz, Eberhard E.

    2017-01-01

    Experiments show that spike-triggered stimulation performed with Bidirectional Brain-Computer-Interfaces (BBCI) can artificially strengthen connections between separate neural sites in motor cortex (MC). When spikes from a neuron recorded at one MC site trigger stimuli at a second target site after a fixed delay, the connections between sites eventually strengthen. It was also found that effective spike-stimulus delays are consistent with experimentally derived spike-timing-dependent plasticity (STDP) rules, suggesting that STDP is key to drive these changes. However, the impact of STDP at the level of circuits, and the mechanisms governing its modification with neural implants remain poorly understood. The present work describes a recurrent neural network model with probabilistic spiking mechanisms and plastic synapses capable of capturing both neural and synaptic activity statistics relevant to BBCI conditioning protocols. Our model successfully reproduces key experimental results, both established and new, and offers mechanistic insights into spike-triggered conditioning. Using analytical calculations and numerical simulations, we derive optimal operational regimes for BBCIs, and formulate predictions concerning the efficacy of spike-triggered conditioning in different regimes of cortical activity. PMID:28151957

  9. "Brain is to thought as stomach is to ??": investigating the role of rostrolateral prefrontal cortex in relational reasoning.

    Science.gov (United States)

    Wendelken, Carter; Nakhabenko, Denis; Donohue, Sarah E; Carter, Cameron S; Bunge, Silvia A

    2008-04-01

    Brain imaging studies suggest that the rostrolateral prefrontal cortex (RLPFC), is involved in relational reasoning. Functional magnetic resonance imaging (fMRI) studies involving Raven's Progressive Matrices or verbal propositional analogies indicate that the RLPFC is engaged by tasks that require integration across multiple relational structures. Several studies have shown that the RLPFC is more active when people must evaluate an analogy (e.g., Is shoe to foot as glove is to hand?) than when they must simply evaluate two individual semantic relationships, consistent with the hypothesis that this region is important for relational integration. The current fMRI investigation further explores the role of the RLPFC in reasoning and relational integration by comparing RLPFC activation across four different propositional analogy conditions. Each of the four conditions required either relation completion (e.g., Shoe is to foot as glove is to WHAT? --> "hand") or relation comparison (e.g., Is shoe to foot as glove is to hand? --> "yes"). The RLPFC was engaged more strongly by the comparison subtask relative to completion, suggesting that the RLPFC is particularly involved in comparing relational structures.

  10. Tactile object familiarity in the blind brain reveals the supramodal perceptual-mnemonic nature of the perirhinal cortex

    Directory of Open Access Journals (Sweden)

    Laura eCacciamani

    2016-04-01

    Full Text Available This study is the first to investigate the neural underpinnings of tactile object familiarity in the blind during both perception and memory. In the sighted, the perirhinal cortex (PRC has been implicated in the assessment of visual object familiarity—a crucial everyday task—as evidenced by reduced activation when an object becomes familiar. Here, to examine the PRC’s role in tactile object familiarity in the absence of vision, we trained blind subjects on a unique memory-guided drawing technique and measured brain activity while they perceptually explored raised-line drawings, drew them from tactile memory, and scribbled (control. FMRI before and after a week of training revealed a significant decrease in PRC activation from pre- to post-training (i.e., from unfamiliar to familiar during perceptual exploration as well as memory-guided drawing, but not scribbling. This familiarity-based reduction is the first evidence that the PRC represents tactile object familiarity in the blind. Furthermore, the finding of this effect during both tactile perception and tactile memory provides the critical link in establishing the PRC as a structure whose representations are supramodal for both perception and memory.

  11. The Role of “Mixed” Orexigenic and Anorexigenic Signals and Autoantibodies Reacting with Appetite-Regulating Neuropeptides and Peptides of the Adipose Tissue-Gut-Brain Axis: Relevance to Food Intake and Nutritional Status in Patients with Anorexia Nervosa and Bulimia Nervosa

    Directory of Open Access Journals (Sweden)

    Kvido Smitka

    2013-01-01

    Full Text Available Eating disorders such as anorexia (AN and bulimia nervosa (BN are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY, peptide YY (PYY, cholecystokinin (CCK, leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE, serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice.

  12. The Role of “Mixed” Orexigenic and Anorexigenic Signals and Autoantibodies Reacting with Appetite-Regulating Neuropeptides and Peptides of the Adipose Tissue-Gut-Brain Axis: Relevance to Food Intake and Nutritional Status in Patients with Anorexia Nervosa and Bulimia Nervosa

    Science.gov (United States)

    Papezova, Hana; Vondra, Karel; Hill, Martin; Hainer, Vojtech; Nedvidkova, Jara

    2013-01-01

    Eating disorders such as anorexia (AN) and bulimia nervosa (BN) are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT) peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY), peptide YY (PYY), cholecystokinin (CCK), leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE), serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice. PMID:24106499

  13. Neuropeptide Y: A stressful review.

    Science.gov (United States)

    Reichmann, Florian; Holzer, Peter

    2016-02-01

    Stress is defined as an adverse condition that disturbs the homeostasis of the body and activates adaptation responses. Among the many pathways and mediators involved, neuropeptide Y (NPY) stands out due to its unique stress-relieving, anxiolytic and neuroprotective properties. Stress exposure alters the biosynthesis of NPY in distinct brain regions, the magnitude and direction of this effect varying with the duration and type of stress. NPY is expressed in particular neurons of the brainstem, hypothalamus and limbic system, which explains why NPY has an impact on stress-related changes in emotional-affective behaviour and feeding as well as on stress coping. The biological actions of NPY in mammals are mediated by the Y1, Y2, Y4 and Y5 receptors, Y1 receptor stimulation being anxiolytic whereas Y2 receptor activation is anxiogenic. Emerging evidence attributes NPY a role in stress resilience, the ability to cope with stress. Thus there is a negative correlation between stress-induced behavioural disruption and cerebral NPY expression in animal models of post-traumatic stress disorder. Exogenous NPY prevents the negative consequences of stress, and polymorphisms of the NPY gene are predictive of impaired stress processing and increased risk of neuropsychiatric diseases. Stress is also a factor contributing to, and resulting from, neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's disease, in which NPY appears to play an important neuroprotective role. This review summarizes the evidence for an implication of NPY in stress-related and neurodegenerative pathologies and addresses the cerebral NPY system as a therapeutic target. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Altered Regulation of Protein Kinase A Activity in the Medial Prefrontal Cortex of Normal and Brain-Injured Animals Actively Engaged in a Working Memory Task

    OpenAIRE

    Kobori, Nobuhide; Moore, Anthony N.; Pramod K Dash

    2015-01-01

    Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) signaling is required for short- and long-term memory. In contrast, enhanced PKA activity has been shown to impair working memory, a prefrontal cortex (PFC)-dependent, transient form of memory critical for cognition and goal-directed behaviors. Working memory can be impaired after traumatic brain injury (TBI) in the absence of overt damage to the PFC. The cellular and molecular mechanisms that contribute to this deficit ar...

  15. Oxytocin in the prelimbic medial prefrontal cortex reduces anxiety-like behavior in female and male rats

    OpenAIRE

    2014-01-01

    The neuropeptide oxytocin (OT) has anxiolytic effects in rodents and humans. However, the specific brain regions where OT acts to regulate anxiety requires further investigation. The medial prefrontal cortex (mPFC) has been shown to play a role in the modulation of anxiety-related behavior. In addition, the mPFC contains OT-sensitive neurons, expresses OT receptors, and receives long range axonal projections from OT-producing neurons in the hypothalamus, suggesting that the mPFC may be a targ...

  16. Neuropeptide Y in the Adult and Fetal Human Pineal Gland

    Directory of Open Access Journals (Sweden)

    Morten Møller

    2014-01-01

    Full Text Available Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  17. Neuropeptide Y in the adult and fetal human pineal gland.

    Science.gov (United States)

    Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  18. 350-μm side-view optical probe for imaging the murine brain in vivo from the cortex to the hypothalamus

    Science.gov (United States)

    Kim, Jun Ki; Choi, Jin Woo; Yun, Seok Hyun

    2013-05-01

    Miniature endoscopic probes offer a solution for deep brain imaging by overcoming the limited depth of intravital microscopy. We describe a small-diameter (350 μm) graded-index optical probe with a side-view design for in vivo cellular imaging of the mammalian brain. The side-view probe provides a unique view of the vertical network of neurons and penetrating blood vessels. At a given insertion site, the translational and rotational scanning of the probe provides access to a large tissue area (>) across the cortex, hippocampus, thalamus, and hypothalamus.

  19. Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain

    Directory of Open Access Journals (Sweden)

    Minchenko Dimitri

    2010-04-01

    Full Text Available Abstract Background The Rett Syndrome (RTT brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results Using microarrays and quantitative PCR, the mRNA expression profiles of these two neuroanatomical regions were compared in postmortem brain tissue from RTT patients and normal controls. A subset of genes was differentially expressed in the frontal cortex of RTT brains, some of which are known to be associated with neurological disorders (clusterin and cytochrome c oxidase subunit 1 or are involved in synaptic vesicle cycling (dynamin 1. RNAi-mediated knockdown of MeCP2 in vitro, followed by further expression analysis demonstrated that the same direction of abnormal expression was recapitulated with MeCP2 knockdown, which for cytochrome c oxidase subunit 1 was associated with a functional respiratory chain defect. Chromatin immunoprecipitation (ChIP analysis showed that MeCP2 associated with the promoter regions of some of these genes suggesting that loss of MeCP2 function may be responsible for their overexpression. Conclusions This study has shed more light on the subset of aberrantly expressed genes that result from MECP2 mutations. The mitochondrion has long been implicated in the pathogenesis of RTT, however it has not been at the forefront of RTT research interest since the discovery of MECP2 mutations. The functional consequence of the underexpression of cytochrome c oxidase subunit 1 indicates that this is an area that should be revisited.

  20. Proteomic profiling of brain cortex tissues in a Tau transgenic mouse model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Seong-Hun; Jung, In-Soo; Han, Gi-Yeon; Kim, Nam-Hee; Kim, Hyun-Jung [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Kim, Chan-Wha, E-mail: cwkim@korea.ac.kr [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer A transgenic mouse model expressing NSE-htau23 was used. Black-Right-Pointing-Pointer 2D-gel electrophoresis to analyze the cortex proteins of transgenic mice was used. Black-Right-Pointing-Pointer Differentially expressed spots in different stages of AD were identified. Black-Right-Pointing-Pointer GSTP1 and CAII were downregulated with the progression of AD. Black-Right-Pointing-Pointer SCRN1 and ATP6VE1 were up regulated and down regulated differentially. -- Abstract: Alzheimer's disease (AD) involves regionalized neuronal death, synaptic loss, and an accumulation of intracellular neurofibrillary tangles and extracellular senile plaques. Although there have been numerous studies on tau proteins and AD in various stages of neurodegenerative disease pathology, the relationship between tau and AD is not yet fully understood. A transgenic mouse model expressing neuron-specific enolase (NSE)-controlled human wild-type tau (NSE-htau23), which displays some of the typical Alzheimer-associated pathological features, was used to analyze the brain proteome associated with tau tangle deposition. Two-dimensional electrophoresis was performed to compare the cortex proteins of transgenic mice (6- and 12-month-old) with those of control mice. Differentially expressed spots in different stages of AD were identified with ESI-Q-TOF (electrospray ionization quadruple time-of-flight) mass spectrometry and liquid chromatography/tandem mass spectrometry. Among the identified proteins, glutathione S-transferase P 1 (GSTP1) and carbonic anhydrase II (CAII) were down-regulated with the progression of AD, and secerin-1 (SCRN1) and V-type proton ATPase subunit E 1 (ATP6VE1) were up-regulated only in the early stages, and down-regulated in the later stages of AD. The proteins, which were further confirmed by RT-PCR at the mRNA level and with western blotting at the protein level, are expected to be good candidates as drug targets for AD. The

  1. Electrical brain imaging evidences left auditory cortex involvement in speech and non-speech discrimination based on temporal features

    Directory of Open Access Journals (Sweden)

    Jancke Lutz

    2007-12-01

    Full Text Available Abstract Background Speech perception is based on a variety of spectral and temporal acoustic features available in the acoustic signal. Voice-onset time (VOT is considered an important cue that is cardinal for phonetic perception. Methods In the present study, we recorded and compared scalp auditory evoked potentials (AEP in response to consonant-vowel-syllables (CV with varying voice-onset-times (VOT and non-speech analogues with varying noise-onset-time (NOT. In particular, we aimed to investigate the spatio-temporal pattern of acoustic feature processing underlying elemental speech perception and relate this temporal processing mechanism to specific activations of the auditory cortex. Results Results show that the characteristic AEP waveform in response to consonant-vowel-syllables is on a par with those of non-speech sounds with analogue temporal characteristics. The amplitude of the N1a and N1b component of the auditory evoked potentials significantly correlated with the duration of the VOT in CV and likewise, with the duration of the NOT in non-speech sounds. Furthermore, current density maps indicate overlapping supratemporal networks involved in the perception of both speech and non-speech sounds with a bilateral activation pattern during the N1a time window and leftward asymmetry during the N1b time window. Elaborate regional statistical analysis of the activation over the middle and posterior portion of the supratemporal plane (STP revealed strong left lateralized responses over the middle STP for both the N1a and N1b component, and a functional leftward asymmetry over the posterior STP for the N1b component. Conclusion The present data demonstrate overlapping spatio-temporal brain responses during the perception of temporal acoustic cues in both speech and non-speech sounds. Source estimation evidences a preponderant role of the left middle and posterior auditory cortex in speech and non-speech discrimination based on temporal

  2. Feed intake and brain neuropeptide Y (NPY) and cholecystokinin (CCK) gene expression in juvenile cobia fed plant-based protein diets with different lysine to arginine ratios.

    Science.gov (United States)

    Nguyen, Minh Van; Jordal, Ann-Elise Olderbakk; Espe, Marit; Buttle, Louise; Lai, Hung Van; Rønnestad, Ivar

    2013-07-01

    Cobia (Rachycentron canadum, Actinopterygii, Perciformes;10.5±0.1g) were fed to satiation with three plant-based protein test diets with different lysine (L) to arginine (A) ratios (LL/A, 0.8; BL/A, 1.1; and HL/A, 1.8), using a commercial diet as control for six weeks. The test diets contained 730 g kg(-1) plant ingredients with 505-529 g protein, 90.2-93.9 g lipid kg(-1) dry matter; control diet contained 550 g protein and 95 g lipid kg(-1) dry matter. Periprandial expression of brain NPY and CCK (npy and cck) was measured twice (weeks 1 and 6). At week one, npy levels were higher in pre-feeding than postfeeding cobia for all diets, except LL/A. At week six, npy levels in pre-feeding were higher than in postfeeding cobia for all diets. cck in pre-feeding cobia did not differ from that in postfeeding for all diets, at either time point. Cobia fed LL/A had lower feed intake (FI) than cobia fed BL/A and control diet, but no clear correlations between dietary L/A ratio and FI, growth and expression of npy and cck were detected. The data suggest that NPY serves as an orexigenic factor, but further studies are necessary to describe links between dietary L/A and regulation of appetite and FI in cobia.

  3. Differential adenoassociated virus vector-driven expression of a neuropeptide Y gene in primary rat brain astroglial cultures after transfection with Sendai virosomes versus Lipofectin.

    Science.gov (United States)

    de Fiebre, C M; Wu, P; Notabartolo, D; Millard, W J; Meyer, E M

    1994-06-01

    The ability of Sendai virosomes or Lipofectin to introduce an AAV vector into primary rat brain astroglial cultures was characterized. The pJDT95npy vector was constructed by inserting rat NPY cDNA downstream from the indigenous AAV p5, p19 and p40 promoters in pJDT95. Lipofectin-mediated transfection with pJDT95npy (10 micrograms) resulted in pronounced expression of several NPY mRNA species: p5-driven (3.3 kb), p19-driven (2.7 kb) and p40-driven (0.6, 0.8, 1.1, and 1.8 kb). Exposure to virosomally encapsulated pJDT95npy (50 or 100 ng) resulted in transient expression of some p40-driven mRNA species (0.8 and 1.8 kb). Neither method produced astroglia cells which synthesized mature NPY immunoreactivity. This demonstrates that an AAV-derived vector can drive gene expression in astroglia, that Sendai virosomes can infuse vectors into astroglia, but that the amount of DNA infused in this manner may limit long term expression.

  4. Evolutionary specializations of human association cortex

    NARCIS (Netherlands)

    Mars, R.B.; Passingham, R.E.; Neubert, F.X.; Verhagen, L.; Sallet, J.

    2017-01-01

    Is the human brain a big ape brain? We argue that the human association cortex is larger than would be expected for an equivalent ape brain, suggesting human association cortex is a unique adaptation. The internal organization of the human association cortex shows modifications of the ape plan in

  5. Regulation of neurosteroid biosynthesis by neurotransmitters and neuropeptides

    Directory of Open Access Journals (Sweden)

    Jean-Luc eDo-Rego

    2012-01-01

    Full Text Available The enzymatic pathways leading to the synthesis of bioactive steroids in the brain are now almost completely elucidated in various groups of vertebrates and, during the last decade, the neuronal mechanisms involved in the regulation of neurosteroid production have received increasing attention. This report reviews the current knowledge concerning the effects of neurotransmitters, peptide hormones and neuropeptides on the biosynthesis of neurosteroids. Anatomical studies have been carried out to visualize the neurotransmitter- or neuropeptide-containing fibers contacting steroid-synthesizing neurons as well as the neurotransmitter, peptide hormones or neuropeptide receptors expressed in these neurons. Biochemical experiments have been conducted to investigate the effects of neurotransmitters, peptide hormones or neuropeptides on neurosteroid biosynthesis, and to characterize the type of receptors involved. Thus, it has been found that glutamate, acting through kainate and/or AMPA receptors, rapidly inactivates P450arom, and that melatonin produced by the pineal gland and eye inhibits the biosynthesis of 7-hydroxypregnenolone (7-OH-5P, while prolactin produced by the adenohypophysis enhances the formation of 7-OH-5P. It has also been demonstrated that the biosynthesis of neurosteroids is inhibited by GABA, acting through GABAA receptors, and neuropeptide Y, acting through Y1 receptors. In contrast, it has been shown that the octadecaneuropetide ODN, acting through central-type benzodiazepine receptors, the triakontatetraneuropeptide TTN, acting though peripheral-type benzodiazepine receptors, and vasotocine, acting through V1a-like receptors, stimulate the production of neurosteroids. Since neurosteroids are implicated in the control of various neurophysiological and behavioral processes, these data suggest that some of the neurophysiological effects exerted by neurotransmitters and neuropeptides may be mediated via the regulation

  6. Brain connections of words, perceptions and actions: A neurobiological model of spatio-temporal semantic activation in the human cortex.

    Science.gov (United States)

    Tomasello, Rosario; Garagnani, Max; Wennekers, Thomas; Pulvermüller, Friedemann

    2017-04-01

    Neuroimaging and patient studies show that different areas of cortex respectively specialize for general and selective, or category-specific, semantic processing. Why are there both semantic hubs and category-specificity, and how come that they emerge in different cortical regions? Can the activation time-course of these areas be predicted and explained by brain-like network models? In this present work, we extend a neurocomputational model of human cortical function to simulate the time-course of cortical processes of understanding meaningful concrete words. The model implements frontal and temporal cortical areas for language, perception, and action along with their connectivity. It uses Hebbian learning to semantically ground words in aspects of their referential object- and action-related meaning. Compared with earlier proposals, the present model incorporates additional neuroanatomical links supported by connectivity studies and downscaled synaptic weights in order to control for functional between-area differences purely due to the number of in- or output links of an area. We show that learning of semantic relationships between words and the objects and actions these symbols are used to speak about, leads to the formation of distributed circuits, which all include neuronal material in connector hub areas bridging between sensory and motor cortical systems. Therefore, these connector hub areas acquire a role as semantic hubs. By differentially reaching into motor or visual areas, the cortical distributions of the emergent 'semantic circuits' reflect aspects of the represented symbols' meaning, thus explaining category-specificity. The improved connectivity structure of our model entails a degree of category-specificity even in the 'semantic hubs' of the model. The relative time-course of activation of these areas is typically fast and near-simultaneous, with semantic hubs central to the network structure activating before modality-preferential areas carrying

  7. Neuropeptide signalling systems in flatworms.

    Science.gov (United States)

    McVeigh, P; Kimber, M J; Novozhilova, E; Day, T A

    2005-01-01

    Two distinct families of neuropeptides are known to endow platyhelminth nervous systems - the FMRFamide-like peptides (FLPs) and the neuropeptide Fs (NPFs). Flatworm FLPs are structurally simple, each 4-6 amino acids in length with a carboxy terminal aromatic-hydrophobic-Arg-Phe-amide motif. Thus far, four distinct flatworm FLPs have been characterized, with only one of these from a parasite. They have a widespread distribution within the central and peripheral nervous system of every flatworm examined, including neurones serving the attachment organs, the somatic musculature and the reproductive system. The only physiological role that has been identified for flatworm FLPs is myoexcitation. Flatworm NPFs are believed to be invertebrate homologues of the vertebrate neuropeptide Y (NPY) family of peptides. Flatworm NPFs are 36-39 amino acids in length and are characterized by a caboxy terminal GRPRFamide signature and conserved tyrosine residues at positions 10 and 17 from the carboxy terminal. Like FLPs, NPF occurs throughout flatworm nervous systems, although less is known about its biological role. While there is some evidence for a myoexcitatory action in cestodes and flukes, more compelling physiological data indicate that flatworm NPF inhibits cAMP levels in a manner that is characteristic of NPY action in vertebrates. The widespread expression of these neuropeptides in flatworm parasites highlights the potential of these signalling systems to yield new targets for novel anthelmintics. Although platyhelminth FLP and NPF receptors await identification, other molecules that play pivotal roles in neuropeptide signalling have been uncovered. These enzymes, involved in the biosynthesis and processing of flatworm neuropeptides, have recently been described and offer other distinct and attractive targets for therapeutic interference.

  8. Microglia/monocytes with NG2 expression have no phagocytic function in the cortex after LPS focal injection into the rat brain.

    Science.gov (United States)

    Zhu, Lie; Xiang, Ping; Guo, Kun; Wang, Anni; Lu, Jia; Tay, Samuel Sam Wah; Jiang, Hua; He, Bei Ping

    2012-09-01

    While OX42(+) microglia/macrophages have been considered as a scavenger in the brain, NG2(+) cells are generally considered as oligodendrocyte progenitor cells or function-unknown glial cells. Recent evidence showed that under some pathological conditions, certain cells have become positive for both anti-NG2 and anti-OX42 antibodies. Our results suggested that some OX42(+) microglia or macrophages were induced to express NG2 proteins 3 and 5 days later after focal injection of lipopolysaccharide into the brain cortex of Sprague-Dawley rats. In consideration of the induction of NG2 expression may associate with gaining or losing functions of microglia/macrophages, we further showed that, while OX42(+) or ED1(+) microglia/macrophages presented active phagocytic function, NG2(+) /OX42(+) cells failed to engulf latex beads. The induced expression of NG2 protein may possibly indicate the functional diversity of activated microglia/macrophages in the brain.

  9. Neuropeptide Y protects cerebral cortical neurons by regulating microglial immune function

    Institute of Scientific and Technical Information of China (English)

    Qijun Li; Changzheng Dong; Wenling Li; Wei Bu; Jiang Wu; Wenqing Zhao

    2014-01-01

    Neuropeptide Y has been shown to inhibit the immunological activity of reactive microglia in the rat cerebral cortex, to reduce N-methyl-D-aspartate current (INMDA) in cortical neurons, and protect neurons. In this study, after primary cultured microglia from the cerebral cortex of rats were treated with lipopolysaccharide, interleukin-1β and tumor necrosis factor-α levels in the cell culture medium increased, and mRNA expression of these cytokines also increased. After primary cultured cortical neurons were incubated with the lipopolysaccharide-treated microg-lial conditioned medium, peak INMDA in neurons increased. These effects of lipopolysaccharide were suppressed by neuropeptide Y. After addition of the neuropeptide Y Y1 receptor antago-nist BIBP3226, the effects of neuropeptide Y completely disappeared. These results suggest that neuropeptide Y prevents excessive production of interleukin-1β and tumor necrosis factor-α by inhibiting microglial reactivity. This reduces INMDA in rat cortical neurons, preventing excitotoxic-ity, thereby protecting neurons.

  10. Neurotrophic and antioxidant potential of neuropeptides and trace elements

    Directory of Open Access Journals (Sweden)

    O. A. Gromova

    2015-01-01

    Full Text Available Neurotrophic therapy with brain extract-based drugs has been performed for decades. The basis for their neurotrophic activity is amino acids and neuropeptides. However, incomplete information on the composition of these drugs precludes a detailed description of mechanisms through which their pharmacological effects occur. The review considers the results of the most recent molecular pharmacological investigations and the mechanisms of therapeutic action of cerebrolysin.

  11. Sensory neurobiological analysis of neuropeptide modulation of meal size.

    Science.gov (United States)

    Schwartz, Gary J; Azzara, Anthony V

    2004-08-01

    Gerry Smith's emphasis on the meal as the functional unit of ingestion spurred experiments designed to (1) identify oral and postoral stimuli that affect meal size, and (2) identify peripheral and central neural mechanisms involved in the processing of sensory signals generated by these stimuli. His observations that gut-brain peptides can limit meal size were important in formulating the idea that neuropeptides involved in the control of food intake modulate the peripheral and central neural processing of meal-stimulated sensory signals. This focus on meal size continues to foster the development of hypotheses and the design of experiments that characterize the sites and modes of action of feeding modulatory neuropeptides. These investigations have focused attention on the gut-brain neuraxis as a critical sensory pathway in the control of ingestive behavior, and have revealed important integrative properties of peripheral and central neurons along this axis. The neuromodulatory function of peptides that alter food intake is supported by their ability to recruit the activation of neurons at multiple central nodes of the gut-brain axis and to affect the neural processing and behavioral potency of meal-related gastrointestinal signals important in the negative feedback control of meal size. This sensory neurobiological perspective may also be applied to determine whether feeding modulatory neuropeptides affect the neural and behavioral potency of oral positive feedback signals that promote ingestion.

  12. Neurones and neuropeptides in coelenterates

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Ebbesen, Ditte Graff; McFarlane, I D

    1989-01-01

    The first nervous system probably evolved in coelenterates. Many neurons in coelenterates have morphological characteristics of both sensory and motor neurones, and appear to be multifunctional. Using immunocytochemistry with antisera to the sequence Arg-Phe-NH2 (RFamide), RFamide-like peptides w...... that these neuropeptides play a role in neurotransmission....

  13. Reduced brain-derived neurotrophic factor expression in cortex and hippocampus involved in the learning and memory deficit in molarless SAMP8 mice

    Institute of Scientific and Technical Information of China (English)

    JIANG Qing-song; LIANG Zi-liang; WU Min-Jie; FENG Lin; LIU Li-li; ZHANG Jian-jun

    2011-01-01

    Background The molarless condition has been reported to compromise learning and memory functions. However, it remains unclear how the molarless condition directly affects the central nervous system, and the functional consequences on the brain cortex and hippocampus have not been described in detail. The aim of this study was to find the molecular mechanism related with learning and memory deficit after a bilateral molarless condition having been surgically induced in senescence-accelerated mice/prone8 (SAMP8) mice, which may ultimately provide an experimental basis for clinical prevention of senile dementia.Methods Mice were either sham-operated or subjected to complete molar removal. The animals' body weights were monitored every day. Learning ability and memory were measured in a water maze test at the end of the 1 st, 2nd, and 3rd months after surgery. As soon as significantly prolonged escape latency in the molarless group was detected, the locomotor activity was examined in an open field test. Subsequently, the animals were decapitated and the cortex and hippocampus were dissected for Western blotting to measure the expression levels of brain-derived neurotrophic factor (BDNF) and the tropomyosin related kinase B (TrkB), the high affinity receptor of BDNF.Results Slightly lower weights were consistently observed in the molarless group, but there was no significant difference in weights between the two groups (P>0.05). Compared with the sham group, the molarless group exhibited lengthened escape latency in the water maze test three months after surgery, whereas no difference in locomotor activity was observed. Meanwhile, in the cortex and hippocampus, BDNF levels were significantly decreased in the molarless group (P<0.05); but the expression of its receptor, TrkB, was not significantly affected.Conclusion These results suggested that the molarless condition impaired learning and memory abilities in SAMP8mice three months after teeth extraction, and this

  14. Limbic substrates of the effects of neuropeptide Y on intake of and motivation for palatable food

    NARCIS (Netherlands)

    Pandit, R.; Luijendijk, M.C.; Vanderschuren, L.J.M.J.; la Fleur, S.E.; Adan, R.A.H.

    2014-01-01

    Objective: Neuropeptide Y (NPY), given centrally augments food intake and the motivation to work for palatable food. Here, the brain regions were identified through which NPY increases food intake and motivation. Methods: NPY was infused into three brain regions implicated in food intake and motivat

  15. Limbic substrates of the effects of neuropeptide Y on intake of and motivation for palatable food

    NARCIS (Netherlands)

    Pandit, R.; Luijendijk, M.C.; Vanderschuren, L.J.M.J.; la Fleur, S.E.; Adan, R.A.H.

    2014-01-01

    Objective: Neuropeptide Y (NPY), given centrally augments food intake and the motivation to work for palatable food. Here, the brain regions were identified through which NPY increases food intake and motivation. Methods: NPY was infused into three brain regions implicated in food intake and

  16. Neuropeptide Y (NPY)

    Science.gov (United States)

    Zhang, Kuixing; Rao, Fangwen; Miramontes-Gonzalez, Jose Pablo; Hightower, C. Makena; Vaught, Brian; Chen, Yuhong; Greenwood, Tiffany A.; Schork, Andrew J.; Wang, Lei; Mahata, Manjula; Stridsberg, Mats; Khandrika, Srikrishna; Biswas, Nilima; Fung, Maple M.; Waalen, Jill; Middelberg, Rita P.; Heath, Andrew C.; Montgomery, Grant W.; Martin, Nicholas G.; Whitfield, John B.; Baker, Dewleen G.; Schork, Nicholas J.; Nievergelt, Caroline M.; O’Connor, Daniel T.

    2013-01-01

    Objectives This study sought to understand whether genetic variation at the Neuropeptide Y (NPY) locus governs secretion and stress responses in vivo as well as NPY gene expression in sympathochromaffin cells. Background The NPY is a potent pressor peptide co-released with catecholamines during stress by sympathetic axons. Genome-wide linkage on NPY secretion identified a LOD (logarithm of the odds ratio) peak spanning the NPY locus on chromosome 7p15. Methods Our approach began with genomics (linkage and polymorphism determination), extended into NPY genetic control of heritable stress traits in twin pairs, established transcriptional mechanisms in transfected chromaffin cells, and concluded with observations on blood pressure (BP) in the population. Results Systematic polymorphism tabulation at NPY (by re-sequencing across the locus: promoter, 4 exons, exon/intron borders, and untranslated regions; on 2n = 160 chromosomes of diverse biogeographic ancestries) identified 16 variants, of which 5 were common. We then studied healthy twin/sibling pairs (n = 399 individuals), typing 6 polymorphisms spanning the locus. Haplotype and single nucleotide polymorphism analyses indicated that proximal promoter variant ∇−880Δ (2-bp TG/—, Ins/Del, rs3037354) minor/Δ allele was associated with several heritable (h2) stress traits: higher NPY secretion (h2 = 73 ± 4%) as well as greater BP response to environmental (cold) stress, and higher basal systemic vascular resistance. Association of ∇−880Δ and plasma NPY was replicated in an independent sample of 361 healthy young men, with consistent allelic effects; genetic variation at NPY also associated with plasma NPY in another independent series of 2,212 individuals derived from Australia twin pairs. Effects of allele −880Δ to increase NPY expression were directionally coordinate in vivo (on human traits) and in cells (transfected NPY promoter/luciferase reporter activity). Promoter −880Δ interrupts a novel

  17. Providing and optimizing functional MR (Magnetic Resonance) of motor cortex of human brain by MRI ( Magnetic Resonance Imaging) facilities of Imam Khomeinie Hospital

    CERN Document Server

    Khosravie, H R

    2000-01-01

    During the stimulation, an observable increased signal (%2-%5)in respective sensory-motor cortex was obtained after correcting for partial volume effects, optimizing S/N,and incorporating small vowels. The 2 D F A S T functional image obtained by this method, showed an anatomical association of the increased signal with gray matter of sensory-motor cortex(in T 1 weighted image). The resultant data showed the feasibility of functional magnetic resonance imaging using optimized gradient echo sequences on a standard 1.5 T imager. Display of human brain cortical activity is accomplished using various techniques, by them different spatial and temporal resolution may be obtained. F MRI technique with proper spatial and temporal resolution due to its noninvasivity is one of the promising techniques for detection of brain activities. This can be used as an important tool by neurologists, since a great development has been achieved for display different brain function. This thesis report the results of simulation effe...

  18. Sensing with the Motor Cortex

    OpenAIRE

    Hatsopoulos, Nicholas G.; Suminski, Aaron J.

    2011-01-01

    The primary motor cortex is a critical node in the network of brain regions responsible for voluntary motor behavior. It has been less appreciated, however, that the motor cortex exhibits sensory responses in a variety of modalities including vision and somatosensation. We review current work that emphasizes the heterogeneity in sensori-motor responses in the motor cortex and focus on its implications for cortical control of movement as well as for brain-machine interface development.

  19. Transcriptional responses of the nerve agent-sensitive brain regions amygdala, hippocampus, piriform cortex, septum, and thalamus following exposure to the organophosphonate anticholinesterase sarin

    Directory of Open Access Journals (Sweden)

    Meyerhoff James L

    2011-07-01

    Full Text Available Abstract Background Although the acute toxicity of organophosphorus nerve agents is known to result from acetylcholinesterase inhibition, the molecular mechanisms involved in the development of neuropathology following nerve agent-induced seizure are not well understood. To help determine these pathways, we previously used microarray analysis to identify gene expression changes in the rat piriform cortex, a region of the rat brain sensitive to nerve agent exposure, over a 24-h time period following sarin-induced seizure. We found significant differences in gene expression profiles and identified secondary responses that potentially lead to brain injury and cell death. To advance our understanding of the molecular mechanisms involved in sarin-induced toxicity, we analyzed gene expression changes in four other areas of the rat brain known to be affected by nerve agent-induced seizure (amygdala, hippocampus, septum, and thalamus. Methods We compared the transcriptional response of these four brain regions to sarin-induced seizure with the response previously characterized in the piriform cortex. In this study, rats were challenged with 1.0 × LD50 sarin and subsequently treated with atropine sulfate, 2-pyridine aldoxime methylchloride, and diazepam. The four brain regions were collected at 0.25, 1, 3, 6, and 24 h after seizure onset, and total RNA was processed for microarray analysis. Results Principal component analysis identified brain region and time following seizure onset as major sources of variability within the dataset. Analysis of variance identified genes significantly changed following sarin-induced seizure, and gene ontology analysis identified biological pathways, functions, and networks of genes significantly affected by sarin-induced seizure over the 24-h time course. Many of the molecular functions and pathways identified as being most significant across all of the brain regions were indicative of an inflammatory response. There

  20. Rapid Preconcentration for Liquid Chromatography-Mass Spectrometry Assay of Trace Level Neuropeptides

    Science.gov (United States)

    Zhou, Ying; Mabrouk, Omar S.; Kennedy, Robert T.

    2013-11-01

    Measurement of neuropeptides in the brain through in vivo microdialysis sampling provides direct correlation between neuropeptide concentration and brain function. Capillary liquid chromatography-multistage mass spectrometry (CLC-MSn) has proven to be effective at measuring endogenous neuropeptides in microdialysis samples. In the method, microliter samples are concentrated onto nanoliter volume packed beds before ionization and mass spectrometry analysis. The long times required for extensive preconcentration present a barrier to routine use because of the many samples that must be analyzed and instability of neuropeptides. In this study, we evaluated the capacity of 75 μm inner diameter (i.d.) capillary column packed with 10 μm reversed phase particles for increasing the throughput in CLC-MSn based neuropeptide measurement. Coupling a high injection flow rate for fast sample loading/desalting with a low elution flow rate to maintain detection sensitivity, this column has reduced analysis time from ˜30 min to 3.8 min for 5 μL sample, with 3 pM limit of detection (LOD) for enkephalins and 10 pM LOD for dynorphin A1-8 in 5 μL sample. The use of isotope-labeled internal standard lowered peptide signal variation to less than 5 %. This method was validated for in vivo detection of Leu and Met enkephalin with microdialysate collected from rat globus pallidus. The improvement in speed and stability makes CLC-MSn measurement of neuropeptides in vivo more practical.

  1. Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial.

    Science.gov (United States)

    Aoki, Y; Watanabe, T; Abe, O; Kuwabara, H; Yahata, N; Takano, Y; Iwashiro, N; Natsubori, T; Takao, H; Kawakubo, Y; Kasai, K; Yamasue, H

    2015-04-01

    The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC.

  2. Potencies of antagonists chemically related to iodoproxyfan at histamine H3 receptors in mouse brain cortex and guinea-pig ileum: evidence for H3 receptor heterogeneity?

    Science.gov (United States)

    Schlicker, E; Kathmann, M; Bitschnau, H; Marr, I; Reidemeister, S; Stark, H; Schunack, W

    1996-04-01

    We determined the affinities of 16 newly synthesized H3 receptor antagonists in an H3 receptor binding assay and the potencies of 12 of these compounds at functional H3 receptors in the mouse brain cortex and guinea-pig ileum. The compounds differ from histamine in that the C-C-N side chain is replaced by a chain of the structure C-C-C-O. The two major aims of the study were (1) to investigate whether the two functional H3 receptors are pharmacologically different and (2) to derive structure-activity relationships. The specific binding of 3H-Na-methylhistamine to rat brain cortex membranes was monophasically displaced by each of the 16 compounds at pKi values ranging from 7.30 to 9.48. In superfused mouse brain cortex slices preincubated with 3H-noradrenaline, the electrically evoked tritium overflow was slightly decreased by iodoproxyfan and its deiodo analogue; this effect was counteracted by the H3 receptor antagonist clobenpropit. The other compounds did not affect the evoked tritium overflow by themselves. The concentration-response curve of histamine for its inhibitory effect on the electrically evoked tritium overflow was shifted to the right by the 12 compounds with apparent pA2 values ranging from 7.02 to 9.00. The 12 compounds also shifted to the right the concentration-response curve of R-a-methylhistamine for its inhibitory effect on the electrically induced contraction in guinea-pig ileum strips; the apparent pA2 values ranged from 5.97 to 9.00. Iodoproxyfan decreased the electrically induced contraction by itself and this effect was counteracted by the H3 receptor antagonist thioperamide. The apparent pA2 values in the two functional H3 receptor models showed a highly significant correlation (r = 0.882; P H3 receptor antagonist potency. The two functional H3 receptors in the mouse brain cortex and the guinea-pig ileum may be slightly different; further studies are necessary to clarify whether this difference is due to H3 receptor heterogeneity

  3. Suppression of BDNF-induced expression of neuropeptide Y (NPY) in cortical cultures by oxygen-glucose deprivation: a model system to study ischemic mechanisms in the perinatal brain.

    Science.gov (United States)

    Barnea, Ayalla; Roberts, Jodie

    2002-04-15

    The aim of this study was to establish a culture system that can serve as a model to study hypoxic-ischemic mechanisms regulating the functional expression of NPY neurons in the perinatal brain. Using an aggregate culture system derived from the rat fetal cortex, we defined the effects of oxygen and glucose deprivation on NPY expression, using BDNF-induced production of NPY as a functional criterion. NPY neurons exhibited a differential susceptibility to oxygen and glucose deprivation. Although the neurons could withstand oxygen deprivation for 16 hr, they were dramatically damaged by 8 hr of glucose deprivation and by 1-4 hr of deprivation of both oxygen and glucose (N+Glu-). One-hour exposure to N+Glu- led to a transient inhibition ( approximately 50%) of NPY production manifesting within 24 hr and recovering by 5 days thereafter, a 2-hr exposure to N+Glu- led to a sustained inhibition (50-75%) manifesting 1-5 days thereafter, and a 4-hr exposure to N+Glu- led to a total irreversible suppression of BDNF-induced production of NPY manifesting within 24 hr and lasting 8 days after re-supply of oxygen and glucose. Moreover, 1-hr exposure to N+Glu- led to a substantial and 4-hr exposure led to a total disappearance of immunostaining for MAP-2 and NPY but not for GFAP; indicating that neurons are the primary cell-type damaged by oxygen-glucose deprivation. Analysis of cell viability (LDH, MTT) indicated that progressive changes in cell integrity take place during the 4-hr exposure to N+Glu- followed by massive cell death 24 hr thereafter. Thus, we defined a culture system that can serve as a model to study mechanisms by which ischemic insult leads to suppression and eventually death of NPY neurons. Importantly, changes in NPY neurons can be integrated into the overall scheme of ischemic injury in the perinatal brain.

  4. In vitro evidence that phytanic acid compromises Na(+),K(+)-ATPase activity and the electron flow through the respiratory chain in brain cortex from young rats.

    Science.gov (United States)

    Busanello, Estela Natacha Brandt; Viegas, Carolina Maso; Moura, Alana Pimentel; Tonin, Anelise Miotti; Grings, Mateus; Vargas, Carmen R; Wajner, Moacir

    2010-09-17

    Phytanic acid (Phyt) tissue concentrations are increased in Refsum disease and other peroxisomal disorders characterized by neurologic damage and brain abnormalities. The present work investigated the in vitro effects of Phyt, at concentrations found in these peroxisomal disorders, on important parameters of energy metabolism in brain cortex of young rats. The parameters analyzed were CO(2) production from labeled acetate and glucose, the activities of the citric acid cycle enzymes citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase and malate dehydrogenase, as well as of the respiratory chain complexes I-IV, creatine kinase and Na(+),K(+)-ATPase. Our results show that Phyt did not alter citric acid cycle enzyme activities, or CO(2) production from acetate, reflecting no impairment of the functionality of the citric acid cycle. In contrast, respiratory chain activities were reduced at complexes I, II, I-III, II-III and IV. Membrane synaptical Na(+),K(+)-ATPase activity was also reduced by Phyt, with no alteration of creatine kinase activity. Considering the importance of the electron flow through the respiratory chain for brain energy metabolism (oxidative phosphorylation) and of Na(+),K(+)-ATPase activity for maintaining membrane potential necessary for neurotransmission, the data indicate that Phyt impairs brain bioenergetics at the level of energy formation, as well as neurotransmission. It is presumed that Phyt-induced impairment of these important systems may be involved at least in part in the neurological damage found in patients affected by disorders in which brain Phyt concentrations are increased.

  5. Protective effect of L-Theanine against aluminium induced neurotoxicity in cerebral cortex, hippocampus and cerebellum of rat brain - histopathological, and biochemical approach.

    Science.gov (United States)

    Sumathi, Thangarajan; Shobana, Chandrasekar; Thangarajeswari, Mohan; Usha, Ramakrishnan

    2015-01-01

    L-Theanine is an amino acid derivative primarily found in tea. It has been reported to promote relaxation and have neuroprotective effects. The present study was designed to investigate the role of oxidative stress and the status of antioxidant system in the management of aluminum chloride (AlCl3) induced brain toxicity in various rat brain regions and further to elucidate the potential role of L-Theanine in alleviating such negative effects. Aluminium administration significantly decreased the level of reduced glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, Na(+)/K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase and increased the level of lipid peroxidation and the activities of alkaline phosphatase, acid phosphatase, alanine transaminase and aspartate transaminase in all the brain regions when compared with control rats. Pre-treatment with L-Theanine at a dose of 200 mg/kg b.w. significantly increased the antioxidant status and activities of membrane bound enzymes and also decreased the level of LPO and the activities of marker enzymes, when compared with aluminium induced rats. Aluminium induction also caused histopathological changes in the cerebral cortex, cerebellum and hippocampus of rat brain which was reverted by pretreatment with L-Theanine. The present study clearly indicates the potential of L-Theanine in counteracting the damage inflicted by aluminium on rat brain regions.

  6. The coupling of cerebral blood flow and oxygen metabolism with brain activation is similar for simple and complex stimuli in human primary visual cortex.

    Science.gov (United States)

    Griffeth, Valerie E M; Simon, Aaron B; Buxton, Richard B

    2015-01-01

    Quantitative functional MRI (fMRI) experiments to measure blood flow and oxygen metabolism coupling in the brain typically rely on simple repetitive stimuli. Here we compared such stimuli with a more naturalistic stimulus. Previous work on the primary visual cortex showed that direct attentional modulation evokes a blood flow (CBF) response with a relatively large oxygen metabolism (CMRO2) response in comparison to an unattended stimulus, which evokes a much smaller metabolic response relative to the flow response. We hypothesized that a similar effect would be associated with a more engaging stimulus, and tested this by measuring the primary human visual cortex response to two contrast levels of a radial flickering checkerboard in comparison to the response to free viewing of brief movie clips. We did not find a significant difference in the blood flow-metabolism coupling (n=%ΔCBF/%ΔCMRO2) between the movie stimulus and the flickering checkerboards employing two different analysis methods: a standard analysis using the Davis model and a new analysis using a heuristic model dependent only on measured quantities. This finding suggests that in the primary visual cortex a naturalistic stimulus (in comparison to a simple repetitive stimulus) is either not sufficient to provoke a change in flow-metabolism coupling by attentional modulation as hypothesized, that the experimental design disrupted the cognitive processes underlying the response to a more natural stimulus, or that the technique used is not sensitive enough to detect a small difference. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Chronic corticosterone decreases brain-derived neurotrophic factor (BDNF) mRNA and protein in the hippocampus, but not in the frontal cortex, of the rat.

    Science.gov (United States)

    Jacobsen, Jacob P R; Mørk, Arne

    2006-09-19

    This study examined the effects of chronic corticosterone (32 mg/kg/day, s.c., 21 days) on brain-derived neurotrophic factor (BDNF) mRNA and protein in the frontal cortex and hippocampus of the rat. Because evidence suggests that BDNF is an important determinant of the function of the 5-hydroxytryptamine (5-HT) system, we also quantified tissue levels of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), to investigate if changes in BDNF mRNA and protein paralleled changes in the 5-HT system. Corticosterone modestly decreased BDNF protein (-16.6%) in whole hippocampus and BDNF mRNA (-19%) in the CA3 area. In contrast, BDNF mRNA and protein in the frontal cortex were unchanged. In both the frontal cortex and hippocampus, tissue levels of 5-HT and 5-HIAA were increased and decreased, respectively. Combined, these data suggests that the effects of corticosterone on the BDNF system are not linked to the effects on the 5-HT systems. However, our findings do suggest that chronic corticosterone impairs hippocampal BDNF function, a finding with potential relevance for the hippocampal atrophy reported in major depression. Additionally, as inferred from the alterations in tissue levels of 5-HT and 5-HIAA, chronic corticosterone may influence the function of the 5-HT system.

  8. Expression of TrkB and TrkC but not BDNF mRNA in neurochemically identified interneurons in rat visual cortex in vivo and in organotypic cultures.

    Science.gov (United States)

    Gorba, T; Wahle, P

    1999-04-01

    The mammalian visual cortex contains morphologically diverse populations of interneurons whose neurochemical properties are believed to be regulated by neurotrophic factors. This requires the expression of neurotrophin receptors. We have analysed whether brain-derived neurotrophic factor (BDNF), its receptor trkB and the NT-3 receptor trkC are expressed in interneurons of rat visual cortex in vivo, and in organotypic visual cortex cultures, paying particular attention to the subsets of neuropeptidergic neurons. In situ hybridization in combination with immunofluorescence for calcium-binding proteins and neuropeptides revealed that BDNF is not expressed in interneurons in vivo or in vitro. For the neurotrophin receptors we found in vivo at postnatal day 70 (P70) that approximately 80% of the parvalbumin-immunoreactive (-ir), but only 50% of the intensely calbindin-ir, and only 20% of the calretinin-ir neurons express trkB. Double labelling with neuropeptides revealed that approximately 50% of the neuropeptide Y-ir and approximately 50% of the somatostatin-ir neurons express trkB in a laminar-specific way. Only 25% of the vasoactive intestinal polypeptide (VIP)-ir neurons coexpress trkB. The coexpression of neuropeptide Y with trkB, but not with BDNF or trkC, was confirmed with a double in situ hybridization. In contrast, the percentages differed in the immature cortex; at P14 70% of the NPY-ir neurons and 46% of the calretinin-ir neurons revealed trkB expression, while the ratio for calbindin-ir cells was fairly constant (59%). From the interneuron populations studied, only 12% of the parvalbumin-ir neurons expressed trkC. A triple labelling revealed that some neurons coexpressed both trk mRNAs, while others had only trkC. The analysis of interneurons in organotypic cultures yielded very similar results. The results indicate that trkB ligands synthesized by pyramidal neurons influence neuropeptide or calcium-binding protein expression in a paracrine or transsynaptic

  9. Effect of chronic intermittent hypoxia on the expression of Nip3, cell apoptosis, β-amyloid protein deposit in mice brain cortex

    Institute of Scientific and Technical Information of China (English)

    ZENG Yi-ming; CAI Kai-jin; CHEN Xiao-yong; WU Minx-ia; LIN Xi

    2009-01-01

    Background Chronic intermittent hypoxia (CIH) is the most important pathophysiologic feature of sleep apnea syndrome (SAS). To explore the relationship between SAS and dementia, the effects of CIH on the expression of Nip3, neuron apoptosis andβ-amyloid protein deposit in the brain cortex of the frontal lobe of mice were evaluated in this study. Methods Thirty male ICR mice were divided into four groups: control group (A, n=-10, sham hypoxia/reoxygenation), 2 weeks CIH group (B, n=-5), 4 weeks CIH group (C, n=-5), and 8 weeks CIH group (D, n=10). The ICR mice were placed in a chamber and exposed to intermittent hypoxia (oxygen concentration changed periodically from (21.72±0.55)% to (6.84±0.47)% every two minutes, eight hours per day). Neuron apoptosis of the cortex of the frontal lobe was detected by means of terminal deoxy-nucleotidyl transferase-mediated in situ end labeling (TUNEL). Immunohistochemical staining was performed for measuring expression of Nip3 and β-amyloid protein. The ultrastructure of neurons was observed under a transmission electron microscope. Results TUNEL positive neurons in each square millimeter in the cortex of the frontal lobe were categorized by median or Ri into group A (1,5.5), group B (133, 13), group C (252, 21), and group D (318, 24). There were significant differences among the above four groups (P=0.000). The significance test was performed between the control group and each CIH group respectively: group A and B (P>0.05); group A and C (P 0.05); groups A and C (P<0.005); and groups A and D (P<0.005). There was no significant difference between groups B and C, groups B and D, and groups C and D. The expression of Nip3 was closely correlated with neuron apoptosis in the brain (P <0.05). The expression ofβ-amyloid protein in the brain of mice was negative in all CIH groups and the control group. Ultrastructure observation showed karyopyknosis of nucleus, swelling of chondriosomes, deposit of lipofuscins and degeneration of

  10. Nematode neuropeptides as transgenic nematicides.

    Science.gov (United States)

    Warnock, Neil D; Wilson, Leonie; Patten, Cheryl; Fleming, Colin C; Maule, Aaron G; Dalzell, Johnathan J

    2017-02-01

    Plant parasitic nematodes (PPNs) seriously threaten global food security. Conventionally an integrated approach to PPN management has relied heavily on carbamate, organophosphate and fumigant nematicides which are now being withdrawn over environmental health and safety concerns. This progressive withdrawal has left a significant shortcoming in our ability to manage these economically important parasites, and highlights the need for novel and robust control methods. Nematodes can assimilate exogenous peptides through retrograde transport along the chemosensory amphid neurons. Peptides can accumulate within cells of the central nerve ring and can elicit physiological effects when released to interact with receptors on adjoining cells. We have profiled bioactive neuropeptides from the neuropeptide-like protein (NLP) family of PPNs as novel nematicides, and have identified numerous discrete NLPs that negatively impact chemosensation, host invasion and stylet thrusting of the root knot nematode Meloidogyne incognita and the potato cyst nematode Globodera pallida. Transgenic secretion of these peptides from the rhizobacterium, Bacillus subtilis, and the terrestrial microalgae Chlamydomonas reinhardtii reduce tomato infection levels by up to 90% when compared with controls. These data pave the way for the exploitation of nematode neuropeptides as a novel class of plant protective nematicide, using novel non-food transgenic delivery systems which could be deployed on farmer-preferred cultivars.

  11. Neuropeptide S receptor gene -- converging evidence for a role in panic disorder.

    Science.gov (United States)

    Domschke, K; Reif, A; Weber, H; Richter, J; Hohoff, C; Ohrmann, P; Pedersen, A; Bauer, J; Suslow, T; Kugel, H; Heindel, W; Baumann, C; Klauke, B; Jacob, C; Maier, W; Fritze, J; Bandelow, B; Krakowitzky, P; Rothermundt, M; Erhardt, A; Binder, E B; Holsboer, F; Gerlach, A L; Kircher, T; Lang, T; Alpers, G W; Ströhle, A; Fehm, L; Gloster, A T; Wittchen, H-U; Arolt, V; Pauli, P; Hamm, A; Deckert, J

    2011-09-01

    Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn¹⁰⁷Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case-control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli.

  12. Can neuropeptides treat obesity? A review of neuropeptides and their potential role in the treatment of obesity.

    Science.gov (United States)

    Boughton, C K; Murphy, K G

    2013-12-01

    Obesity is a major worldwide public health issue. The physiological systems that regulate body weight are thus of great interest as targets for anti-obesity agents. Peptidergic systems are critical to the regulation of energy homeostasis by key regions in the hypothalamus and brainstem. A number of neuropeptide systems have therefore been investigated as potential treatments for obesity. Blocking orexigenic peptide signals such as neuropeptide Y, melanin-concentrating hormone, orexins, relaxin-3 and galanin-like peptide or stimulating anorectic signalling pathways used by peptides such as the melanocortins, ciliary neurotrophic factor and brain-derived neurotrophic factor, are approaches that have shown some promise, but which have also highlighted possible concerns. Manipulation of central peptidergic systems poses a number of therapeutic problems, including brain access and side effects. Given that the homeostatic defence of body weight may limit the effectiveness of any single-target therapy developed, a combination therapy approach may offer the best hope for the effective prevention and treatment of obesity. This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  13. Synchronous changes of cortical thickness and corresponding white matter microstructure during brain development accessed by diffusion MRI tractography from parcellated cortex

    Directory of Open Access Journals (Sweden)

    Tina eJeon

    2015-12-01

    Full Text Available Cortical thickness (CT changes during normal brain development is associated with complicated cellular and molecular processes including synaptic pruning and apoptosis. In parallel, the microstructural enhancement of developmental white matter (WM axons with their neuronal bodies in the cerebral cortex has been widely reported with measurements of metrics derived from diffusion tensor imaging (DTI, especially fractional anisotropy (FA. We hypothesized that the changes of CT and microstructural enhancement of corresponding axons are highly interacted during development. DTI and T1-weighted images of 50 healthy children and adolescents between the ages of 7 to 25 years were acquired. With the parcellated cortical gyri transformed from T1-weighted images to DTI space as the tractography seeds, probabilistic tracking was performed to delineate the WM fibers traced from specific parcellated cortical regions. CT was measured at certain cortical regions and FA was measured from the WM fibers traced from same cortical regions. The CT of all frontal cortical gyri, includeing Brodmann areas 4, 6, 8, 9, 10, 11, 44, 45, 46 and 47, decreased significantly and heterogeneously; concurrently, significant and heterogeneous increases of FA of WM traced from corresponding regions were found. We further revealed significant correlation between the slopes of the CT decrease and the slopes of corresponding WM FA increase in all frontal cortical gyri, suggesting coherent cortical pruning and corresponding WM microstructural enhancement. Such correlation was not found in cortical regions other than frontal cortex. The molecular and cellular mechanisms of these synchronous changes may be associated with overlapping signaling pathways of axonal guidance, synaptic pruning, neuronal apoptosis and more prevalent interstitial neurons in the prefrontal cortex. Revealing the coherence of cortical and WM structural changes during development may open a new window for

  14. Biochemical characterisation and clinical correlation of neuropeptides in neuroblastoma with emphasis on neuropeptide Y

    OpenAIRE

    Bjellerup, Per

    2000-01-01

    Neuropeptides influence cellular events involved in tumour growth and differentiation. Neuroblastoma, a malignant childhood tumour of neural crest origin, synthesises and releases monoamines and neuropeptides. The concentrations of some of these neuropeptides in plasma are correlated to clinical stage and outcome. The neuropeptides exist in various molecular forms in plasma and tumour tissue but their biochemical structure in vivo are poorly investigated. The aim of the ...

  15. Epigenetic control of cancer by neuropeptides

    Science.gov (United States)

    Galoian, Karina; Patel, Parthik

    2017-01-01

    Neuropeptides act as neurohormones, neurotransmitters and/or neuromodulators. Neuropeptides maintain physiological homeostasis and are paramount in molecular mechanisms of disease progression and regulation, including in cancer. Neuropeptides, by their definition, originate and are secreted from the neuronal cells, they are able to signal to neighboring cells or are released into the blood flow, if they act as neurohormones. The majority of neuropeptides exert their functions through G protein-coupled receptors, with certain exceptions. Although previous studies indicate that neuropeptides function in supporting proliferation of malignant cells in many types of solid tumor, the antitumorigenic action of the neuropeptides and their receptors, for example, in gastric cancers and chondrosarcoma, were also reported. It is known that epigenetically modified chromatin regulates molecular mechanisms involved in gene expression and malignant progression. The epigenetic modifications are genetically heritable, although they do not cause changes in DNA sequence. DNA methylation, histone modifications and miRNA expression are subject to those modifications. While there is substantial data on epigenetic regulation of neuropeptides, the epigenetic control of cancer by neuropeptides is considered to be uncharted territory. The aim of the current review is to describe the involvement of neuropeptides in the epigenetic machinery of cancer based on data obtained from our laboratory and from other authors.

  16. [Morphological and laminar distribution of cholecystokinin-immunoreactive neurons in cortex of human inferior parietal lobe and their clinical significance].

    Science.gov (United States)

    Puskas, Laslo; Draganić-Gajić, Saveta; Malobabić, Slobodan; Puskas, Nela; Krivokuća, Dragan; Stanković, Gordana

    2008-01-01

    Cholecystocinine is a neuropeptide whose function in the cortex has not yet been clarified, although its relation with some psychic disorders has been noticed. Previous studies have not provided detailed data about types, or arrangement of neurons that contain those neuropeptide in the cortex of human inferior parietal lobe. The aim of this study was to examine precisely the morphology and typography of neurons containing cholecytocinine in the human cortex of inferior parietal lobule. There were five human brains on which we did the immunocystochemical research of the shape and laminar distribution of cholecystocinine immunoreactive neurons on serial sections of supramarginal gyrus and angular gyrus. The morphological analysis of cholecystocinine-immunoreactive neurons was done on frozen sections using avidin-biotin technique, by antibody to cholecystocinine diluted in the proportion 1:6000 using diamine-benzedine. Cholecystocinine immunoreactive neurons were found in the first three layers of the cortex of inferior parietal lobule, and their densest concentration was in the 2nd and 3rd layer. The following types of neurons were found: bipolar neurons, then its fusiform subtype, Cajal-Retzius neurons (in the 1st layer), reverse pyramidal (triangular) and unipolar neurons. The diameters of some types of neurons were from 15 to 35 microm, and the diameters of dendritic arborization were from 85-207 microm. A special emphasis is put on the finding of Cajal-Retzius neurons that are immunoreactive to cholecystocinine, which demands further research. Bearing in mind numerous clinical studies pointing out the role of cholecystokinine in the pathogenesis of schizophrenia, the presence of a great number of cholecystokinine immunoreactive neurons in the cortex of inferior parietal lobule suggests their role in the pathogenesis of schizophrenia.

  17. Morphological and laminar distribution of cholescystokinine - immunoreactive neurons in cortex of human inferior parietal lobule and their clinical significance

    Directory of Open Access Journals (Sweden)

    Puškaš Laslo

    2008-01-01

    Full Text Available Introduction. Cholecystocinine is a neuropeptide whose function in the cortex has not yet been clarified, although its relation with some psychic disorders has been noticed. Previous studies have not provided detailed data about types, or arrangement of neurons that contain those neuropeptide in the cortex of human inferior parietal lobe. The aim of this study was to examine precisely the morphology and typography of neurons containing cholecytocinine in the human cortex of inferior parietal lobule. Material and methods. There were five human brains on which we did the immunocystochemical research of the shape and laminar distribution of cholecystocinine immunoreactive neurons on serial sections of supramarginal gyrus and angular gyrus. The morphological analysis of cholecystocinine-immunoreactive neurons was done on frozen sections using avidin-biotin technique, by antibody to cholecystocinine diluted in the proportion 1:6000 using diamine-benzedine. Results. Cholecystocinine immunorective neurons were found in the first three layers of the cortex of inferior parietal lobule, and their densest concentration was in the 2nd and 3rd layer. The following types of neurons were found: bipolar neurons, then its fusiform subtype, Cajal-Retzius neurons (in the 1st layer, reverse pyramidal (triangular and unipolar neurons. The diameters of some types of neurons were from 15 to 35 µm, and the diameters of dendritic arborization were from 85-207 µm. A special emphasis is put on the finding of Cajal-Retzius neurons that are immunoreactive to cholecystocinine, which demands further research. Conclusion. Bearing in mind numerous clinical studies pointing out the role of cholecystokinine in the pathogenesis of schizophrenia, the presence of a great number of cholecystokinine immunoreactive neurons in the cortex of inferior parietal lobule suggests their role in the pathogenesis of schizophrenia.

  18. Differences in the molecular structure of the blood-brain barrier in the cerebral cortex and white matter: an in silico, in vitro, and ex vivo study.

    Science.gov (United States)

    Nyúl-Tóth, Ádám; Suciu, Maria; Molnár, Judit; Fazakas, Csilla; Haskó, János; Herman, Hildegard; Farkas, Attila E; Kaszaki, József; Hermenean, Anca; Wilhelm, Imola; Krizbai, István A

    2016-06-01

    The blood-brain barrier (BBB) is the main interface controlling molecular and cellular traffic between the central nervous system (CNS) and the periphery. It consists of cerebral endothelial cells (CECs) interconnected by continuous tight junctions, and closely associated pericytes and astrocytes. Different parts of the CNS have diverse functions and structures and may be subject of different pathologies, in which the BBB is actively involved. It is largely unknown, however, what are the cellular and molecular differences of the BBB in different regions of the brain. Using in silico, in vitro, and ex vivo techniques we compared the expression of BBB-associated genes and proteins (i.e., markers of CECs, brain pericytes, and astrocytes) in the cortical grey matter and white matter. In silico human database analysis (obtained from recalculated data of the Allen Brain Atlas), qPCR, Western blot, and immunofluorescence studies on porcine and mouse brain tissue indicated an increased expression of glial fibrillary acidic protein in astrocytes in the white matter compared with the grey matter. We have also found increased expression of genes of the junctional complex of CECs (occludin, claudin-5, and α-catenin) in the white matter compared with the cerebral cortex. Accordingly, occludin, claudin-5, and α-catenin proteins showed increased expression in CECs of the white matter compared with endothelial cells of the cortical grey matter. In parallel, barrier properties of white matter CECs were superior as well. These differences might be important in the pathogenesis of diseases differently affecting distinct regions of the brain.

  19. Quantitative Neuropeptidome Analysis Reveals Neuropeptides Are Correlated with Social Behavior Regulation of the Honeybee Workers.

    Science.gov (United States)

    Han, Bin; Fang, Yu; Feng, Mao; Hu, Han; Qi, Yuping; Huo, Xinmei; Meng, Lifeng; Wu, Bin; Li, Jianke

    2015-10-01

    Neuropeptides play vital roles in orchestrating neural communication and physiological modulation in organisms, acting as neurotransmitters, neuromodulators, and neurohormones. The highly evolved social structure of honeybees is a good system for understanding how neuropeptides regulate social behaviors; however, much knowledge on neuropeptidomic variation in the age-related division of labor remains unknown. An in-depth comparison of the brain neuropeptidomic dynamics over four time points of age-related polyethism was performed on two strains of honeybees, the Italian bee (Apis mellifera ligustica, ITb) and the high royal jelly producing bee (RJb, selected for increasing royal jelly production for almost four decades from the ITb in China). Among the 158 identified nonredundant neuropeptides, 77 were previously unreported, significantly expanding the coverage of the honeybee neuropeptidome. The fact that 14 identical neuropeptide precursors changed their expression levels during the division of labor in both the ITb and RJb indicates they are highly related to task transition of honeybee workers. These observations further suggest the two lines of bees employ a similar neuropeptidome modification to tune their respective physiology of age polyethism via regulating excretory system, circadian clock system, and so forth. Noticeably, the enhanced level of neuropeptides implicated in regulating water homeostasis, brood pheromone recognition, foraging capacity, and pollen collection in RJb signify the fact that neuropeptides are also involved in the regulation of RJ secretion. These findings gain novel understanding of honeybee neuropeptidome correlated with social behavior regulation, which is potentially important in neurobiology for honeybees and other insects.

  20. The endoparasitoid, Cotesia vestalis, regulates host physiology by reprogramming the neuropeptide transcriptional network.

    Science.gov (United States)

    Shi, Min; Dong, Shuai; Li, Ming-tian; Yang, Yan-yan; Stanley, David; Chen, Xue-xin

    2015-02-02

    Endoparasitoids develop inside another insect by regulating host immunity and development via maternal factors injected into hosts during oviposition. Prior results have provided insights into parasitism-induced immunosuppression, including the neuropeptide accumulation in parasitized insects. Nonetheless, our understanding of neuropeptide influence on host development and behavior is not yet complete. We posed the hypothesis that parasitization alters expression of genes encoding pro-neuropeptides and used larvae of Plutella xylostella and its endoparasitoid, Cotesia vestalis to test our hypothesis. We prepared transcriptomes from the larval P. xylostella brain-CC-CA complex and identified transcripts encoding 19 neuropeptides. All corresponding cDNAs were confirmed by RACE. Our results demonstrate that parasitism significantly down-regulated, or delayed, expression of genes encoding pro-neuropeptides within 48 h post-parasitization. Changing expression of these genes may account for the previously reported decreased feeding behavior, reduced growth rates and aborted development in the host larvae. In effect, parasitization may operate at the molecular level within the CNS to create global changes in larval host biology. The significance of our finding is that, in addition to the known effects on immunity, parasitoids influence host pro-neuropeptide gene transcription. This finding reveals a new mechanism operating in host-parasitoid relationships to the advantage of the parasitoid.

  1. Long-term effects of cholinergic basal forebrain lesions on neuropeptide Y and somatostatin immunoreactivity in rat neocortex

    NARCIS (Netherlands)

    Gaykema, R.P.A.; Compaan, J.C.; Nyakas, C.; Horvath, E.; Luiten, P.G.M.

    1989-01-01

    The effect of cholinergic basal forebrain lesions on immunoreactivity to somatostatin (SOM-i) and neuropeptide-Y (NPY-i) was investigated in the rat parietal cortex, 16-18 months after multiple bilateral ibotenic acid injections in the nucleus basalis complex. As a result of the lesion, the choliner

  2. Role of neuropeptide FF in central cardiovascular and neuroendocrine regulation.

    Science.gov (United States)

    Jhamandas, Jack H; Goncharuk, Valeri

    2013-01-01

    Neuropeptide FF (NPFF) is an octapeptide belonging to the RFamide family of peptides that have been implicated in a wide variety of physiological functions in the brain including central cardiovascular and neuroendocrine regulation. The effects of these peptides are mediated via NPFF1 and NPFF2 receptors that are abundantly expressed in the rat and human brain. Herein, we review evidence for the role of NPFF in central regulation of blood pressure particularly within the brainstem and the hypothalamic paraventricular nucleus (PVN). At a cellular level, NPFF demonstrates distinct responses in magnocellular and parvocellular neurons of the PVN, which regulate the secretion of neurohypophyseal hormones and sympathetic outflow, respectively. Finally, the presence of NPFF system in the human brain and its alterations within the hypertensive brain are discussed.

  3. Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate

    Energy Technology Data Exchange (ETDEWEB)

    Michaelides, M.; Wang, G.; Michaelides, M.; Pascau, J.; Gispert, J.-D.; Delis, F.; Grandy, D.K.; Wang, G.-J.; Desco, M.; Rubinstein, M.; Volkow, N.D.; Thanos, P.K.

    2010-07-16

    Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated image registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.

  4. Comparative distribution of central neuropeptide Y (NPY) in the prairie (Microtus ochrogaster) and meadow (M. pennsylvanicus) vole.

    Science.gov (United States)

    Hostetler, Caroline M; Hitchcock, Leah N; Anacker, Allison M J; Young, Larry J; Ryabinin, Andrey E

    2013-02-01

    Neuropeptide Y (NPY) has been implicated as a modulator of social behavior, often in a species-specific manner. Comparative studies of closely related vole species are particularly useful for identifying neural systems involved in social behaviors in both voles and humans. In the present study, immunohistochemistry was performed to compare NPY-like immunoreactivity (-ir) in brain tissue of the socially monogamous prairie vole and non-monogamous meadow vole. Species differences in NPY-ir were observed in a number of regions including the cortex, extended amygdala, septal area, suprachiasmatic nucleus, and intergeniculate leaf. Meadow voles had higher NPY-ir in all these regions as compared to prairie voles. No differences were observed in the striatum or hippocampus. The extended amygdala and lateral septum are regions that play a key role in regulation of monogamous behaviors such as pair bonding and paternal care. The present study suggests NPY in these regions may be an additional modulator of these species-specific social behaviors. Meadow voles had moderately higher NPY-ir in a number of hypothalamic regions, especially in the suprachiasmatic nucleus. Meadow voles also had much higher levels of NPY-ir in the intergeniculate leaflet, another key region in the regulation of circadian rhythms. Overall, species differences in NPY-ir were observed in a number of brain regions implicated in emotion, stress, circadian, and social behaviors. These findings provide additional support for a role for the NPY system in species-typical social behaviors.

  5. Changes in serotonin (5-HT) and brain-derived neurotrophic factor (BDFN) expression in frontal cortex and hippocampus of aged rat treated with high tryptophan diet.

    Science.gov (United States)

    Musumeci, Giuseppe; Castrogiovanni, Paola; Castorina, Sergio; Imbesi, Rosa; Szychlinska, Marta Anna; Scuderi, Soraya; Loreto, Carla; Giunta, Salvatore

    2015-10-01

    Age-related cognitive decline is accompanied by an alteration in neurotransmitter synthesis and a dysregulation of neuroplasticity-related molecules such as serotonin (5-HT) and brain-derived neurotrophic factor (BDFN). It has been previously demonstrated that hyperserotonemia induced by l-Tryptophan (TrP) enriched diet protect against memory deficits during physiological aging. Since 5-HT is closely associated to BDNF, we aimed to investigate the effect of high TrP diet on 5-HT levels and BDNF expression in Frontal Cortex (FC) and Hippocampus (Hp) of aged rats. We found that the raising of systemic 5-HT levels by chronic diet (1 month) containing high TrP significantly prevents age-related decline of BDNF protein expression in both brain areas as indicated by ELISA and Western Blot analyses. Interestingly, immunohistochemical analyses confirmed that high TrP diet significantly elevates the number of 5-HT immunoreactive fibers in both brain areas tested and this correlated with BDNF increase in the FC and hippocampal regions CA1, CA2, CA3 and a strikingly down-regulation of neurotrophin levels in the dentate gyrus (DG) of aged rats. Altogether, these finding provide evidence that enhanced TrP intake and the consequent increase in 5-HT neurotransmission may act as a modulator of BDNF system suggesting a possible mechanism for the protective role of serotonergic system on memory impairment occurring along normal aging process.

  6. Effect of Transcranial Magnetic Stimulation on the Expression of c-Fos and Brain-derived Neurotrophic Factor of the Cerebral Cortex in Rats with Cerebral Infarct

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiaoqiao; MEI Yuanwu; LIU Chuanyu; YU Shanchun

    2007-01-01

    The effect of transcranial magnetic stimulation (TMS) on the neurological functional recovery and expression of c-Fos and brain-derived neurotrophic factor (BDNF) of the cerebral cortex in rats with cerebral infarction was investigated. Cerebral infarction models were established by using left middle cerebral artery occlusion (MCAO) and were randomly divided into a model group (n=40) and a TMS group (n=40). TMS treatment (2 times per day, 30 pulses per time) with a frequency of 0.5 Hz and magnetic field intensity of 1.33 Tesla was carried out in TMS group after MCAO. Modified neurological severity score (NSS) were recorded before and 1, 7, 14, 21, and 28 day(s) after MCAO. The expression of c-Fos and BDNF was immunohistochemically detected 1, 7,14, 21, and 28 day(s) after infarction respectively. Our results showed that a significant recovery of NSS (P<0.05) was found in animals treated by TMS on day 7, 14, 21, and 28 as compared with the animals in the model group. The positive expression of c-Fos and BDNF was detected in the cortex surrounding the infarction areas, while the expression of c-Fos and BDNF increased significantly in TMS treatment group in comparison with those in model group 7, 14, 21, and 28 days (P<0.05) and 7,14, 21 days (P<0.01) after infarction, respectively. It is concluded that TMS has therapeutic effect on cerebral infarction and this may have something to do with TMS's ability to promote the expression of c-Fos and BDNF of the cerebral cortex in rats with cerebral infarction.

  7. Distinct transcriptome expression of the temporal cortex of the primate Microcebus murinus during brain aging versus Alzheimer's disease-like pathology.

    Directory of Open Access Journals (Sweden)

    Ronza Abdel Rassoul

    Full Text Available Aging is the primary risk factor of neurodegenerative disorders such as Alzheimer's disease (AD. However, the molecular events occurring during brain aging are extremely complex and still largely unknown. For a better understanding of these age-associated modifications, animal models as close as possible to humans are needed. We thus analyzed the transcriptome of the temporal cortex of the primate Microcebus murinus using human oligonucleotide microarrays (Affymetrix. Gene expression profiles were assessed in the temporal cortex of 6 young adults, 10 healthy old animals and 2 old, "AD-like" animals that presented ß-amyloid plaques and cortical atrophy, which are pathognomonic signs of AD in humans. Gene expression data of the 14,911 genes that were detected in at least 3 samples were analyzed. By SAM (significance analysis of microarrays, we identified 47 genes that discriminated young from healthy old and "AD-like" animals. These findings were confirmed by principal component analysis (PCA. ANOVA of the expression data from the three groups identified 695 genes (including the 47 genes previously identified by SAM and PCA with significant changes of expression in old and "AD-like" in comparison to young animals. About one third of these genes showed similar changes of expression in healthy aging and in "AD-like" animals, whereas more than two thirds showed opposite changes in these two groups in comparison to young animals. Hierarchical clustering analysis of the 695 markers indicated that each group had distinct expression profiles which characterized each group, especially the "AD-like" group. Functional categorization showed that most of the genes that were up-regulated in healthy old animals and down-regulated in "AD-like" animals belonged to metabolic pathways, particularly protein synthesis. These data suggest the existence of compensatory mechanisms during physiological brain aging that disappear in "AD-like" animals. These results open

  8. An indirect action contributes to c-fos induction in paraventricular hypothalamic nucleus by neuropeptide Y

    Science.gov (United States)

    Neuropeptide Y (NPY) is a well-established orexigenic peptide and hypothalamic paraventricular nucleus (PVH) is one major brain site that mediates the orexigenic action of NPY. NPY induces abundant expression of C-Fos, an indicator for neuronal activation, in the PVH, which has been used extensively...

  9. Neuropeptide-like precursor 4 is uniquely expressed during pupal diapause in the flesh fly

    Science.gov (United States)

    Suppression subtractive hybridization comparing brains from diapausing and nondiapausing pupae of the flesh fly, Sarcophaga crassipalpis, suggested that the gene encoding neuropeptide-like precursor 4 (Nplp4) was uniquely expressed during diapause. We have sequenced the full-length cDNA encoding Npl...

  10. Current trends in intraoperative optical imaging for functional brain mapping and delineation of lesions of language cortex.

    Science.gov (United States)

    Prakash, Neal; Uhlemann, Falk; Sheth, Sameer A; Bookheimer, Susan; Martin, Neil; Toga, Arthur W

    2009-08-01

    Resection of a cerebral arteriovenous malformation (AVM), epileptic focus, or glioma, ideally has a prerequisite of microscopic delineation of the lesion borders in relation to the normal gray and white matter that mediate critical functions. Currently, Wada testing and functional magnetic resonance imaging (fMRI) are used for preoperative mapping of critical function, whereas electrical stimulation mapping (ESM) is used for intraoperative mapping. For lesion delineation, MRI and positron emission tomography (PET) are used preoperatively, whereas microscopy and histological sectioning are used intraoperatively. However, for lesions near eloquent cortex, these imaging techniques may lack sufficient resolution to define the relationship between the lesion and language function, and thus not accurately determine which patients will benefit from neurosurgical resection of the lesion without iatrogenic aphasia. Optical techniques such as intraoperative optical imaging of intrinsic signals (iOIS) show great promise for the precise functional mapping of cortices, as well as delineation of the borders of AVMs, epileptic foci, and gliomas. Here we first review the physiology of neuroimaging, and then progress towards the validation and justification of using intraoperative optical techniques, especially in relation to neurosurgical planning of resection AVMs, epileptic foci, and gliomas near or in eloquent cortex. We conclude with a short description of potential novel intraoperative optical techniques.

  11. The temporal structure of resting-state brain activity in the medial prefrontal cortex predicts self-consciousness.

    Science.gov (United States)

    Huang, Zirui; Obara, Natsuho; Davis, Henry Hap; Pokorny, Johanna; Northoff, Georg

    2016-02-01

    Recent studies have demonstrated an overlap between the neural substrate of resting-state activity and self-related processing in the cortical midline structures (CMS). However, the neural and psychological mechanisms mediating this so-called "rest-self overlap" remain unclear. To investigate the neural mechanisms, we estimated the temporal structure of spontaneous/resting-state activity, e.g. its long-range temporal correlations or self-affinity across time as indexed by the power-law exponent (PLE). The PLE was obtained in resting-state activity in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in 47 healthy subjects by functional magnetic resonance imaging (fMRI). We performed correlation analyses of the PLE and Revised Self-Consciousness Scale (SCSR) scores, which enabled us to access different dimensions of self-consciousness and specified rest-self overlap in a psychological regard. The PLE in the MPFC's resting-state activity correlated with private self-consciousness scores from the SCSR. Conversely, we found no correlation between the PLE and the other subscales of the SCSR (public, social) or between other resting-state measures, including functional connectivity, and the SCSR subscales. This is the first evidence for the association between the scale-free dynamics of resting-state activity in the CMS and the private dimension of self-consciousness. This finding implies the relationship of especially the private dimension of self with the temporal structure of resting-state activity.

  12. Inhibition of aminoacylase 3 protects rat brain cortex neuronal cells from the toxicity of 4-hydroxy-2-nonenal mercapturate and 4-hydroxy-2-nonenal

    Energy Technology Data Exchange (ETDEWEB)

    Tsirulnikov, Kirill; Abuladze, Natalia [Department of Medicine, University of California at Los Angeles, CA 90095 (United States); Bragin, Anatol [Department of Neurology, University of California at Los Angeles, CA 90095 (United States); Brain Research Institute, University of California at Los Angeles, CA 90095 (United States); Faull, Kym [Brain Research Institute, University of California at Los Angeles, CA 90095 (United States); Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, CA 90095 (United States); Pasarow Mass Spectrometry Laboratory, University of California at Los Angeles, CA 90095 (United States); Cascio, Duilio [Institute of Genomics and Proteomics, University of California at Los Angeles, CA 90095 (United States); Damoiseaux, Robert; Schibler, Matthew J. [California NanoSystems Institute, University of California at Los Angeles, CA 90095 (United States); Pushkin, Alexander, E-mail: apushkin@mednet.ucla.edu [Department of Medicine, University of California at Los Angeles, CA 90095 (United States)

    2012-09-15

    4-Hydroxy-2-nonenal (4HNE) and acrolein (ACR) are highly reactive neurotoxic products of lipid peroxidation that are implicated in the pathogenesis and progression of Alzheimer's and Parkinson's diseases. Conjugation with glutathione (GSH) initiates the 4HNE and ACR detoxification pathway, which generates the mercapturates of 4HNE and ACR that can be excreted. Prior work has shown that the efficiency of the GSH-dependent renal detoxification of haloalkene derived mercapturates is significantly decreased upon their deacetylation because of rapid transformation of the deacetylated products into toxic compounds mediated by β-lyase. The enzymes of the GSH-conjugation pathway and β-lyases are expressed in the brain, and we hypothesized that a similar toxicity mechanism may be initiated in the brain by the deacetylation of 4HNE- and ACR-mercapturate. The present study was performed to identify an enzyme(s) involved in 4HNE- and ACR-mercapturate deacetylation, characterize the brain expression of this enzyme and determine whether its inhibition decreases 4HNE and 4HNE-mercapturate neurotoxicity. We demonstrated that of two candidate deacetylases, aminoacylases 1 (AA1) and 3 (AA3), only AA3 efficiently deacetylates both 4HNE- and ACR-mercapturate. AA3 was further localized to neurons and blood vessels. Using a small molecule screen we generated high-affinity AA3 inhibitors. Two of them completely protected rat brain cortex neurons expressing AA3 from the toxicity of 4HNE-mercapturate. 4HNE-cysteine (4HNE-Cys) was also neurotoxic and its toxicity was mostly prevented by a β-lyase inhibitor, aminooxyacetate. The results suggest that the AA3 mediated deacetylation of 4HNE-mercapturate may be involved in the neurotoxicity of 4HNE.

  13. Gene expression profiling in postmortem prefrontal cortex of major depressive disorder.

    Science.gov (United States)

    Kang, Hyo Jung; Adams, David H; Simen, Arthur; Simen, Birgitte B; Rajkowska, Grazyna; Stockmeier, Craig A; Overholser, James C; Meltzer, Herbert Y; Jurjus, George J; Konick, Lisa C; Newton, Samuel S; Duman, Ronald S

    2007-11-28

    Investigations of the molecular mechanisms underlying major depressive disorder (MDD) have been hampered by the complexity of brain tissue and sensitivity of gene expression profiling approaches. To address these issues, we used discrete microdissections of postmortem dorsolateral prefrontal cortex (DLPFC) (area 9) and an oligonucleotide (60mer) microarray hybridization procedure that increases sensitivity without RNA amplification. Mixed-effects statistical methods were used to rigorously control for medication usage in the subset of medicated depressed subjects. These analyses yielded a rich profile of dysregulated genes. Two of the most highly dysregulated genes of interest were stresscopin, a neuropeptide involved in stress responses, and Forkhead box D3 (FOXD3), a transcription factor. Secondary cell-based analysis demonstrated that stresscopin and FoxD3 are increased in neurons of DLPFC gray matter of MDD subjects. These findings identify abnormal gene expression in a discrete region of MDD subjects and contribute to further elucidation of the molecular alterations of this complex mood disorder.

  14. Association between the fMRI manifestations of activated brain areas and muscle strength in patients with space-occupying lesions in motor cortex

    Institute of Scientific and Technical Information of China (English)

    Wenbin Zheng; Xiaoke Chen; Guorui Liu; Renhua Wu

    2006-01-01

    simple active finger-tapping movements, and for the 3 cases whose clinical symptoms were severe in the patient group, the simple passive finger-tapping movements were used. The manifestations in the activated brain areas were analyzed in the patients with brain tumor of different muscle strength and the controls. The motor deficit and activation of contralateral primary motor cortex (M1) in simple finger-tapping movements were observed in the patient group.MAIN OUTCOME MEASURES: ① Brain areas activated by finger-tapping movements in each group; ② Activated volumes in hemisphere by finger-tapping movements between groups.RESULTS: The contralateral M1 area could not be activated in 1 case in the patient group,, all the other 22 patients and 9 healthy subjects were involved in the analysis of results. ① In the control group, unilateral finger tapping movement activated the contralateral primary motor cortex (M1), bilateral SMA and bilateral PMC. The activation volume was the largest in contralateral primary motor cortex (M1), smaller in the SMA,and the smallest in PMC. The finger tapping movement in healthy subjects could activate contralateral primary motor cortex (M1), bilateral SMA and bilateral PMC, which had no obvious differences from the manifestations of brain functional area activated by active finger tapping. There was no significant difference in the volume of activated functional areas between right and left hands. In the patient group, the central sulcus around the tumor in the activated M1 area displaced towards dorsal or ventral side, also extended. The distance of displacement in the functional area was determined as compared with the contralateral central sulcus, and the results suggested the M1 displacement, including that there were 10 cases with the M1 displacement larger than 10 mm in the patients with motor deficit, which were obviously more than in those without motor deficit (n =1, P < 0.01), and the activated volume in contralateral M1 area

  15. [Structural organization of the fronto-parietal area of the sensory-motor cortex of the rat brain].

    Science.gov (United States)

    Kakabadze, I M; Kostenko, N A

    1990-01-01

    Organizational peculiarities of the frontal-parietal area of the sensomotor cortex are: parvicellularity, alveolar-like distribution of neurons, radial striation of the lower zone, distinctly manifested stratification of the higher zone in the cortical plate, the middle zones contain short axonal pyramidal, stellate and granular neurons. Formation of somato-somatic contacts is specific for interneuronal interaction. Peculiarity of the normal ultrastructure of the neuronal cytoplasm is presence of 2-4 subsuperficial cisterns in the section. In neuropil, which is presented mainly as axo-spinal assymetrical contacts of the I type after Grey, transversal profiles of tightly arranged and collected in fasciculi finest axonal collaterals and terminal dendritic ramifications are revealed.

  16. Effect of the Nicotinic α4β2-receptor Partial Agonist Varenicline on Non-invasive Brain Stimulation-Induced Neuroplasticity in the Human Motor Cortex.

    Science.gov (United States)

    Batsikadze, Giorgi; Paulus, Walter; Grundey, Jessica; Kuo, Min-Fang; Nitsche, Michael A

    2015-09-01

    Nicotine alters cognitive functions in animals and humans most likely by modification of brain plasticity. In the human brain, it alters plasticity induced by transcranial direct current stimulation (tDCS) and paired associative stimulation (PAS), probably by interference with calcium-dependent modulation of the glutamatergic system. We aimed to test this hypothesis further by exploring the impact of the α4β2-nicotinic receptor partial agonist varenicline on focal and non-focal plasticity, induced by PAS and tDCS, respectively. We administered low (0.1 mg), medium (0.3 mg), and high (1.0 mg) single doses of varenicline or placebo medication before PAS or tDCS on the left motor cortex of 25 healthy non-smokers. Corticospinal excitability was monitored by single-pulse transcranial magnetic stimulation-induced motor evoked potential amplitudes up to 36 h after plasticity induction. Whereas low-dose varenicline had no impact on stimulation-induced neuroplasticity, medium-dose abolished tDCS-induced facilitatory after-effects, favoring focal excitatory plasticity. High-dose application preserved cathodal tDCS-induced excitability diminution and focal excitatory PAS-induced facilitatory plasticity. These results are comparable to the impact of nicotine receptor activation and might help to further explain the involvement of specific receptor subtypes in the nicotinic impact on neuroplasticity and cognitive functions in healthy subjects and patients with neuropsychiatric diseases.

  17. Proteins in human brain cortex are modified by oxidation, glycoxidation, and lipoxidation. Effects of Alzheimer disease and identification of lipoxidation targets.

    Science.gov (United States)

    Pamplona, Reinald; Dalfó, Esther; Ayala, Victòria; Bellmunt, Maria Josep; Prat, Joan; Ferrer, Isidre; Portero-Otín, Manuel

    2005-06-03

    Diverse oxidative pathways, such as direct oxidation of amino acids, glycoxidation, and lipoxidation could contribute to Alzheimer disease pathogenesis. A global survey for the amount of structurally characterized probes for these reactions is lacking and could overcome the lack of specificity derived from measurement of 2,4-dinitrophenylhydrazine reactive carbonyls. Consequently we analyzed (i) the presence and concentrations of glutamic and aminoadipic semialdehydes, N(epsilon)-(carboxymethyl)-lysine, N(epsilon)-(carboxyethyl)-lysine, and N(epsilon)-(malondialdehyde)-lysine by means of gas chromatography/mass spectrometry, (ii) the biological response through expression of the receptor for advanced glycation end products, (iii) the fatty acid composition in brain samples from Alzheimer disease patients and age-matched controls, and (iv) the targets of N(epsilon)-(malondialdehyde)-lysine formation in brain cortex by proteomic techniques. Alzheimer disease was associated with significant, although heterogeneous, increases in the concentrations of all evaluated markers. Alzheimer disease samples presented increases in expression of the receptor for advanced glycation end products with high molecular heterogeneity. Samples from Alzheimer disease patients also showed content of docosahexaenoic acid, which increased lipid peroxidizability. In accordance, N(epsilon)-(malondialdehyde)-lysine formation targeted important proteins for both glial and neuronal homeostasis such as neurofilament L, alpha-tubulin, glial fibrillary acidic protein, ubiquinol-cytochrome c reductase complex protein I, and the beta chain of ATP synthase. These data support an important role for lipid peroxidation-derived protein modifications in Alzheimer disease pathogenesis.

  18. [Correlations of activity of neurons of sensorimotor cortex of the right and left brain hemispheres of rabbits during defensive dominant and "animal hypnosis"].

    Science.gov (United States)

    Bogdanov, A V; Galashina, A G; Karamysheva, N N

    2009-01-01

    A hidden excitation focus of the rhythmic nature (a rhythmic defensive dominant focus) was produced in the rabbit's CNS. The focus was formed by means of threshold electrodermal stimulation of the left forelimb by series of pulses consisting of 15-20 stimuli with 2 s intervals between the pulses. Correlated activity of cells in the sensorimotor cortex of the right and left brain hemispheres was analyzed. In cases when crosscorrelation histograms were constructed by the results of the analysis of discharges of the left-side cortical of neurons regarding high- and middle-amplitude pulses in a right hemisphere, 15 and 23 % of correlated neural pairs, respectively, revealed the prevalence of the rhythm identical or close to the initial rhythm of stimulation that formed the hidden excitation focus. In contrast, in cases when the same analysis was applied to the right-side cortical neurons regarding high- and middle-amplitude discharges in the left hemisphere, prevalence of the dominant 2-second rhythm was revealed in correlated activity of only 3 and 10% of neural pairs, respectively. After the exposure to "animal hypnosis" procedure, the distinctions between the brain in this parameter were eliminated.

  19. Area-specific effects of brain-derived neurotrophic factor (BDNF) genetic ablation on various neuronal subtypes of the mouse brain.

    Science.gov (United States)

    Grosse, Gisela; Djalali, Susann; Deng, Dong Rui; Höltje, Markus; Hinz, Britta; Schwartzkopff, Katharina; Cygon, Marcel; Rothe, Thomas; Stroh, Thomas; Hellweg, Rainer; Ahnert-Hilger, Gudrun; Hörtnag, Heide

    2005-05-12

    The effects of brain-derived neurotrophic factor (BDNF) on the development of presynaptic terminals and of neuronal subtypes in various brain areas were studied in BDNF-knockout (BDNF-/-) mice at postnatal days 15-17. Western analysis revealed no changes in the overall amount of a variety of synaptic proteins in BDNF-/- mice as compared to wild type mice. In addition, the complex between the vesicular proteins, synaptophysin and synaptobrevin, as well as their respective homodimers were unaltered. Moreover, no changes in the density of neurons were found in, e.g., the CA3 region of the hippocampus and the nucleus nervi facialis of BDNF-/- mice. However, cholinergic cells were reduced by 20% in the medial septum of BDNF-/- mice associated with a decrease in the activity of choline acetyltransferase and protein levels of nerve growth factor in the hippocampus by 16% and 44%, respectively. In the striatum, however, the total number of cholinergic cells were comparable in both groups, although the activity of choline acetyltransferase was decreased by 46%. In GABAergic interneurons, the expression of neuropeptides in various brain areas was differentially affected by BDNF deletion as revealed by immunohistochemistry. In the hippocampus and cortex of BDNF-/- mice, the density of neuropeptide Y-, somatostatin-, and parvalbumin-immunoreactive cells was drastically reduced, whereas the density of calretinin-positive cells was increased. The extent of these changes in neuropeptide-containing cells varied among hippocampal subregions. In the striatum, only the density of parvalbumin-immunoreactive cells was decreased by approximately 45%. In conclusion, BDNF deficiency is accompanied by a differential dysregulation in the expression of neuropeptides and calcium-binding proteins in otherwise intact GABAergic and glutamatergic neurons in a region-specific manner.

  20. Signaling by Drosophila capa neuropeptides.

    Science.gov (United States)

    Davies, Shireen-A; Cabrero, Pablo; Povsic, Manca; Johnston, Natalie R; Terhzaz, Selim; Dow, Julian A T

    2013-07-01

    The capa peptide family, originally identified in the tobacco hawk moth, Manduca sexta, is now known to be present in many insect families, with increasing publications on capa neuropeptides each year. The physiological actions of capa peptides vary depending on the insect species but capa peptides have key myomodulatory and osmoregulatory functions, depending on insect lifestyle, and life stage. Capa peptide signaling is thus critical for fluid homeostasis and survival, making study of this neuropeptide family attractive for novel routes for insect control. In Dipteran species, including the genetically tractable Drosophila melanogaster, capa peptide action is diuretic; via elevation of nitric oxide, cGMP and calcium in the principal cells of the Malpighian tubules. The identification of the capa receptor (capaR) in several insect species has shown this to be a canonical GPCR. In D. melanogaster, ligand-activated capaR activity occurs in a dose-dependent manner between 10(-6) and 10(-12)M. Lower concentrations of capa peptide do not activate capaR, either in adult or larval Malpighian tubules. Use of transgenic flies in which capaR is knocked-down in only Malpighian tubule principal cells demonstrates that capaR modulates tubule fluid secretion rates and in doing so, sets the organismal response to desiccation. Thus, capa regulates a desiccation-responsive pathway in D. melanogaster, linking its role in osmoregulation and fluid homeostasis to environmental response and survival. The conservation of capa action between some Dipteran species suggests that capa's role in desiccation tolerance may not be confined to D. melanogaster.

  1. Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury.

    Science.gov (United States)

    Guo, Zongjun; Wang, Lumin

    2012-07-25

    A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture (frequency 2-6 Hz, current intensity 2 mA) stimulation of the brachial plexus trunk on the healthy (right) side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy (right) side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.

  2. Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Zongjun Guo; Lumin Wang

    2012-01-01

    A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture (frequency 2-6 Hz, current intensity 2 mA) stimulation of the brachial plexus trunk on the healthy (right) side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy (right) side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.

  3. 4-Methylcatechol prevents derangements of brain-derived neurotrophic factor and TrkB-related signaling in anterior cingulate cortex in chronic pain with depression-like behavior.

    Science.gov (United States)

    Ishikawa, Kozo; Yasuda, Seiko; Fukuhara, Kayoko; Iwanaga, Yasutake; Ida, Yuika; Ishikawa, Junko; Yamagata, Hirotaka; Ono, Midori; Kakeda, Takahiro; Ishikawa, Toshizo

    2014-03-05

    Chronic pain with mood disorder, resulting from a peripheral nerve injury, is a serious clinical problem affecting the quality of life. A lack of brain-derived neurotrophic factor (BDNF) and abnormal intercellular signaling in the brain can mediate this symptom. BDNF is induced in cultured neurons by 4-methylcatechol (4-MC), but little is known about its role in pain-emotion. Thus, we characterized the actions of 4-MC on TrkB receptor-related pERK and BDNF mRNA in discreet brain regions related to pain-emotion after chronic pain in rat. Rats implanted with a stainless steel cannula into the lateral ventricular were subjected to chronic constriction injury (CCI). Pain was assessed by changes in paw withdrawal latency (PWL) to heat stimuli after CCI. Immobility time during the forced swimming testing was measured for depression-like behavior. Analgesic and antidepression modulations with 4-MC were examined by an anti-BDNF antibody (K252a, a TrkB receptor inhibitor). The animals were perfused and fixed (4% paraformaldehyde) for immunohistochemistry analysis (c-FOS/pERK). BDNF mRNA expression (anterior cingulate cortex) was determined using reverse transcription-PCR. Rats showed a sustained decrease in PWL, associated with a prolonged immobility time after CCI. 4-MC reduced decreases in PWL and increased immobility time. 4-MC reduced increases in pERK immunoreactivity and decreases in BDNF mRNA expression in regions related to pain and the limbic system. Anti-BDNF blocked effects induced by 4-MC. We suggest that a lack of BDNF associated with activated extracellular signal-regulated kinase in the pain-emotion network may be involved in depression-like behavior during chronic pain. 4-MC ameliorates pain-emotion symptoms by inducing BDNF and normalizing pERK activities.

  4. Effect of tricyclic antidepressants on transmitter-stimulated inositol phosphate production in rat brain cortex in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, S.; Enna, S.J.

    1986-03-01

    Tricyclic antidepressants (TCAs) have anticholinergic and ..cap alpha..-adrenergic blocking properties. The present study was undertaken to examine the effects of amitriptyline, imipramine, and desipramine on inositol phosphate accumulation, a brain second messenger system associated with cholinergic and adrenergic receptors. Whereas the TCAs were 28 to 400-fold weaker than atropine as inhibitors of /sup 3/H-QNB binding to brain cholinergic receptors, they were 600 to 2000-fold less active than atropine as inhibitors of carbachol-stimulated IP accumulation in brain. In contrast, the relative potencies of the TCAs and prazosin to inhibit norepinephrine-stimulated IP accumulation and /sup 3/H-prazosin binding appeared to be similar in the two assays. The results suggest pharmacological differences between the cholinergic receptors labeled in the ONB binding assay and those mediating the IP response, whereas the ..cap alpha../sub 1/-adrenergic receptors appear to be similar in the two systems. Since atropine is considered a nonselective muscarinic antagonist, it is possible that the TCAs may differentiate between cholinergic receptor subtypes, which may be an important component of their clinical response.

  5. 醒脑静对脑出血患者 S100B、神经肽 Y和脑水肿的影响%Impact of Xingnaojing on the S100B,neuropeptide Y and brain edema of patients with cerebral hemorrhage

    Institute of Scientific and Technical Information of China (English)

    刘颖

    2015-01-01

    Objective To investigate the impact of Xingnaojing on the S100B,neuropeptide Y and brain edema of patients with cerebral hemorrhage. Methods A total of 72 patients with cerebral hemorrhage were selected in the People's Hos-pital of Yichun in 2014,they were randomly divided into control group and observation group,36 cases in each group. Control group were given edaravone treatment,observation group were given Xingnaojing on the basis of control group. Before treatment and after treatment of 1,2 weeks S100B,neuropeptide Y levels,brain edema volume and incidence of adverse reactions be-tween the two groups were compared. Results There was interaction between time and method(P 0. 05),after treatment of 1 week,S100B levels,brain edema volume showed no significant differences between the two groups(P > 0. 05),after treatment of 1 week,neuropeptide Y levels of ob-servation group was lower than that of control group(P < 0. 05),after treatment of 2 week,S100B,neuropeptide Y levels of observation group were lower than those of control group,brain edema volume of observation group was less than that of control group(P < 0. 05);no one of the two groups occurred serious adverse reactions. Conclusion Xingnaojing can decrease S100B,neuropeptide Y levels of patients with cerebral hemorrhage,improve patients' brain edema.%目的:探讨醒脑静对脑出血患者 S100B、神经肽 Y 和脑水肿的影响。方法选取2014年宜春市人民医院收治的脑出血患者72例,随机分为对照组与观察组,各36例。对照组患者予以依达拉奉治疗,观察组患者在对照组基础上加用醒脑静治疗。观察两组患者治疗前及治疗1、2周 S100B、神经肽 Y 水平、脑水肿体积及不良反应发生情况。结果时间与方法有交互作用(P <0.05),组间比较,差异均有统计学意义( P <0.05),时间间比较,差异均有统计学意义(P <0.05),治疗前两组患者 S100B、神经肽 Y 水平、脑水肿体

  6. Rod microglia: elongation, alignment, and coupling to form trains across the somatosensory cortex after experimental diffuse brain injury

    Directory of Open Access Journals (Sweden)

    Ziebell Jenna M

    2012-10-01

    Full Text Available Abstract Background Since their discovery, the morphology of microglia has been interpreted to mirror their function, with ramified microglia constantly surveying the micro-environment and rapidly activating when changes occur. In 1899, Franz Nissl discovered what we now recognize as a distinct microglial activation state, microglial rod cells (Stäbchenzellen, which he observed adjacent to neurons. These rod-shaped microglia are typically found in human autopsy cases of paralysis of the insane, a disease of the pre-penicillin era, and best known today from HIV-1-infected brains. Microglial rod cells have been implicated in cortical ‘synaptic stripping’ but their exact role has remained unclear. This is due at least in part to a scarcity of experimental models. Now we have noted these rod microglia after experimental diffuse brain injury in brain regions that have an associated sensory sensitivity. Here, we describe the time course, location, and surrounding architecture associated with rod microglia following experimental diffuse traumatic brain injury (TBI. Methods Rats were subjected to a moderate midline fluid percussion injury (mFPI, which resulted in transient suppression of their righting reflex (6 to 10 min. Multiple immunohistochemistry protocols targeting microglia with Iba1 and other known microglia markers were undertaken to identify the morphological activation of microglia. Additionally, labeling with Iba1 and cell markers for neurons and astrocytes identified the architecture that surrounds these rod cells. Results We identified an abundance of Iba1-positive microglia with rod morphology in the primary sensory barrel fields (S1BF. Although present for at least 4 weeks post mFPI, they developed over the first week, peaking at 7 days post-injury. In the absence of contusion, Iba1-positive microglia appear to elongate with their processes extending from the apical and basal ends. These cells then abut one another and lay adjacent

  7. Mapping inter-regional connectivity of the entire cortex to characterize major depressive disorder: a whole-brain diffusion tensor imaging tractography study.

    Science.gov (United States)

    Korgaonkar, Mayuresh S; Cooper, Nicholas J; Williams, Leanne M; Grieve, Stuart M

    2012-06-20

    Diffusion tensor imaging (DTI) can be used to study the organization of brain white matter noninvasively. The aim of this study was to present a proof of concept for integrating DTI with high-resolution anatomical (T1) images to map and assess inter-regional connectivity across the entire cortex in a cohort of healthy participants and compared with patients with major depressive disorder. We used MRI data of 23 patients and 23 matched controls, assessed as part of baseline testing in the International Study to Predict Optimized Treatment in Depression (iSPOT-D). Freesurfer was used to analyze the T1 images to automatically label 35 gyral-based areas for each hemisphere. DTI tractography was performed to parcellate intercortical tracts using each of these areas in seed-target combinations. We quantified fractional anisotropy, number-of-fiber connections, and fiber path length for each DTI connection, with the goal of identifying the best measure or combination of measures to characterize major depression. The best classification accuracy for the individual measures was achieved using the number-of-fibers data, whereas the combination model provided a slight improvement. The most discriminant features between the two groups were for white matter associated with the limbic, frontal, and thalamic projection fibers and as part of cortical connections between the left inferior temporal and the postcentral cortex; the left parstriangularis and the left superior frontal; the left cuneus and the corpus callosum; the left lingual and the right lateral occipital, the right superior parietal and the right superior temporal cortices; and the right inferior parietal and the right insula and postcentral cortices.

  8. N-methyl-D-aspartate (NMDA)-stimulated noradrenaline (NA) release in rat brain cortex is modulated by presynaptic H3-receptors.

    Science.gov (United States)

    Fink, K; Schlicker, E; Göthert, M

    1994-02-01

    In superfused rat brain cortex slices and synaptosomes preincubated with [3H]noradrenaline the effect of agonists or antagonists at presynaptic H3 receptors on NMDA-evoked [3H]noradrenaline release was investigated. In experiments on slices, histamine and the preferential H3 receptor agonist R-(-)-alpha-methylhistamine inhibited NMDA-evoked tritium overflow (IC20 values 0.27 mumol/l or 0.032 mumol/l, respectively); S-(+)-alpha-methylhistamine (up to 10 mumol/l) as well as the selective H1 receptor agonist (2-(2-thiazolyl)ethylamine and the selective H2 receptor agonist dimaprit (each up to 10 mumol/l) were ineffective. The H3 receptor antagonist thioperamide abolished the inhibitory effect of histamine whereas the preferential H1 receptor antagonist dimetindene and the preferential H2 receptor antagonist ranitidine were ineffective. In experiments on synaptosomes, histamine and R-(-)-alpha-methylhistamine inhibited NMDA-evoked tritium overflow, whereas 2-(2-thiazolyl)ethylamine or dimaprit had no effect. The inhibitory effect of histamine was abolished by thioperamide. When tritium overflow was stimulated by NMDA in the presence of omega-conotoxin GVIA (which by itself decreased the response to NMDA by about 55%), R-(-)-alpha-methylhistamine did not inhibit NMDA-evoked overflow. It is concluded that NMDA-evoked noradrenaline release in the cerebral cortex can be modulated by inhibitory H3 receptors. NMDA receptors and H3 receptors are both located presynaptically and may interact at the same noradrenergic varicosity. An unimpaired function of the N-type voltage-sensitive calcium channel probably is a prerequisite for the inhibition of NMDA-evoked noradrenaline release by H3 receptor stimulation.

  9. Neuropeptide Receptor Transcriptome Reveals Unidentified Neuroendocrine Pathways

    Science.gov (United States)

    Yamanaka, Naoki; Yamamoto, Sachie; Žitňan, Dušan; Watanabe, Ken; Kawada, Tsuyoshi; Satake, Honoo; Kaneko, Yu; Hiruma, Kiyoshi; Tanaka, Yoshiaki; Shinoda, Tetsuro; Kataoka, Hiroshi

    2008-01-01

    Neuropeptides are an important class of molecules involved in diverse aspects of metazoan development and homeostasis. Insects are ideal model systems to investigate neuropeptide functions, and the major focus of insect neuropeptide research in the last decade has been on the identification of their receptors. Despite these vigorous efforts, receptors for some key neuropeptides in insect development such as prothoracicotropic hormone, eclosion hormone and allatotropin (AT), remain undefined. In this paper, we report the comprehensive cloning of neuropeptide G protein-coupled receptors from the silkworm, Bombyx mori, and systematic analyses of their expression. Based on the expression patterns of orphan receptors, we identified the long-sought receptor for AT, which is thought to stimulate juvenile hormone biosynthesis in the corpora allata (CA). Surprisingly, however, the AT receptor was not highly expressed in the CA, but instead was predominantly transcribed in the corpora cardiaca (CC), an organ adjacent to the CA. Indeed, by using a reverse-physiological approach, we purified and characterized novel allatoregulatory peptides produced in AT receptor-expressing CC cells, which may indirectly mediate AT activity on the CA. All of the above findings confirm the effectiveness of a systematic analysis of the receptor transcriptome, not only in characterizing orphan receptors, but also in identifying novel players and hidden mechanisms in important biological processes. This work illustrates how using a combinatorial approach employing bioinformatic, molecular, biochemical and physiological methods can help solve recalcitrant problems in neuropeptide research. PMID:18725956

  10. Neuropeptide receptor transcriptome reveals unidentified neuroendocrine pathways.

    Directory of Open Access Journals (Sweden)

    Naoki Yamanaka

    Full Text Available Neuropeptides are an important class of molecules involved in diverse aspects of metazoan development and homeostasis. Insects are ideal model systems to investigate neuropeptide functions, and the major focus of insect neuropeptide research in the last decade has been on the identification of their receptors. Despite these vigorous efforts, receptors for some key neuropeptides in insect development such as prothoracicotropic hormone, eclosion hormone and allatotropin (AT, remain undefined. In this paper, we report the comprehensive cloning of neuropeptide G protein-coupled receptors from the silkworm, Bombyx mori, and systematic analyses of their expression. Based on the expression patterns of orphan receptors, we identified the long-sought receptor for AT, which is thought to stimulate juvenile hormone biosynthesis in the corpora allata (CA. Surprisingly, however, the AT receptor was not highly expressed in the CA, but instead was predominantly transcribed in the corpora cardiaca (CC, an organ adjacent to the CA. Indeed, by using a reverse-physiological approach, we purified and characterized novel allatoregulatory peptides produced in AT receptor-expressing CC cells, which may indirectly mediate AT activity on the CA. All of the above findings confirm the effectiveness of a systematic analysis of the receptor transcriptome, not only in characterizing orphan receptors, but also in identifying novel players and hidden mechanisms in important biological processes. This work illustrates how using a combinatorial approach employing bioinformatic, molecular, biochemical and physiological methods can help solve recalcitrant problems in neuropeptide research.

  11. Mapping Prefrontal Cortex Functions in Human Infancy

    Science.gov (United States)

    Grossmann, Tobias

    2013-01-01

    It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much…

  12. Neuropeptide y promotes neurogenesis in murine subventricular zone

    DEFF Research Database (Denmark)

    Agasse, Fabienne; Bernardino, Liliana; Christiansen, Søren H

    2008-01-01

    Stem cells of the subventricular zone (SVZ) represent a reliable source of neurons for cell replacement. Neuropeptide Y (NPY) promotes neurogenesis in the hippocampal subgranular layer and the olfactory epithelium and may be useful for the stimulation of SVZ dynamic in brain repair purposes. We...... describe that NPY promotes SVZ neurogenesis. NPY (1 microM) treatments increased proliferation at 48 hours and neuronal differentiation at 7 days in SVZ cell cultures. NPY proneurogenic properties are mediated via the Y1 receptor. Accordingly, Y1 receptor is a major active NPY receptor in the mouse SVZ......-Jun-NH(2)-terminal kinase signal in growing axons, consistent with axonogenesis. NPY, as a promoter of SVZ neurogenesis, is a crucial factor for future development of cell-based brain therapy. Disclosure of potential conflicts of interest is found at the end of this article....

  13. Rapid and slow nitric oxide responses during conducted vasodilation in the in vivo intestine and brain cortex microvasculatures.

    Science.gov (United States)

    Bohlen, H Glenn

    2011-11-01

    Conduction of arteriolar vasodilation is initiated by activation of nitric oxide (NO) mechanisms, but dependent on conduction of hyperpolarization. Most studies have used brief (vasodilation to evaluate the fast conduction processes. However, most arteriolar mechanisms involving NO production persist for minutes. In this study, fast and slower components of arteriolar conduction in the in vivo rat brain and small intestine were compared using three-minute stimulation of NO-dependent vasodilation and measurement of [NO] at the distal sites. Within 10-15 seconds, both vasculatures had a rapidly conducted vasodilation and dilation at distance had a fast but small [NO] component. A slower but larger distal vasodilation occurred after 60-90 seconds in the intestine, but not the brain, and was associated with a substantial increase in [NO]. This slowly developed dilation appeared to be caused by flow mediated responses of larger arterioles as smaller arterioles dilated to lower downstream resistance. These results indicate while the intestinal and cerebral arterioles have a fast conducted vasodilation system, the intestinal arterioles also have a slower but larger dilation of major arterioles that is NO related and dependent on the conduction of vasodilation between small arterioles.

  14. Synchronization between the anterior and posterior cortex determines consciousness level in patients with traumatic brain injury (TBI).

    Science.gov (United States)

    Leon-Carrion, Jose; Leon-Dominguez, Umberto; Pollonini, Luca; Wu, Meng-Hung; Frye, Richard E; Dominguez-Morales, Maria Rosario; Zouridakis, George

    2012-10-02

    Survivors of traumatic brain injury (TBI) often suffer disorders of consciousness as a result of a breakdown in cortical connectivity. However, little is known about the neural discharges and cortical areas working in synchrony to generate consciousness in these patients. In this study, we analyzed cortical connectivity in patients with severe neurocognitive disorder (SND) and in the minimally conscious state (MCS). We found two synchronized networks subserving consciousness; one retrolandic (cognitive network) and the other frontal (executive control network). The synchrony between these networks is severely disrupted in patients in the MCS as compared to those with better levels of consciousness and a preserved state of alertness (SND). The executive control network could facilitate the synchronization and coherence of large populations of distant cortical neurons using high frequency oscillations on a precise temporal scale. Consciousness is altered or disappears after losing synchrony and coherence. We suggest that the synchrony between anterior and retrolandic regions is essential to awareness, and that a functioning frontal lobe is a surrogate marker for preserved consciousness. This article is part of a Special Issue entitled: Brain Integration. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex

    Science.gov (United States)

    Gan, Gabriela; Guevara, Alvaro; Marxen, Michael; Neumann, Maike; Jünger, Elisabeth; Kobiella, Andrea; Mennigen, Eva; Pilhatsch, Maximilian; Schwarz, Daniel; Zimmermann, Ulrich S.; Smolka, Michael N.

    2014-01-01

    Background A self-enhancing loop between impaired inhibitory control under alcohol and alcohol consumption has been proposed as a possible mechanism underlying dysfunctional drinking in susceptible people. However, the neural underpinnings of alcohol-induced impairment of inhibitory control are widely unknown. Methods We measured inhibitory control in fifty young adults with a stop-signal task (SST) during functional magnetic resonance imaging (fMRI). In a single-blind placebo-controlled cross-over design, all participants performed the SST once under alcohol with a breath alcohol concentration (BrAC) of 0.6 g/kg, and once under placebo. In addition, alcohol consumption was assessed using a free-access alcohol self-administration (ASA) paradigm in the same participants. Results Inhibitory control was robustly decreased under alcohol compared to placebo indicated by longer stop-signal reaction times (SSRTs). On the neural level, impaired inhibitory control under alcohol was associated with attenuated brain responses in the right fronto-temporal portion of the inhibition network that supports the attentional capture of infrequent stop-signals, and subsequent updating of action plans from response execution to inhibition. Furthermore, the extent of alcohol-induced impairment of inhibitory control predicted free-access alcohol consumption. Conclusion We suggest that during inhibitory control alcohol affects cognitive processes preceding actual motor inhibition. Under alcohol, decreased brain responses in right fronto-temporal areas might slow down the attentional capture of infrequent stop-signals and subsequent updating of action plans which leads to impaired inhibitory control. In turn, pronounced alcohol-induced impairment of inhibitory control may enhance alcohol consumption in young adults which might promote future alcohol problems. PMID:24560581

  16. Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex.

    Science.gov (United States)

    Gan, Gabriela; Guevara, Alvaro; Marxen, Michael; Neumann, Maike; Jünger, Elisabeth; Kobiella, Andrea; Mennigen, Eva; Pilhatsch, Maximilian; Schwarz, Daniel; Zimmermann, Ulrich S; Smolka, Michael N

    2014-11-01

    A self-enhancing loop between impaired inhibitory control under alcohol and alcohol consumption has been proposed as a possible mechanism underlying dysfunctional drinking in susceptible people. However, the neural underpinnings of alcohol-induced impairment of inhibitory control are widely unknown. We measured inhibitory control in 50 young adults with a stop-signal task during functional magnetic resonance imaging. In a single-blind placebo-controlled cross-over design, all participants performed the stop-signal task once under alcohol with a breath alcohol concentration of .6 g/kg and once under placebo. In addition, alcohol consumption was assessed with a free-access alcohol self-administration paradigm in the same participants. Inhibitory control was robustly decreased under alcohol compared with placebo, indicated by longer stop-signal reaction times. On the neural level, impaired inhibitory control under alcohol was associated with attenuated brain responses in the right fronto-temporal portion of the inhibition network that supports the attentional capture of infrequent stop-signals and subsequent updating of action plans from response execution to inhibition. Furthermore, the extent of alcohol-induced impairment of inhibitory control predicted free-access alcohol consumption. We suggest that during inhibitory control alcohol affects cognitive processes preceding actual motor inhibition. Under alcohol, decreased brain responses in right fronto-temporal areas might slow down the attentional capture of infrequent stop-signals and subsequent updating of action plans, which leads to impaired inhibitory control. In turn, pronounced alcohol-induced impairment of inhibitory control might enhance alcohol consumption in young adults, which might promote future alcohol problems. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. The neuroplastic index p-FADD/FADD and phosphoprotein PEA-15, interacting at GABAA receptor, are upregulated in brain cortex during midazolam-induced hypnosis in mice.

    Science.gov (United States)

    Álvaro-Bartolomé, María; García-Sevilla, Jesús A

    2015-11-01

    Fas-associated death domain (FADD) adaptor is involved in the signaling of metabotropic G protein-coupled receptors, whose agonists stimulate its phosphoryaltion (p) increasing p-FADD/FADD ratio in brain. Whether FADD might also participate in the activation of dissimilar receptors such as the ligand-gated ion channels is not known. This study investigated the role of FADD and phosphoprotein-enriched in astrocytes of 15 kDa (PEA-15, a FADD partner) in the activation of γ-aminobutyric acid-A (GABAA) receptor, which mediates the hypnotic effect of midazolam. The main findings revealed that during the time course of midazolam (60 mg/kg)-induced hypnosis in mice (about 2 h) p-FADD (and p-FADD/FADD ratio) as well as p-PEA (and its phosphorylating Akt1 kinase) were markedly increased (36-80%) in brain cortex, and these effects were partially (only p-FADD) or fully prevented by flumazenil (a neutral allosteric ligand) and FG 7142 (a partial negative allosteric ligand) acting at GABAA receptors. The upregulation of cortical p-FADD/FADD was exclusively observed in the nucleus (up to 2.8-fold), where the transciption factor NF-κB was also increased (up to 46%), and that of p-PEA/p-Akt1 only in the cytosol (up to 53%), suggesting that p-FADD/p-PEA/p-Akt1 are involved in sleep-induced neuroplasticity. Repeated treatment with midazolam (60 mg/kg, 4 days) induced behavioral (prolonged sleep latency and reduced sleeping time) and neurochemical (reduced p-FADD/p-PEA contents) tolerance. These findings indicated that p-FADD/p-PEA are novel molecules in GABAA receptor signaling and that cortical p-PEA and p-FADD, working in tandem, are involved in the complex molecular processes leading to the hypnotic effect of midazolam in mice.

  18. Motor cortex electrical stimulation promotes axon outgrowth to brain stem and spinal targets that control the forelimb impaired by unilateral corticospinal injury.

    Science.gov (United States)

    Carmel, Jason B; Kimura, Hiroki; Berrol, Lauren J; Martin, John H

    2013-04-01

    We previously showed that electrical stimulation of motor cortex (M1) after unilateral pyramidotomy in the rat increased corticospinal tract (CST) axon length, strengthened spinal connections, and restored forelimb function. Here, we tested: (i) if M1 stimulation only increases spinal axon length or if it also promotes connections to brain stem forelimb control centers, especially magnocellular red nucleus; and (ii) if stimulation-induced increase in axon length depends on whether pyramidotomy denervated the structure. After unilateral pyramidotomy, we electrically stimulated the forelimb area of intact M1, to activate the intact CST and other corticofugal pathways, for 10 days. We anterogradely labeled stimulated M1 and measured axon length using stereology. Stimulation increased axon length in both the spinal cord and magnocellular red nucleus, even though the spinal cord is denervated by pyramidotomy and the red nucleus is not. Stimulation also promoted outgrowth in the cuneate and parvocellular red nuclei. In the spinal cord, electrical stimulation caused increased axon length ipsilateral, but not contralateral, to stimulation. Thus, stimulation promoted outgrowth preferentially to the sparsely corticospinal-innervated and impaired side. Outgrowth resulted in greater axon density in the ipsilateral dorsal horn and intermediate zone, resembling the contralateral termination pattern. Importantly, as in spinal cord, increase in axon length in brain stem also was preferentially directed towards areas less densely innervated by the stimulated system. Thus, M1 electrical stimulation promotes increases in corticofugal axon length to multiple M1 targets. We propose the axon length change was driven by competition into an adaptive pattern resembling lost connections. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  19. Effects of ketamine administration on mTOR and reticulum stress signaling pathways in the brain after the infusion of rapamycin into prefrontal cortex.

    Science.gov (United States)

    Abelaira, Helena M; Réus, Gislaine Z; Ignácio, Zuleide M; Dos Santos, Maria Augusta B; de Moura, Airam B; Matos, Danyela; Demo, Júlia P; da Silva, Júlia B I; Michels, Monique; Abatti, Mariane; Sonai, Beatriz; Dal Pizzol, Felipe; Carvalho, André F; Quevedo, João

    2017-04-01

    Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC. Male adult Wistar rats received pharmacological mTOR inhibitor, rapamycin (0.2 nmol), or vehicle into the PFC and then a single dose of ketamine (15 mg/kg, i.p.). The immunocontent of mTOR, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), eukaryotic elongation factor 2 kinase (eEF2K) homologous protein (CHOP), PKR-like ER kinase (PERK) and inositol-requiring enzyme 1 (IRE1) - alpha were determined in the brain. The mTOR levels were reduced in the rapamycin group treated with saline and ketamine in the PFC; p4EBP1 levels were reduced in the rapamycin group treated with ketamine in the PFC and nucleus accumbens; the levels of peEF2K were increased in the PFC in the vehicle group treated with ketamine and reduced in the rapamycin group treated with ketamine. The PERK and IRE1-alpha levels were decreased in the PFC in the rapamycin group treated with ketamine. Our results suggest that mTOR signaling inhibition by rapamycin could be involved, at least in part, with the mechanism of action of ketamine; and the ketamine antidepressant on ER stress pathway could be also mediated by mTOR signaling pathway in certain brain structures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Interactions of Circadian Rhythmicity, Stress and Orexigenic Neuropeptide Systems: Implications for Food Intake Control

    Science.gov (United States)

    Blasiak, Anna; Gundlach, Andrew L.; Hess, Grzegorz; Lewandowski, Marian H.

    2017-01-01

    Many physiological processes fluctuate throughout the day/night and daily fluctuations are observed in brain and peripheral levels of several hormones, neuropeptides and transmitters. In turn, mediators under the “control” of the “master biological clock” reciprocally influence its function. Dysregulation in the rhythmicity of hormone release as well as hormone receptor sensitivity and availability in different tissues, is a common risk-factor for multiple clinical conditions, including psychiatric and metabolic disorders. At the same time circadian rhythms remain in a strong, reciprocal interaction with the hypothalamic-pituitary-adrenal (HPA) axis. Recent findings point to a role of circadian disturbances and excessive stress in the development of obesity and related food consumption and metabolism abnormalities, which constitute a major health problem worldwide. Appetite, food intake and energy balance are under the influence of several brain neuropeptides, including the orexigenic agouti-related peptide, neuropeptide Y, orexin, melanin-concentrating hormone and relaxin-3. Importantly, orexigenic neuropeptide neurons remain under the control of the circadian timing system and are highly sensitive to various stressors, therefore the potential neuronal mechanisms through which disturbances in the daily rhythmicity and stress-related mediator levels contribute to food intake abnormalities rely on reciprocal interactions between these elements. PMID:28373831

  1. Motor cortex stimulation(MCS) for intractable complex regional pain syndrome (CRPS) type II: PSM analysis of Tc-99m ECD brain perfusion SPECT

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    Chung, Y. A.; Son, B. C.; Yoo, I. R.; Kim, S. H.; Kim, E. N.; Park, Y. H.; Lee, S. Y.; Sohn, H. S.; Chung, S. K. [College of Medicine, The Catholic Univ. of Korea, Seoul (Korea, Republic of)

    2001-07-01

    We had experienced a patient with intractable CRPS in whom statistical parametric mapping (SPM) analysis of cerebral perfusion explained the mechanism of pain control by MCS. A 43-year-old man presented spontaneous severe burning pain in his left hand and forearm and allodynia over the left arm and left hemibody. After the electrodes for neuromodulation therapy were inserted in the central sulcus, the baseline and stimulation brain perfusion SPECT using Tc-99m ECD were obtained within two days. The differences between the baseline and stimulation SPECT images, estimated at every voxel using t-statistics using SPM-99 software, were considered significant at a threshold of uncorrected P values less than 0.01. Among several areas significantly activated following pain relief with MCS, ipsilateral pyramidal tract in the cerebral peduncle might be related to the mechanism of pain control with MCS through efferent motor pathway. The result suggested that corticospinal neurons themselves or motor cortex efferent pathway maintained by the presence of intact corticospinal neurons could play an important role in producing pain control after MCS. This study would helpful in understanding of neurophysiology.

  2. Frontopolar cortex and decision-making efficiency: comparing brain activity of experts with different professional background during an exploration-exploitation task

    Directory of Open Access Journals (Sweden)

    Daniella eLaureiro-Martínez

    2014-01-01

    Full Text Available An optimal balance between efficient exploitation of available resources and creative exploration of alternatives is critical for adaptation and survival. Previous studies associated these behavioral drives with, respectively, the dopaminergic mesocorticolimbic system and frontopolar-intraparietal networks. We study the activation of these systems in two age and gender-matched groups of experienced decision-makers differing in prior professional background, with the aim to understand the neural bases of individual differences in decision-making efficiency (performance divided by response time. We compare brain activity of entrepreneurs (who currently manage the organization they founded based on their venture idea and managers (who are constantly involved in making strategic decisions but have no venture experience engaged in a gambling-task assessing exploitative vs. explorative decision-making. Compared with managers, entrepreneurs showed higher decision-making efficiency, and a stronger activation in regions of frontopolar cortex previously associated with explorative choice. Moreover, activity across a network of regions previously linked to explore/exploit tradeoffs explained individual differences in choice efficiency. These results suggest new avenues for the study of individual differences in the neural antecedents of efficient decision-making.

  3. Use of functional near-infrared spectroscopy to evaluate the effects of anodal transcranial direct current stimulation on brain connectivity in motor-related cortex

    Science.gov (United States)

    Yan, Jiaqing; Wei, Yun; Wang, Yinghua; Xu, Gang; Li, Zheng; Li, Xiaoli

    2015-04-01

    Transcranial direct current stimulation (tDCS) is a noninvasive, safe and convenient neuro-modulatory technique in neurological rehabilitation, treatment, and other aspects of brain disorders. However, evaluating the effects of tDCS is still difficult. We aimed to evaluate the effects of tDCS using hemodynamic changes using functional near-infrared spectroscopy (fNIRS). Five healthy participants were employed and anodal tDCS was applied to the left motor-related cortex, with cathodes positioned on the right dorsolateral supraorbital area. fNIRS data were collected from the right motor-related area at the same time. Functional connectivity (FC) between intracortical regions was calculated between fNIRS channels using a minimum variance distortion-less response magnitude squared coherence (MVDR-MSC) method. The levels of Oxy-HbO change and the FC between channels during the prestimulation, stimulation, and poststimulation stages were compared. Results showed no significant level difference, but the FC measured by MVDR-MSC significantly decreased during tDCS compared with pre-tDCS and post-tDCS, although the FC difference between pre-tDCS and post-tDCS was not significant. We conclude that coherence calculated from resting state fNIRS may be a useful tool for evaluating the effects of anodal tDCS and optimizing parameters for tDCS application.

  4. The Role of Neonatal Carnitine Palmitoyl Transferase Deficiency Type II on Proliferation of Neuronal Progenitor Cells and Layering of the Cerebral Cortex in the Developing Brain

    Directory of Open Access Journals (Sweden)

    Heepeel Chang

    2007-06-01

    Full Text Available Neonatal Carnitine Palmitoyl Transferase Deficiency Type II, characterized by the absence of CPT II enzyme, is one of the lethal disorders of mitochondrial fatty acid oxidation. CPT II regulates the conversion of long chain fatty acids, so that its product, acyl-CoA esters, can enter the Krebs cycle and generate energy. Neonatal mutations of CPT II lead to severe disruption of the metabolism of long-chain fatty acids and result in dysmorphic features, cystic renal dysplasia, and neuronal migration defects. Examination of the brain from an approximately 15-week gestation human fetus with CPT II deficiency revealed premature formation of cerebral cortical gyri and sulci and significantly lower levels of neuronal cell proliferation in the ventricular and subventricular zones as compared to the reference cases. We used immunohistochemical markers to further characterize the effect of CPT II deficiency on progenitor cell proliferation and layering of neurons. These studies demonstrated a premature generation of layer 5 cortical neurons. In addition, both the total number and percentage of progenitor cells proliferating in the ventricular zone were markedly reduced in the CPT II case in comparison to a reference case. Our results indicate that CPT II deficiency alters the normal program of cellular proliferation and differentiation in the cortex, with early differentiation of progenitor cells associated with premature cortical maturation.

  5. Genetic Variation in the Catechol-O-Methyl Transferase Val108/158Met Is Linked to the Caudate and Posterior Cingulate Cortex Volume in Healthy Subjects: Voxel-Based Morphometry Analysis of Brain Magnetic Resonance Imaging.

    Directory of Open Access Journals (Sweden)

    Keita Watanabe

    Full Text Available The effect of the catechol-O-methyltransferase (COMT Val158Met polymorphism on brain morphology has been investigated but remains controversial. We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings. We investigated the brain morphology using 3-Tesla magnetic resonance imaging in 27 Val/Val and 22 Val/Met individuals. Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048]. This study demonstrates that interacting functional variants of COMT affect gray matter regional volumes in healthy subjects.

  6. Genetic Variation in the Catechol-O-Methyl Transferase Val108/158Met Is Linked to the Caudate and Posterior Cingulate Cortex Volume in Healthy Subjects: Voxel-Based Morphometry Analysis of Brain Magnetic Resonance Imaging

    Science.gov (United States)

    Watanabe, Keita; Kakeda, Shingo; Yoshimura, Reiji; Ide, Satoru; Hayashi, Kenji; Katsuki, Asuka; Umene-Nakano, Wakako; Watanabe, Rieko; Abe, Osamu; Korogi, Yukunori

    2015-01-01

    The effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain morphology has been investigated but remains controversial. We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings. We investigated the brain morphology using 3-Tesla magnetic resonance imaging in 27 Val/Val and 22 Val/Met individuals. Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR)-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048]. This study demonstrates that interacting functional variants of COMT affect gray matter regional volumes in healthy subjects. PMID:26566126

  7. Expression and distribution of neuropeptides in the nervous system of the crab Carcinus maenas and their roles in environmental stress.

    Science.gov (United States)

    Zhang, Yuzhuo; Buchberger, Amanda; Muthuvel, Gajanthan; Li, Lingjun

    2015-12-01

    Environmental fluctuations, such as salinity, impose serious challenges to marine animal survival. Neuropeptides, signaling molecules involved in the regulation process, and the dynamic changes of their full complement in the stress response have yet to be investigated. Here, a MALDI-MS-based stable isotope labeling quantitation strategy was used to investigate the relationship between neuropeptide expression and adaptability of Carcinus maenas to various salinity levels, including high (60 parts per thousand [p.p.t.]) and low (0 p.p.t.) salinity, in both the crustacean pericardial organ (PO) and brain. Moreover, a high salinity stress time course study was conducted. MS imaging (MSI) of neuropeptide localization in C. maenas PO was also performed. As a result of salinity stress, multiple neuropeptide families exhibited changes in their relative abundances, including RFamides (e.g. APQGNFLRFamide), RYamides (e.g. SSFRVGGSRYamide), B-type allatostatins (AST-B; e.g. VPNDWAHFRGSWamide), and orcokinins (e.g. NFDEIDRSSFGFV). The MSI data revealed distribution differences in several neuropeptides (e.g. SGFYANRYamide) between color morphs, but salinity stress appeared to not have a major effect on the localization of the neuropeptides.

  8. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context

    Directory of Open Access Journals (Sweden)

    Joan F. Alonso

    2016-04-01

    Full Text Available Sleep deprivation (SD has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE. Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships.

  9. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context

    Science.gov (United States)

    Alonso, Joan F.; Romero, Sergio; Mañanas, Miguel A.; Alcalá, Marta; Antonijoan, Rosa M.; Giménez, Sandra

    2016-01-01

    Sleep deprivation (SD) has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE). Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships. PMID:27089346

  10. The Effect of Aging on Mitochondrial Complex I and the Extent of Oxidative Stress in the Rat Brain Cortex.

    Science.gov (United States)

    Tatarkova, Zuzana; Kovalska, Maria; Timkova, Veronika; Racay, Peter; Lehotsky, Jan; Kaplan, Peter

    2016-08-01

    One of the characteristic features of the aging is dysfunction of mitochondria. Its role in the regulation of metabolism and apoptosis suggests a possible link between these cellular processes. This study investigates the relationship of respiratory complex I with aging-related oxidative stress in the cerebral mitochondria. Deterioration of complex I seen in senescent (26-months old) mitochondria was accompanied by decline in total thiol group content, increase of HNE and HNE-protein adducts as well as decreased content of complex I subunits, GRIM-19 and NDUFV2. On the other hand, decline of complex I might be related with the mitochondrial apoptosis through increased Bax/Bcl-2 cascade in 15-month old animal brains. Higher amount of Bcl-2, Bcl-xL with the lower content of GRIM-19 could maintain to some extent elevated oxidative stress in mitochondria as seen in the senescent group. In the cortical M1 region increased presence of TUNEL+ cells and more than 20-times higher density of Fluoro-Jade C+ cells in 26-months old was observed, suggesting significant neurodegenerative effect of aging in the neuronal cells. Our study supports a scenario in which the age-related decline of complex I might sensitize neurons to the action of death agonists, such as Bax through lipid and protein oxidative stimuli in mitochondria. Although aging is associated with oxidative stress, these changes did not increase progressively with age, as similar extent of lesions was observed in oxidative stress markers of the both aged groups.

  11. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

    Directory of Open Access Journals (Sweden)

    Tamar ePashut

    2014-06-01

    Full Text Available Although transcranial magnetic stimulation (TMS is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

  12. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context.

    Science.gov (United States)

    Alonso, Joan F; Romero, Sergio; Mañanas, Miguel A; Alcalá, Marta; Antonijoan, Rosa M; Giménez, Sandra

    2016-04-14

    Sleep deprivation (SD) has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE). Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships.

  13. Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

    Directory of Open Access Journals (Sweden)

    Claudia Mastroeni

    Full Text Available Repetitive transcranial magnetic stimulation (rTMS of the human motor hand area (M1HAND can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66met polymorphism in the brain-derived neurotrophic factor (BDNF gene. Here we used theta burst stimulation (TBS to examine whether the BDNF val(66met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS usually inducing a lasting increase and continuous TBS (cTBS a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66met (n = 12 and val(66val (n = 17 carriers received neuronavigated cTBS followed by cTBS (n = 27, cTBS followed by iTBS (n = 29, and iTBS followed by iTBS (n = 28. Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS and increase (iTBS in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66met carriers and val(66val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66met polymorphism, our results do not support the notion that the BDNF val(66met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

  14. Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

    Science.gov (United States)

    Mastroeni, Claudia; Bergmann, Til Ole; Rizzo, Vincenzo; Ritter, Christoph; Klein, Christine; Pohlmann, Ines; Brueggemann, Norbert; Quartarone, Angelo; Siebner, Hartwig Roman

    2013-01-01

    Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val(66)met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66)met (n = 12) and val(66)val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

  15. Sensory neuropeptide effects in human skin.

    OpenAIRE

    Fuller, R W; Conradson, T. B.; Dixon, C M; Crossman, D.C.; Barnes, P. J.

    1987-01-01

    1 Neuropeptides released from sensory nerves may account for cutaneous flare and wheal following local trauma. In 28 normal subjects we have studied the effects of four sensory neuropeptides given by intradermal injection on the forearm or back. 2 All peptides caused a flare distant from the site of injection, presumably due to an axon reflex. Substance P (SP) was the most potent (geometric mean dose causing 50% of maximum flare, 4.2 pmol). Neurokinin A (NKA) was the next most potent with neu...

  16. Neuropeptides in helminths: occurrence and distribution.

    Science.gov (United States)

    Marks, Nikki J; Maule, Aaron G

    2010-01-01

    Nematode neuropeptide systems comprise an exceptionally complex array of approximately 250 peptidic signaling molecules that operate within a structurally simple nervous system of approximately 300 neurons. A relatively complete picture of the neuropeptide complement is available for Caenorhabditis elegans, with 30 flp, 38 ins and 43 nlp genes having been documented; accumulating evidence indicates similar complexity in parasitic nematodes from clades I, III, IV and V. In contrast, the picture for parasitic platyhelminths is less clear, with the limited peptide sequence data available providing concrete evidence for only FMRFamide-like peptide (FLP) and neuropeptide F (NPF) signaling systems, each of which only comprises one or two peptides. With the completion of the Schmidtea meditteranea and Schistosoma mansoni genome projects and expressed sequence tag datasets for other flatworm parasites becoming available, the time is ripe for a detailed reanalysis ofneuropeptide signalingin flatworms. Although the actual neuropeptides provide limited obvious value as targets for chemotherapeutic-based control strategies, they do highlight the signaling systems present in these helminths and provide tools for the discovery of more amenable targets such as neuropeptide receptors or neuropeptide processing enzymes. Also, they offer opportunities to evaluate the potential of their associated signaling pathways as targets through RNA interference (RNAi)-based, target validation strategies. Currently, within both helminth phyla, theflp signaling systems appear to merit further investigation as they are intrinsically linked with motor function, a proven target for successful anti-parasitics; it is clear that some nematode NLPs also play a role in motor function and could have similar appeal. At this time, it is unclear if flatworm NPF and nematode INS peptides operate in pathways that have utility for parasite control. Clearly, RNAi-based validation could be a starting point for

  17. Neuropeptide Y-like signalling and nutritionally mediated gene expression and behaviour in the honey bee.

    Science.gov (United States)

    Ament, S A; Velarde, R A; Kolodkin, M H; Moyse, D; Robinson, G E

    2011-06-01

    Previous research has led to the idea that derived traits can arise through the evolution of novel roles for conserved genes. We explored whether neuropeptide Y (NPY)-like signalling, a conserved pathway that regulates food-related behaviour, is involved in a derived, nutritionally-related trait, the division of labour in worker honey bees. Transcripts encoding two NPY-like peptides were expressed in separate populations of brain neurosecretory cells, consistent with endocrine functions. NPY-related genes were upregulated in the brains of older foragers compared with younger bees performing brood care ('nurses'). A subset of these changes can be attributed to nutrition, but neuropeptide F peptide treatments did not influence sugar intake. These results contrast with recent reports of more robust associations between division of labour and the related insulin-signalling pathway and suggest that some elements of molecular pathways associated with feeding behaviour may be more evolutionarily labile than others.

  18. Cortex Matures Faster in Youths With Highest IQ

    Science.gov (United States)

    ... Current Issue Past Issues Research News From NIH Cortex Matures Faster in Youths With Highest IQ Past ... scans showed that their brains' outer mantle, or cortex, thickens more rapidly during childhood, reaching its peak ...

  19. Effect of Calpain on The Degradation of Tau in Rat Brain Cortex Extracts%Calpain对细胞骨架蛋白tau降解作用的研究

    Institute of Scientific and Technical Information of China (English)

    方征宇; 刘世杰; 王小川; 刘蓉; 王群; 陈正跃; 王建枝

    2003-01-01

    Calpain is a calcium-activated protease and there are two ubiquitously distributed mammalian calpains, namely calpain 1 (μ-calpain and CAPN1) and calpain 2 (m-calpain and CAPN2). Calpains regulate the function of many proteins by limited proteolysis. To determine the nature of different subtypes of calpain on degradation of microtubule-associated protein tau, the rat brain cortex extracts were incubated with 0.2 mmol/L, 1 mmol/L, 3 mmol/L and 5 mmol/L of CaCl2 for 15 min at 37℃. The findings were that Ca2+ treatment at concentration 1~5 mmol/L led to significant proteolysis of tau protein and this degradation was blocked by calpain inhibitor, calpeptin. In addition, when the extracts containing 1 mmol/L CaCl2 were treated with μ-calpain inhibitor (0.05 μmol/L of calpastatin) or m-calpain inhibitor (100 μmol/L calpain inhibitor Ⅳ) or both, the Ca2+-induced degradation of tau protein was decreased to 8.6%,92.5% and 97.8%, respectively. These data suggest that both μ-calpain and m-calpain in brain cortex extracts are activated by Ca2+ and both of them degrade tau protein, although, m-calpain plays a more important role in proteolysis of tau.%Calpain是钙依赖性中性蛋白酶,根据其对钙敏感性的不同,可分为m-和μ-calpain两型.分别用不同浓度CaCl2溶液孵育Wistar大鼠脑皮质匀浆液,并用蛋白质印迹和定量图像分析技术检测不同亚型calpain对tau蛋白的降解作用.研究发现:在37℃用1 mmol/L Ca2+孵育底物15 min,可见tau蛋白明显降解,并在分子质量为29 ku处出现tau蛋白降解片段;当Ca2+浓度为5 mmol/L时,tau蛋白几乎全部被降解;这种tau蛋白降解可被calpain特异性抑制剂完全逆转.进一步的研究发现,分别用μ-calpain抑制剂(0.05 μmol/L calpastatin),m-calpain抑制剂(100 μmol/L calpain inhibitor Ⅳ)或总calpain抑制剂(552 μmol/L calpeptin)与1 mmol/L Ca2+共同孵育Wistar大鼠脑皮质匀浆液,Ca2+激活的tau蛋白降解分别被抑制8.6%,92.5%

  20. The Stressed Female Brain: Neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress

    Directory of Open Access Journals (Sweden)

    Lisa Y. Maeng

    2013-12-01

    Full Text Available Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD, indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL and infralimbic (IL subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. 24h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similar to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful

  1. The stressed female brain: neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress.

    Science.gov (United States)

    Maeng, Lisa Y; Shors, Tracey J

    2013-01-01

    Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD), indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA) is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC) during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL) and infralimbic (IL) subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. About 24 h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similarly to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful life

  2. Neuropeptide Y secretion increases in the paraventricular nucleus in association with increased appetite for food.

    OpenAIRE

    Kalra, S P; Dube, M G; Sahu, A; Phelps, C P; Kalra, P S

    1991-01-01

    Feeding in mammals is a periodic behavior; however, knowledge of how the brain signals an intermittent eating pattern is scanty. Recent indirect evidence indicates that one of the signals encoded in the structure of neuropeptide Y (NPY) is to stimulate robust feeding. Therefore, two series of experiments were undertaken to characterize NPY secretion within the paraventricular nucleus (PVN) in association with eating behavior in the rat. Dynamic changes in NPY concentration in several hypothal...

  3. Neuropeptide Y (NPY) as a therapeutic target for neurodegenerative diseases.

    Science.gov (United States)

    Duarte-Neves, Joana; Pereira de Almeida, Luís; Cavadas, Cláudia

    2016-11-01

    Neuropeptide Y (NPY) and NPY receptors are widely expressed in the mammalian central nervous system. Studies in both humans and rodent models revealed that brain NPY levels are altered in some neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Machado-Joseph disease. In this review, we will focus on the roles of NPY in the pathological mechanisms of these disorders, highlighting NPY as a neuroprotective agent, as a neural stem cell proliferative agent, as an agent that increases trophic support, as a stimulator of autophagy and as an inhibitor of excitotoxicity and neuroinflammation. Moreover, the effect of NPY in some clinical manifestations commonly observed in Alzheimer's disease, Parkinson's disease, Huntington's disease and Machado-Joseph disease, such as depressive symptoms and body weight loss, are also discussed. In conclusion, this review highlights NPY system as a potential therapeutic target in neurodegenerative diseases.

  4. Neuropeptide Y induces torpor-like hypothermia in Siberian hamsters.

    Science.gov (United States)

    Paul, Matthew J; Freeman, David A; Park, Jin Ho; Dark, John

    2005-09-01

    Intracerebroventricular (ICV) injections of neuropeptide Y (NPY) are known to decrease body temperature (Tb) of laboratory rats by 1-3 degrees C. Several NPY pathways in the brain terminate in hypothalamic structures involved in energy balance and thermoregulation. Laboratory rats are homeothermic, maintaining Tb within a narrow range. We examined the effect of ICV injected NPY on Tb in the heterothermic Siberian hamster (Phodopus sungorus), a species that naturally undergoes daily torpor in which Tb decreases by as much as 15-20 degrees C. Minimum effective dose was determined in preliminary testing then various doses of NPY were tested in cold-acclimated Siberian hamsters while food was withheld. NPY markedly reduced Tb in the heterothermic Siberian hamster. In addition, the reduction in Tb in 63% of the observations was sufficient to reach the criterion for daily torpor (Tb Siberian hamster. NPY treatment may be activating hypothalamic systems that normally integrate endogenous torpor-producing signals and initiate torpor.

  5. Inhibition of hypothalamic MCT1 expression increases food intake and alters orexigenic and anorexigenic neuropeptide expression

    Science.gov (United States)

    Elizondo-Vega, Roberto; Cortés-Campos, Christian; Barahona, María José; Carril, Claudio; Ordenes, Patricio; Salgado, Magdiel; Oyarce, Karina; García-Robles, María de los Angeles

    2016-01-01

    Hypothalamic glucosensing, which involves the detection of glucose concentration changes by brain cells and subsequent release of orexigenic or anorexigenic neuropeptides, is a crucial process that regulates feeding behavior. Arcuate nucleus (AN) neurons are classically thought to be responsible for hypothalamic glucosensing through a direct sensing mechanism; however, recent data has shown a metabolic interaction between tanycytes and AN neurons through lactate that may also be contributing to this process. Monocarboxylate transporter 1 (MCT1) is the main isoform expressed by tanycytes, which could facilitate lactate release to hypothalamic AN neurons. We hypothesize that MCT1 inhibition could alter the metabolic coupling between tanycytes and AN neurons, altering feeding behavior. To test this, we inhibited MCT1 expression using adenovirus-mediated transfection of a shRNA into the third ventricle, transducing ependymal wall cells and tanycytes. Neuropeptide expression and feeding behavior were measured in MCT1-inhibited animals after intracerebroventricular glucose administration following a fasting period. Results showed a loss in glucose regulation of orexigenic neuropeptides and an abnormal expression of anorexigenic neuropeptides in response to fasting. This was accompanied by an increase in food intake and in body weight gain. Taken together, these results indicate that MCT1 expression in tanycytes plays a role in feeding behavior regulation. PMID:27677351

  6. Cerebrospinal fluid prohormone processing and neuropeptides stimulating feed intake of dairy cows during early lactation.

    Science.gov (United States)

    Kuhla, Björn; Laeger, Thomas; Husi, Holger; Mullen, William

    2015-02-01

    After parturition, feed intake of dairy cows increases within the first weeks of lactation, but the molecular mechanisms stimulating or delaying the slope of increase are poorly understood. Some of the molecules controlling feed intake are neuropeptides that are synthesized as propeptides and subsequently processed before they bind to specific receptors in feeding centers of the brain. Cerebrospinal fluid surrounds most of the feed intake regulatory centers and contains numerous neuropeptides. In the present study, we used a proteomic approach to analyze the neuropeptide concentrations in cerebrospinal fluid taken from dairy cows between day -18 and -10, and between day +10 and +20 relative to parturition. We found 13 proteins which were only present in samples taken before parturition, 13 proteins which were only present in samples taken after parturition, and 25 proteins which were commonly present, before and after parturition. Among them, differences in pro-neuropeptide Y, proenkephalin-A, neuroendocrine convertase-2, neurosecretory protein VGF, chromogranin-A, and secretogranin-1 and -3 concentrations relative to parturition highlight propeptides and prohormone processings involved in the control of feed intake and energy homeostasis. Scaffold analysis further emphasized an increased tone of endogenous opioids associated with the postparturient increase of feed intake.

  7. Role of neuropeptides in anxiety, stress, and depression: from animals to humans.

    Science.gov (United States)

    Kormos, Viktória; Gaszner, Balázs

    2013-12-01

    Major depression, with its strikingly high prevalence, is the most common cause of disability in communities of Western type, according to data of the World Health Organization. Stress-related mood disorders, besides their deleterious effects on the patient itself, also challenge the healthcare systems with their great social and economic impact. Our knowledge on the neurobiology of these conditions is less than sufficient as exemplified by the high proportion of patients who do not respond to currently available medications targeting monoaminergic systems. The search for new therapeutical strategies became therefore a "hot topic" in neuroscience, and there is a large body of evidence suggesting that brain neuropeptides not only participate is stress physiology, but they may also have clinical relevance. Based on data obtained in animal studies, neuropeptides and their receptors might be targeted by new candidate neuropharmacons with the hope that they will become important and effective tools in the management of stress related mood disorders. In this review, we attempt to summarize the latest evidence obtained using animal models for mood disorders, genetically modified rodent models for anxiety and depression, and we will pay some attention to previously published clinical data on corticotropin releasing factor, urocortin 1, urocortin 2, urocortin 3, arginine-vasopressin, neuropeptide Y, pituitary adenylate-cyclase activating polypeptide, neuropeptide S, oxytocin, substance P and galanin fields of stress research.

  8. Neuropeptide receptor expression in inflammatory bowel disease

    NARCIS (Netherlands)

    Beek, Willy Pascale ter

    2008-01-01

    Inflammatory bowel disease (IBD), i.e. Crohn’s disease and ulcerative colitis are characterized by a chronic inflammation of the gastrointestinal tract. Neuropeptides are involved in the regulation of intestinal motility, chloride secretion and inflammatory response, three processes that are disturb

  9. The evolution and diversity of SALMFamide neuropeptides.

    Science.gov (United States)

    Elphick, Maurice R; Achhala, Sufyan; Martynyuk, Natalia

    2013-01-01

    The SALMFamides are a family of neuropeptides that act as muscle relaxants in echinoderms. Two types of SALMFamides have been identified: L-type (e.g. the starfish neuropeptides S1 and S2) with the C-terminal motif LxFamide (x is variable) and F-type with the C-terminal motif FxFamide. In the sea urchin Strongylocentrotus purpuratus (class Echinoidea) there are two SALMFamide genes, one encoding L-type SALMFamides and a second encoding F-type SALMFamides, but hitherto it was not known if this applies to other echinoderms. Here we report the identification of SALMFamide genes in the sea cucumber Apostichopus japonicus (class Holothuroidea) and the starfish Patiria miniata (class Asteroidea). In both species there are two SALMFamide genes: one gene encoding L-type SALMFamides (e.g. S1 in P. miniata) and a second gene encoding F-type SALMFamides plus one or more L-type SALMFamides (e.g. S2-like peptide in P. miniata). Thus, the ancestry of the two SALMFamide gene types traces back to the common ancestor of echinoids, holothurians and asteroids, although it is not clear if the occurrence of L-type peptides in F-type SALMFamide precursors is an ancestral or derived character. The gene sequences also reveal a remarkable diversity of SALMFamide neuropeptides. Originally just two peptides (S1 and S2) were isolated from starfish but now we find that in P. miniata, for example, there are sixteen putative SALMFamide neuropeptides. Thus, the SALMFamides would be a good model system for experimental analysis of the physiological significance of neuropeptide "cocktails" derived from the same precursor protein.

  10. Brain Basics

    Medline Plus

    Full Text Available ... the brain, which is linked to thought and emotion. It is also linked to reward systems in ... or-flight response and is also involved in emotions and memory. anterior cingulate cortex —Is involved in ...

  11. Brain Basics

    Medline Plus

    Full Text Available ... the brain, which is linked to thought and emotion. It is also linked to reward systems in ... or-flight response and is also involved in emotions and memory. anterior cingulate cortex —Is involved in ...

  12. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

    of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings......The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala...... is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control...

  13. Behavioral Effects of Deep Brain Stimulation of the Anterior Nucleus of Thalamus, Entorhinal Cortex and Fornix in a Rat Model of Alzheimer's Disease

    Institute of Scientific and Technical Information of China (English)

    Chao Zhang; Wen-Han Hu; De-Long Wu; Kai Zhang; Jian-Guo Zhang

    2015-01-01

    Background:Recent clinical and preclinical studies have suggested that deep brain stimulation (DBS) can be used as a tool to enhance cognitive functions.The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit,including the anterior nucleus of thalamus (ANT),the entorhinal cortex (EC),and the fornix (FX),on cognitive behaviors in an Alzheimer's disease (AD) rat model.Methods:Forty-eight rats were subjected to an intrahippocampal injection ofamyloid peptides 1-42 to induce an AD model.Rats were divided into six groups:DBS and sham DBS groups of ANT,EC,and FX.Spatial learning and memory were assessed by the Morris water maze (MWM).Recognition memory was investigated by the novel object recognition memory test (NORM).Locomotor and anxiety-related behaviors were detected by the open field test (OF).By using two-way analysis of variance (ANOVA),behavior differences between the six groups were analyzed.Results:In the MWM,the ANT,EC,and FX DBS groups performed differently in terms of the time spent in the platform zone (F(2.23) =6.04,P < 0.01),the frequency of platform crossing (F(2,23) =11.53,P < 0.001),and the percent time spent within the platform quadrant (F(2,23) =6.29,P < 0.01).In the NORM,the EC and FX DBS groups spent more time with the novel object,although the ANT DBS group did not (F(2,23) =10.03,P < 0.001).In the OF,all of the groups showed a similar total distance moved (F(1.42) =1.14,P =0.29)and relative time spent in the center (F(2,42) =0.56,P =0.58).Conclusions:Our results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently thanANT DBS.In addition,hippocampus-independent recognition memory was enhanced by EC and FX DBS.None of the targets showed side-effects of anxiety or locomotor behaviors.

  14. Characterization of a new fish-derived bioactive neuropeptide involved in bone remodelling. Its physiological function and therapeutic potential.

    Directory of Open Access Journals (Sweden)

    Paula Suarez-Bregua

    2014-04-01

    Full Text Available A complex network of autocrine and paracrine signals, hormones and neuronal factors preserve the structural integrity of the skeleton and regulate mineral metabolism in vertebrates. We have characterized a new neuropeptide belonging to parathyroid hormone (PTH family. PTH family members are known to play a key role in maintaining mineral homeostasis, bone remodeling and in regulating embryonic development of skeleton and other tissues. This new neuropeptide is synthesized by two clusters of neurons located in lateral hypothalamus as showed in whole mount in situ hybridization. The functional characterization of the gene using a stable transgenic line revealed its key role in the regulation of bone mineral density. Moreover, phylogenetic analyses and comparative genomics results of conserved synteny reveal that this new neuropeptide is a new ohnolog of the PTH family present in teleosts and some tetrapods like chicken, but absent in mammals . Our findings suggest a new brain to bone pathway, where neuronal factors from hypothalamus signal to receptors on bone cells promoting bone remodeling. Further investigations about this new neuropeptide system would be relevant for developing therapies for bone mineral disorders in humans, since this neuropeptide has a conserved domain similar to other PTH-related peptides which have anabolic effects on bone.

  15. Functional MR imaging of the primary motor area in patients with brain tumors of the motor cortex. Evaluation with echo-planer imaging on a clinical 1.0 T MR imager

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Yoshie; Nakamura, Mitsugu; Tamaki, Norihiko; Ehara, Kazumasa [Kobe Univ. (Japan). School of Medicine; Kitamura, Junji

    1998-04-01

    The study included 3 healthy volunteers and 8 patients with a brain tumor of the motor cortex. The fMRI study was based on the spin echo (SE) type single shot echo-planer technique. Ten contiguous axial slices consisted of 40-60 echo-planer images acquired during 80-120 seconds of repeated task performances and resting periods. Activation maps were calculated by a Z-score method with thresholding, and interpolated on T1 images and surface anatomy scans. In all cases, areas of a significant signal increase were detected as clusters of several pixels on the precentral gyrus contralateral to the motor task performance. The mean signal change was 3.6{+-}0.9% in normal subjects, and 7.2{+-}4.1% in brain tumor patients. There was no significant difference between the two groups. In 5 brain tumor patients significant displacement of the precentral gyrus was observed on T1- or T2-weighted SE images. Of these, 2 also had marked peritumoral edema spreading over the precentral gyrus. There was no significant difference in the size, or the degree, of signal change between patients with or without compression or edema, nor between patients with and without preoperative motor impairment. During surgical intervention, displacement of the precentral gyrus was observed as had been demonstrated on preoperative images of patients. In all patients the precentral gyrus was preserved in all cases, and no deterioration of motor function occurred. Resolution of the displacement and edema was detected on postoperative MRI. Using the echo-planer technique on a clinical 1.0 T imager fMRI localization of the primary motor cortex was obtained in normal and brain tumor subjects. The activated areas were detected on the precentral gyrus of both groups, and even when there was marked brain compression or edema. It is important to identify and preserve the precentral gyrus during surgery to avoid deterioration of motor function. (K.H.)

  16. Oxytocin and Vasopressin: Linking Pituitary Neuropeptides and their Receptors to Social Neurocircuits

    Directory of Open Access Journals (Sweden)

    Danielle Andrea Baribeau

    2015-09-01

    Full Text Available Oxytocin and vasopressin are pituitary neuropeptides that have been shown to affect social processes in mammals. There is growing interest in these molecules and their receptors as potential precipitants of, and/or treatments for, social deficits in neurodevelopmental disorders, including autism spectrum disorder. Numerous behavioral-genetic studies suggest that there is an association between these peptides and individual social abilities; however, an explanatory model that links hormonal activity at the receptor level to complex human behavior remains elusive. The following review summarizes the known associations between the oxytocin and vasopressin neuropeptide systems and social neurocircuits in the brain. Following a micro- to macro- level trajectory, current literature on the synthesis and secretion of these peptides, and the structure, function and distribution of their respective receptors is first surveyed. Next, current models regarding the mechanism of action of these peptides on microcircuitry and other neurotransmitter systems are discussed. Functional neuroimaging evidence on the acute effects of exogenous administration of these peptides on brain activity is then reviewed. Overall, a model in which the local neuromodulatory effects of pituitary neuropeptides on brainstem and basal forebrain regions strengthen signaling within social neurocircuits proves appealing. However, these findings are derived from animal models; more research is needed to clarify the relevance of these mechanisms to human behavior and treatment of social deficits in neuropsychiatric disorders.

  17. Neuropeptide W: a key player in the homeostatic regulation of feeding and energy metabolism?

    Science.gov (United States)

    Takenoya, Fumiko; Kageyama, Haruaki; Shiba, Kanako; Date, Yukari; Nakazato, Masamitsu; Shioda, Seiji

    2010-07-01

    Neuropeptide W (NPW), recently isolated from porcine hypothalamus, has been identified as the endogenous ligand for both NPBWR1 (GPR7) and NPBWR2 (GPR8), which belong to the orphan G protein-coupled receptor family. NPW is thought to play an important role in the regulation of feeding and drinking behavior, and to be related to the stress response. NPW-containing neurons are localized in several regions of the brain, including the hypothalamus, hippocampus, limbic system, midbrain, and brain stem. Accumulated evidence suggests that hypothalamic neuropeptides, such as neuropeptide Y (NPY), orexin, melanin-concentrating hormone (MCH), and proopiomelanocortin (POMC), are involved in the regulation of feeding behavior and energy homeostasis via neuronal circuits in the hypothalamus. NPW also forms part of the feeding-regulating neuronal circuitry in conjunction with other feeding-regulating peptide-containing neurons within the hypothalamus. We summarize our current understanding of the distribution of NPW and of the neuronal interactions between NPW and the different feeding-regulating peptide-containing neurons. This review also discusses evidence for the dichotomous actions of NPW on energy balance and the potential mechanisms involved.

  18. [Neuropeptides, Cytokines and Thymus Peptides as Effectors of Interactions Between Thymus and Neuroendocrine System].

    Science.gov (United States)

    Torkhovskaya, T I; Belova, O V; Zimina, I V; Kryuchkova, A V; Moskvina, S N; Bystrova, O V; Arion, V Ya; Sergienko, V I

    2015-01-01

    The review presents data on mutual influence of nervous system and thymus, realized through the neuroendocrine-immune interactions. The pres- ence of adrenergic and peptidergic nerves in thymus creates conditions for implementation of the effect of neuropeptides secreted by them. These neuropeptides induce activation of thymus cells receptors and influence on the main processes in thymus, including T-lymphocyte maturation, cytokine and hormones production. In turn, thymuspeptides and/or cytokines, controlled by them, enter the brain and exert influence on neuro- nalfunction, which creates the basis for changes of behavior and homeostasis maintenance in response to infection. Ageing and some infectious, autoimmune, neurodegenerative and cancer diseases are accompanied by distortion of interactions between thymus and central nervous system. Mechanisms of signaling pathways, which determine these interactions, are not revealed yet, and their understanding will promote the development of effective therapeutic strategies.

  19. Spinal astrocytes produce and secrete dynorphin neuropeptides.

    Science.gov (United States)

    Wahlert, Andrew; Funkelstein, Lydiane; Fitzsimmons, Bethany; Yaksh, Tony; Hook, Vivian

    2013-04-01

    Dynorphin peptide neurotransmitters (neuropeptides) have been implicated in spinal pain processing based on the observations that intrathecal delivery of dynorphin results in proalgesic effects and disruption of extracellular dynorphin activity (by antisera) prevents injury evoked hyperalgesia. However, the cellular source of secreted spinal dynorphin has been unknown. For this reason, this study investigated the expression and secretion of dynorphin-related neuropeptides from spinal astrocytes (rat) in primary culture. Dynorphin A (1-17), dynorphin B, and α-neoendorphin were found to be present in the astrocytes, illustrated by immunofluorescence confocal microscopy, in a discrete punctate pattern of cellular localization. Measurement of astrocyte cellular levels of these dynorphins by radioimmunoassays confirmed the expression of these three dynorphin-related neuropeptides. Notably, BzATP (3'-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate) and KLA (di[3-deoxy-D-manno-octulosonyl]-lipid A) activation of purinergic and toll-like receptors, respectively, resulted in stimulated secretion of dynorphins A and B. However, α-neoendorphin secretion was not affected by BzATP or KLA. These findings suggest that dynorphins A and B undergo regulated secretion from spinal astrocytes. These findings also suggest that spinal astrocytes may provide secreted dynorphins that participate in spinal pain processing.

  20. The role of neuropeptides in suicidal behavior: a systematic review.

    Science.gov (United States)

    Serafini, Gianluca; Pompili, Maurizio; Lindqvist, Daniel; Dwivedi, Yogesh; Girardi, Paolo

    2013-01-01

    There is a growing evidence that neuropeptides may be involved in the pathophysiology of suicidal behavior. A critical review of the literature was conducted to investigate the association between neuropeptides and suicidal behavior. Only articles from peer-reviewed journals were selected for the inclusion in the present review. Twenty-six articles were assessed for eligibility but only 22 studies were included. Most studies have documented an association between suicidality and some neuropeptides such as corticotropin-releasing factor (CRF), VGF, cholecystokinin, substance P, and neuropeptide Y (NPY), which have been demonstrated to act as key neuromodulators of emotional processing. Significant differences in neuropeptides levels have been found in those who have attempted or completed suicide compared with healthy controls or those dying from other causes. Despite cross-sectional associations between neuropeptides levels and suicidal behavior, causality may not be inferred. The implications of the mentioned studies were discussed in this review paper.

  1. The Role of Neuropeptides in Suicidal Behavior: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Gianluca Serafini

    2013-01-01

    Full Text Available There is a growing evidence that neuropeptides may be involved in the pathophysiology of suicidal behavior. A critical review of the literature was conducted to investigate the association between neuropeptides and suicidal behavior. Only articles from peer-reviewed journals were selected for the inclusion in the present review. Twenty-six articles were assessed for eligibility but only 22 studies were included. Most studies have documented an association between suicidality and some neuropeptides such as corticotropin-releasing factor (CRF, VGF, cholecystokinin, substance P, and neuropeptide Y (NPY, which have been demonstrated to act as key neuromodulators of emotional processing. Significant differences in neuropeptides levels have been found in those who have attempted or completed suicide compared with healthy controls or those dying from other causes. Despite cross-sectional associations between neuropeptides levels and suicidal behavior, causality may not be inferred. The implications of the mentioned studies were discussed in this review paper.

  2. Sensitive Dependence of Mental Function on Prefrontal Cortex

    OpenAIRE

    Alen J Salerian

    2015-01-01

    This study offers evidence to suggest that both normalcy and psychiatric illness are sensitively dependent upon prefrontal cortex function. In general, the emergence of psychiatric symptoms coincide with diminished influence of prefrontal cortex function. The mediating influence of prefrontal cortex may be independent of molecular and regional brain dysfunctions contributory to psychiatric illness.

  3. Comparison of Caenorhabditis elegans NLP peptides with arthropod neuropeptides.

    Science.gov (United States)

    Husson, Steven J; Lindemans, Marleen; Janssen, Tom; Schoofs, Liliane

    2009-04-01

    Neuropeptides are small messenger molecules that can be found in all metazoans, where they govern a diverse array of physiological processes. Because neuropeptides seem to be conserved among pest species, selected peptides can be considered as attractive targets for drug discovery. Much can be learned from the model system Caenorhabditis elegans because of the availability of a sequenced genome and state-of-the-art postgenomic technologies that enable characterization of endogenous peptides derived from neuropeptide-like protein (NLP) precursors. Here, we provide an overview of the NLP peptide family in C. elegans and discuss their resemblance with arthropod neuropeptides and their relevance for anthelmintic discovery.

  4. Neuropeptides in the Gonads: From Evolution to Pharmacology

    Directory of Open Access Journals (Sweden)

    Nicolette L McGuire

    2010-09-01

    Full Text Available Vertebrate gonads are the sites of synthesis and binding of many peptides that were initially classified as neuropeptides. These gonadal neuropeptide systems are neither well understood in isolation, nor in their interactions with other neuropeptide systems. Further, our knowledge of the control of these gonadal neuropeptides by peripheral hormones that bind to the gonads, and which themselves are under regulation by true neuropeptide systems from the hypothalamus, is relatively meagre. This review discusses the existence of a variety of neuropeptides and their receptors which have been discovered in vertebrate gonads, and the possible way in which such systems could have evolved. We then focus on two key neuropeptides for regulation of the hypothalamo-pituitary-gonadal axis: gonadotropin-releasing hormone (GnRH and gonadotropin-inhibitory hormone (GnIH. Comparative studies have provided us with a degree of understanding as to how a gonadal GnRH system might have evolved, and they have been responsible for the discovery of GnIH and its gonadal counterpart. We attempt to highlight what is known about these two key gonadal neuropeptides, how their actions differ from their hypothalamic counterparts, and how we might learn from comparative studies of them and other gonadal neuropeptides in terms of pharmacology, reproductive physiology and evolutionary biology.

  5. Environmental enrichment induces behavioural disturbances in neuropeptide Y knockout mice.

    Science.gov (United States)

    Reichmann, Florian; Wegerer, Vanessa; Jain, Piyush; Mayerhofer, Raphaela; Hassan, Ahmed M; Fröhlich, Esther E; Bock, Elisabeth; Pritz, Elisabeth; Herzog, Herbert; Holzer, Peter; Leitinger, Gerd

    2016-06-16

    Environmental enrichment (EE) refers to the provision of a complex and stimulating housing condition which improves well-being, behaviour and brain function of laboratory animals. The mechanisms behind these beneficial effects of EE are only partially understood. In the current report, we describe a link between EE and neuropeptide Y (NPY), based on findings from NPY knockout (KO) mice exposed to EE. Relative to EE-housed wildtype (WT) animals, NPY KO mice displayed altered behaviour as well as molecular and morphological changes in amygdala and hippocampus. Exposure of WT mice to EE reduced anxiety and decreased central glucocorticoid receptor expression, effects which were absent in NPY KO mice. In addition, NPY deletion altered the preference of EE items, and EE-housed NPY KO mice responded to stress with exaggerated hyperthermia, displayed impaired spatial memory, had higher hippocampal brain-derived neurotrophic factor mRNA levels and altered hippocampal synaptic plasticity, effects which were not seen in WT mice. Accordingly, these findings suggest that NPY contributes to the anxiolytic effect of EE and that NPY deletion reverses the beneficial effects of EE into a negative experience. The NPY system could thus be a target for "enviromimetics", therapeutics which reproduce the beneficial effects of enhanced environmental stimulation.

  6. Fluorescent ligands for studying neuropeptide receptors by confocal microscopy

    Directory of Open Access Journals (Sweden)

    Beaudet A.

    1998-01-01

    Full Text Available This paper reviews the use of confocal microscopy as it pertains to the identification of G-protein coupled receptors and the study of their dynamic properties in cell cultures and in mammalian brain following their tagging with specific fluorescent ligands. Principles that should guide the choice of suitable ligands and fluorophores are discussed. Examples are provided from the work carried out in the authors' laboratory using custom synthetized fluoresceinylated or BODIPY-tagged bioactive peptides. The results show that confocal microscopic detection of specifically bound fluorescent ligands permits high resolution appraisal of neuropeptide receptor distribution both in cell culture and in brain sections. Within the framework of time course experiments, it also allows for a dynamic assessment of the internalization and subsequent intracellular trafficking of bound fluorescent molecules. Thus, it was found that neurotensin, somatostatin and mu- and delta-selective opioid peptides are internalized in a receptor-dependent fashion and according to receptor-specific patterns into their target cells. In the case of neurotensin, this internalization process was found to be clathrin-mediated, to proceed through classical endosomal pathways and, in neurons, to result in a mobilization of newly formed endosomes from neural processes to nerve cell bodies and from the periphery of cell bodies towards the perinuclear zone. These mechanisms are likely to play an important role for ligand inactivation, receptor regulation and perhaps also transmembrane signaling.

  7. Day-night variations of adenosine and its metabolizing enzymes in the brain cortex of the rat--possible physiological significance for the energetic homeostasis and the sleep-wake cycle.

    Science.gov (United States)

    Chagoya de Sánchez, V; Hernández Múñoz, R; Suárez, J; Vidrio, S; Yáñez, L; Díaz Múñoz, M

    1993-05-28

    The role of adenosine as a metabolic regulator of physiological processes in the brain was studied by measuring its concentrations and the activity of adenosine-metabolizing enzymes: 5'-nucleotidase, S-adenosylhomocysteine hydrolase, adenosine deaminase and adenosine kinase in the cerebral cortex of the rat. Other purine compounds, such as, inosine, hypoxanthine and adenine nucleotides were also studied. The purines' pattern was bimodal with high levels of adenosine, inosine and hypoxanthine during the light period reaching their peak at 12.00 h, 08.00 h and 16.00 h, respectively, and small increments during the night between 02.00 h and 04.00 h. The enzymatic activities showed, in general, an unimodal profile with low activity during the day and high activities at night. The adenine nucleotide profile showed a significant diminution between 12.00 h and 24.00 h. The high adenosine level during the day might be due to a diminution of adenine nucleotide and to the low activity of adenosine-metabolizing enzymes, suggesting an accumulation of the nucleoside. The night increase, although of less magnitude, is simultaneous to high activity of adenosine-metabolizing enzymes and could be due to an increased formation of the nucleoside. The present data and the findings from other authors strongly suggest that adenosine in the brain cortex of the rat can participate at least in two physiological processes: regulation of the sleep-wake cycle and replenishment of the adenine nucleotide pool.

  8. Neuron Types in the Presumptive Primary Somatosensory Cortex of the Florida Manatee (Trichechus manatus latirostris).

    Science.gov (United States)

    Reyes, Laura D; Stimpson, Cheryl D; Gupta, Kanika; Raghanti, Mary Ann; Hof, Patrick R; Reep, Roger L; Sherwood, Chet C

    2015-01-01

    Within afrotherians, sirenians are unusual due to their aquatic lifestyle, large body size and relatively large lissencephalic brain. However, little is known about the neuron type distributions of the cerebral cortex in sirenians within the context of other afrotherians and aquatic mammals. The present study investigated two cortical regions, dorsolateral cortex area 1 (DL1) and cluster cortex area 2 (CL2), in the presumptive primary somatosensory cortex (S1) in Florida manatees (Trichechus manatus latirostris) to characterize cyto- and chemoarchitecture. The mean neuron density for both cortical regions was 35,617 neurons/mm(3) and fell within the 95% prediction intervals relative to brain mass based on a reference group of afrotherians and xenarthrans. Densities of inhibitory interneuron subtypes labeled against calcium-binding proteins and neuropeptide Y were relatively low compared to afrotherians and xenarthrans and also formed a small percentage of the overall population of inhibitory interneurons as revealed by GAD67 immunoreactivity. Nonphosphorylated neurofilament protein-immunoreactive (NPNFP-ir) neurons comprised a mean of 60% of neurons in layer V across DL1 and CL2. DL1 contained a higher percentage of NPNFP-ir neurons than CL2, although CL2 had a higher variety of morphological types. The mean percentage of NPNFP-ir neurons in the two regions of the presumptive S1 were low compared to other afrotherians and xenarthrans but were within the 95% prediction intervals relative to brain mass, and their morphologies were comparable to those found in other afrotherians and xenarthrans. Although this specific pattern of neuron types and densities sets the manatee apart from other afrotherians and xenarthrans, the manatee isocortex does not appear to be explicitly adapted for an aquatic habitat. Many of the features that are shared between manatees and cetaceans are also shared with a diverse array of terrestrial mammals and likely represent highly conserved

  9. Lack of experience-mediated differences in the immunohistochemical expression of blood-brain barrier markers (EBA and GluT-1) during the postnatal development of the rat visual cortex.

    Science.gov (United States)

    Argandoña, Enrike G; Bengoetxea, Harkaitz; Lafuente, José V

    2005-05-12

    The development of the cortical vascular tree depends on functional development. External inputs are an essential requirement in the modeling of the visual cortex, mainly during the critical period, when congruous blood supply is needed. The blood brain barrier (BBB) function regulates the passage of substances between the blood and the brain parenchyma, which is one of the main differential features of central nervous system (CNS) microvessels. The endothelial barrier antigen (EBA) has been reported as a specific marker for the BBB physiological function in rats. We studied the postnatal development of EBA expression in the visual cortex of rats reared under opposite paradigms of visual experience, e.g., standard laboratory conditions, dark rearing, and enriched environment at 14, 21, 28, 35, 42, 49, 56, and 63 days postnatal (dpn). Parallel sections were immunohistochemically processed for endothelial barrier antigen (EBA) and glucose transporter-1 (GluT-1). Total vasculature was quantified by Lycopersicon esculentum (LEA) lectin histochemistry. No differences in EBA expression were found between groups, although quantitative differences were recorded paralleling differences in vascular density. Paradoxically, there was no expression in certain cortical vessels which were GluT-1 immunopositive and positivity was consistent in non-barrier areas such as the pineal gland. These findings were completely independent of age or experimental conditions. Therefore, the role of the EBA antigen in the BBB remains unclear: it has been undeniably linked to vascular permeability, but its presence in non-barrier vessels suggests another vascular function. Although visual experience modifies vascular density in the visual cortex, it has not been shown to have an influence on the maturation of the BBB function.

  10. Brain Basics

    Medline Plus

    Full Text Available ... PTSD) . Prefrontal cortex (PFC) —Seat of the brain's executive functions, such as judgment, decision making, and problem solving. ... brain that, in humans, plays a role in executive functions such as judgment, decision making and problem solving, ...

  11. Homolateral cerebrocortical changes in neuropeptide and receptor expression after minimal cortical infarction.

    Science.gov (United States)

    Van Bree, L; Zhang, F; Schiffmann, S N; Halleux, P; Mailleux, P; Vanderhaeghen, J J

    1995-12-01

    A cortical infarct of 2 mm diameter was obtained in the parietal cortex after a craniotomy, disruption of the dura mater and topical application of 3 M KCl. It has been shown previously that the presence of a small cortical infarct induces an increase in immediate early gene messenger RNA expression followed by an increase in neuropeptide and glutamic acid decarboxylase messenger RNA expression. Glutamate, acting at N-methyl-D-aspartate receptors, is held responsible for these changes, since they are blocked by pretreatment with dizocilpine. In the present study, we have analysed the consequences of the dramatic changes in messenger RNA expression on the level of immediate early gene products c-fos and zif 268, and on that of neuropeptides by using immunohistochemistry. After just 1 h, an increase in c-fos- and zif 268-like immunoreactivity is observed in the entire cortical hemisphere homolateral to the infarct, and is no longer detected after 6 h. An increase in cholecystokinin octapeptide-, substance P-, neuropeptide Y- and somatostatin-like immunoreactivity is observed in the entire cortical hemisphere homolateral to the infarct after three days, and is no longer detected after 30 days. To investigate if these dramatic increases in neuropeptide immunoreactivities may have functional consequences, we studied the level of cholecystokinin receptors by autoradiographic binding using [125I]cholecystokinin-8S and in situ hybridization for the detection of cholecystokinin-b receptor messenger RNA. A decrease in cholecystokinin binding sites and cholecystokinin-b receptor messenger RNA is observed in the entire cortical hemisphere homolateral to the infarct after three days, and is no longer detected after nine days. This study shows that a topical stimulation has diffuse effects, reaching regions far from the site of the lesion, and some of them are still strongly present after nine days. The increase in neuropeptide messenger RNAs is followed by an increase in the

  12. Molecular determinants of dysregulated GABAergic gene expression in the prefrontal cortex of subjects with schizophrenia.

    Science.gov (United States)

    Mellios, Nikolaos; Huang, Hsien-Sung; Baker, Stephen P; Galdzicka, Marzena; Ginns, Edward; Akbarian, Schahram

    2009-06-15

    Prefrontal deficits in gamma-aminobutyric acid (GABA)ergic gene expression, including neuropeptide Y (NPY), somatostatin (SST), and parvalbumin (PV) messenger RNAs (mRNAs), have been reported for multiple schizophrenia cohorts. Preclinical models suggest that a subset of these GABAergic markers (NPY/SST) is regulated by brain-derived neurotrophic factor (BDNF), which in turn is under the inhibitory influence of small noncoding RNAs. However, it remains unclear if these mechanisms are important determinants for dysregulated NPY and SST expression in prefrontal cortex (PFC) of subjects with schizophrenia. Using a postmortem case-control design, the association between BDNF protein, NPY/SST/PV mRNAs, and two BDNF-regulating microRNAs (miR-195 and miR-30a-5p) was determined in samples from the PFC of 20 schizophrenia and 20 control subjects. Complementary studies were conducted in cerebral cortex of mice subjected to antipsychotic treatment or a brain-specific ablation of the Bdnf gene. Subjects with schizophrenia showed deficits in NPY and PV mRNAs. Within-pair differences in BDNF protein levels showed strong positive correlations with NPY and SST and a robust inverse association with miR-195 levels, which in turn were not affected by antipsychotic treatment or genetic ablation of Bdnf. Taken together, these results suggest that prefrontal deficits in a subset of GABAergic mRNAs, including NPY, are dependent on the regional supply of BDNF, which in turn is fine-tuned through a microRNA (miRNA)-mediated mechanism.

  13. Mimetic analogs of three insect neuropeptide classes for pest management

    Science.gov (United States)

    Neuropeptides are potent regulators of critical life processes in insects, but are subjected to rapid degradation by peptidases in the hemolymph (blood), tissues and gut. This limitation can be overcome via replacement of peptidase susceptible portions of the insect neuropeptides to create analogs w...

  14. Mimetic analogs of pyrokinin neuropeptides for pest management

    Science.gov (United States)

    Neuropeptides are potent regulators of critical life processes in insects, but are subjected to rapid degradation by peptidases in the hemolymph (blood), tissues and gut. This limitation can be overcome via replacement of peptidase susceptible portions of the insect neuropeptides to create analogs ...

  15. The neuroendocrine genome : neuropeptides and related signaling peptides

    NARCIS (Netherlands)

    Burbach, JPH

    2016-01-01

    Neuropeptides are small proteinaceous substances which are produced, stored, and released through the regulated secretory route by neurons and act on neural substrates. They represent the most diverse group of signaling molecules in the nervous system. In mammals there are 200–300 neuropeptides know

  16. The neuroendocrine genome : neuropeptides and related signaling peptides

    NARCIS (Netherlands)

    Burbach, JPH|info:eu-repo/dai/nl/068420404

    2016-01-01

    Neuropeptides are small proteinaceous substances which are produced, stored, and released through the regulated secretory route by neurons and act on neural substrates. They represent the most diverse group of signaling molecules in the nervous system. In mammals there are 200–300 neuropeptides know

  17. NPY/neuropeptide Y enhances autophagy in the hypothalamus: a mechanism to delay aging?

    Science.gov (United States)

    Aveleira, Célia A; Botelho, Mariana; Cavadas, Cláudia

    2015-01-01

    Aging was recently described as a life event programmed by the hypothalamus, a key brain region that is crucial for the neuroendocrine interaction between the central nervous system and the periphery. Autophagy impairment is a hallmark of aging, contributing to the aging phenotype and to the aggravation of age-related diseases. Since hypothalamic autophagy decreases with age, strategies to promote autophagy in the hypothalamus may be relevant for control of the aging process. NPY (neuropeptide Y) is an endogenous neuropeptide mainly produced by the hypothalamus. We recently reported, for the first time, that NPY stimulates autophagy in rodent hypothalamus and mediates caloric restriction-induced autophagy in hypothalamic neurons. Moreover, we observed that NPY acts through NPY1R (neuropeptide Y receptor Y1) or NPY5R activation involving a concerted action of different signaling pathways. Since both hypothalamic autophagy and NPY levels decrease with age, modulation of NPY levels could provide new putative therapeutic tools to ameliorate age-related deteriorations and extend longevity.

  18. Oxygen sensing neurons and neuropeptides regulate survival after anoxia in developing C. elegans.

    Science.gov (United States)

    Flibotte, John J; Jablonski, Angela M; Kalb, Robert G

    2014-01-01

    Hypoxic brain injury remains a major source of neurodevelopmental impairment for both term and preterm infants. The perinatal period is a time of rapid transition in oxygen environments and developmental resetting of oxygen sensing. The relationship between neural oxygen sensing ability and hypoxic injury has not been studied. The oxygen sensing circuitry in the model organism C. elegans is well understood. We leveraged this information to investigate the effects of impairments in oxygen sensing on survival after anoxia. There was a significant survival advantage in developing worms specifically unable to sense oxygen shifts below their preferred physiologic range via genetic ablation of BAG neurons, which appear important for conferring sensitivity to anoxia. Oxygen sensing that is mediated through guanylate cyclases (gcy-31, 33, 35) is unlikely to be involved in conferring this sensitivity. Additionally, animals unable to process or elaborate neuropeptides displayed a survival advantage after anoxia. Based on these data, we hypothesized that elaboration of neuropeptides by BAG neurons sensitized animals to anoxia, but further experiments indicate that this is unlikely to be true. Instead, it seems that neuropeptides and signaling from oxygen sensing neurons operate through independent mechanisms, each conferring sensitivity to anoxia in wild type animals.

  19. Central Modulation of Neuroinflammation by Neuropeptides and Energy-Sensing Hormones during Obesity

    Directory of Open Access Journals (Sweden)

    Roger Maldonado-Ruiz

    2017-01-01

    Full Text Available Central nervous system (CNS senses energy homeostasis by integrating both peripheral and autonomic signals and responding to them by neurotransmitters and neuropeptides release. Although it is previously considered an immunologically privileged organ, we now know that this is not so. Cells belonging to the immune system, such as B and T lymphocytes, can be recruited into the CNS to face damage or infection, in addition to possessing resident immunological cells, called microglia. In this way, positive energy balance during obesity promotes an inflammatory state in the CNS. Saturated fatty acids from the diet have been pointed out as powerful candidates to trigger immune response in peripheral system and in the CNS. However, how central immunity communicates to peripheral immune response remains to be clarified. Recently there has been a great interest in the neuropeptides, POMC derived peptides, ghrelin, and leptin, due to their capacity to suppress or induce inflammatory responses in the brain, respectively. These may be potential candidates to treat different pathologies associated with autoimmunity and inflammation. In this review, we will discuss the role of lipotoxicity associated with positive energy balance during obesity in proinflammatory response in microglia, B and T lymphocytes, and its modulation by neuropeptides.

  20. Tissue localization and partial characterization of pheromone biosynthesis activating neuropeptide in Achaea janata

    Indian Academy of Sciences (India)

    V S Ajitha; D Muraleedharan

    2005-03-01

    Female sex pheromone production in certain moth species have been shown to be regulated by a cephalic endocrine peptidic factor: pheromone biosynthesis activating neuropeptide (PBAN), having 33 amino acid residues. Antisera against synthetic Heliothis zea-PBAN were developed. Using these polyclonals, immunoreactivity was mapped in the nervous system of Achaea janata. Three distinct groups of immunopositive secretory neurons were identified in the suboesophageal ganglion; and immunoreactivity was observed in the corpora cardiaca, thoracic and in the abdominal ganglia. From about 6000 brain sub-oesophageal ganglion complexes, the neuropeptide was isolated; and purified sequentially by Sep-pak and reversed phase high performance liquid chromatographic methods. Identity of purified PBAN fraction was confirmed with polyclonal antibody by immunoblotting. Molecular mass of the isolated peptide was determined by matrix-assisted laser desorption/ionization mass spectrometry, and was found to be 3900 Da, same as that of known H. zea-PBAN. Radiochemical bioassay confirmed the pheromonotropic effect of the isolated neuropeptide in this insect.

  1. Quantitative proteomic profiling of membrane proteins from the mouse brain cortex, hippocampus, and cerebellum using the HysTag reagent: mapping of neurotransmitter receptors and ion channels

    DEFF Research Database (Denmark)

    Olsen, Jesper V; Nielsen, Peter Aa; Andersen, Jens R

    2007-01-01

    of recently developed methods for isolation of membrane proteins from 10-20 mg brain tissue [Nielsen, P.Aa., Olsen, J.V., Podtelejnokov, A.V., Andersen, J.R., Mann, M., Wisniewski, J.R., 2005. Proteomic mapping of brain plasma membrane proteins. Mol. Cell. Proteomics 4, 402--408] and the Hys......Analysis of the brain proteome and studying brain diseases through clinical biopsies and animal disease models require methods of quantitative proteomics that are sensitive and allow identification and quantification of low abundant membrane proteins from minute amount of tissue. Taking advantage......Tag-quantification method [Olsen, J.V., Andersen, J.R., Nielsen, P.Aa., Nielsen, M.L., Figeys, D., Mann, M., Wisniewski, J.R., 2004. HysTag---A novel proteomic qualification tool applied to differential analysis of membrane proteins from distinct areas of mouse brain. Mol. Cell. Proteomics 3, 82--92] we performed...

  2. Glucocorticoids are required for meal-induced changes in the expression of hypothalamic neuropeptides.

    Science.gov (United States)

    Uchoa, Ernane Torres; Silva, Lilian Eslaine C M; de Castro, Margaret; Antunes-Rodrigues, Jose; Elias, Lucila L K

    2012-06-01

    Glucocorticoid deficiency is associated with a decrease of food intake. Orexigenic peptides, neuropeptide Y (NPY) and agouti related protein (AgRP), and the anorexigenic peptide proopiomelanocortin (POMC), expressed in the arcuate nucleus of the hypothalamus (ARC), are regulated by meal-induced signals. Orexigenic neuropeptides, melanin-concentrating hormone (MCH) and orexin, expressed in the lateral hypothalamic area (LHA), also control food intake. Thus, the present study was designed to test the hypothesis that glucocorticoids are required for changes in the expression of hypothalamic neuropeptides induced by feeding. Male Wistar rats (230-280 g) were subjected to ADX or sham surgery. ADX animals received 0.9% NaCl in the drinking water, and half of them received corticosterone in the drinking water (B: 25 mg/L, ADX+B). Six days after surgery, animals were fasted for 16 h and they were decapitated before or 2 h after refeeding for brain tissue and blood collections. Adrenalectomy decreased NPY/AgRP and POMC expression in the ARC in fasted and refed animals, respectively. Refeeding decreased NPY/AgRP and increased POMC mRNA expression in the ARC of sham and ADX+B groups, with no effects in ADX animals. The expression of MCH and orexin mRNA expression in the LHA was increased in ADX and ADX+B groups in fasted condition, however there was no effect of refeeding on the expression of MCH and orexin in the LHA in the three experimental groups. Refeeding increased plasma leptin and insulin levels in sham and ADX+B animals, with no changes in leptin concentrations in ADX group, and insulin response to feeding was lower in this group. Taken together, these data demonstrated that circulating glucocorticoids are required for meal-induced changes in NPY, AgRP and POMC mRNA expression in the ARC. The lower leptin and insulin responses to feeding may contribute to the altered hypothalamic neuropeptide expression after adrenalectomy.

  3. Coexpression analysis of nine neuropeptides in the neurosecretory preoptic area of larval zebrafish

    Directory of Open Access Journals (Sweden)

    Ulrich eHerget

    2015-02-01

    Full Text Available The paraventricular nucleus (PVN of the hypothalamus in mammals coordinates neuroendocrine, autonomic and behavioral responses pivotal for homeostasis and the stress response. A large amount of studies in rodents has documented that the PVN contains diverse neuronal cell types which can be identified by the expression of distinct secretory neuropeptides. Interestingly, PVN cell types often coexpress multiple neuropeptides whose relative coexpression level are subject to environment-induced plasticity.Due to their small size and transparency, zebrafish larvae offer the possibility to comprehensively study the development and plasticity of the PVN in large groups of intact animals, yet important anatomical information about the larval zebrafish PVN-homologous region has been missing. Therefore we recently defined the location and borders of the larval neurosecretory preoptic area (NPO as the PVN-homologous region in larval zebrafish based on transcription factor expression and cell type clustering. To identify distinct cell types present in the larval NPO, we also generated a comprehensive 3D map of 9 zebrafish homologs of typical neuropeptides found in the mammalian PVN (arginine vasopressin, corticotropin-releasing hormone, proenkephalin a/b, neurotensin, oxytocin, vasoactive intestinal peptide, cholecystokinin, and somatostatin. Here we extend this chemoarchitectural map to include the degrees of coexpression of two neuropeptides in the same cell by performing systematic pairwise comparisons. Our results allowed the subclassification of NPO cell types, and differences in variability of coexpression profiles suggest potential targets of biochemical plasticity. Thus, this work provides an important basis for the analysis of the development, function, and plasticity of the primary neuroendocrine brain region in larval zebrafish.

  4. Genomic and peptidomic analyses of the neuropeptides from the emerging pest, Drosophila suzukii.

    Science.gov (United States)

    Audsley, Neil; Down, Rachel E; Isaac, R Elwyn

    2015-06-01

    Drosophila suzukii is a highly polyphagous invasive pest which has been recently introduced into Europe and North America, where it is causing severe economic losses through larval infestations of stone and berry fruits. The peptidome of the selected nervous tissues of adult D. suzukii was investigated as a first step in identifying potential targets for the development of novel insecticides. Through in silico analyses of the D. suzukii genome databases 28 neuropeptide families, comprising more than 70 predicted peptides were identified. Using a combination of liquid chromatography and mass spectrometry of tissue extracts, 33 predicted peptides, representing 15 different peptide families were identified by their molecular masses and a total of 17 peptide sequences were confirmed by ion fragmentation. A comparison between the peptides and precursors of D. suzukii and D. melanogaster shows they are highly conserved, with differences only identified in the amino acid sequences of the peptides encoded in the FMRFamide, hugin and ecydysis triggering hormone precursors. All other peptides predicted and identified from D. suzukii appear to be identical to those previously characterized from D. melanogaster. Adipokinetic hormone was only identified in the corpus cardiacum, other peptides present included short neuropeptide F, a pyrokinin and myosuppressin, the latter of which was the only peptide identified from the crop nerve bundle. Peptides present in extracts of the brain and/or thoracico-abdominal ganglion included allatostatins, cardioacceleratory peptide 2b, corazonin, extended FMRFamides, pyrokinins, myoinihibitory peptides, neuropeptide-like precursor 1, SIFamide, short neuropeptide F, kinin, sulfakinins and tachykinin related peptides. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  5. Control of sleep-to-wake transitions via fast aminoacid and slow neuropeptide transmission

    Science.gov (United States)

    Mosqueiro, Thiago; de Lecea, Luis; Huerta, Ramon

    2014-01-01

    The Locus Coeruleus (LC) modulates cortical, subcortical, cerebellar, brainstem and spinal cord circuits and it expresses receptors for neuromodulators that operate in a time scale of several seconds. Evidences from anatomical, electrophysiological and optogenetic experiments have shown that LC neurons receive input from a group of neurons called Hypocretins (HCRTs) that release a neuropeptide called hypocretin. It is less known how these two groups of neurons can be coregulated using GABAergic neurons. Since the time scales of GABAA inhibition is several orders of magnitude faster than the hypocretin neuropeptide effect, we investigate the limits of circuit activity regulation using a realistic model of neurons. Our investigation shows that GABAA inhibition is insufficient to control the activity levels of the LCs. Despite slower forms of GABAA can in principle work, there is not much plausibility due to the low probability of the presence of slow GABAA and lack of robust stability at the maximum firing frequencies. The best possible control mechanism predicted by our modeling analysis is the presence of inhibitory neuropeptides that exert effects in a similar time scale as the hypocretin/orexin. Although the nature of these inhibitory neuropeptides has not been identified yet, it provides the most efficient mechanism in the modeling analysis. Finally, we present a reduced mean-field model that perfectly captures the dynamics and the phenomena generated by this circuit. This investigation shows that brain communication involving multiple time scales can be better controlled by employing orthogonal mechanisms of neural transmission to decrease interference between cognitive processes and hypothalamic functions. PMID:25598695

  6. The Drosophila neuropeptides PDF and sNPF have opposing electrophysiological and molecular effects on central neurons.

    Science.gov (United States)

    Vecsey, Christopher G; Pírez, Nicolás; Griffith, Leslie C

    2014-03-01

    Neuropeptides have widespread effects on behavior, but how these molecules alter the activity of their target cells is poorly understood. We employed a new model system in Drosophila melanogaster to assess the electrophysiological and molecular effects of neuropeptides, recording in situ from larval motor neurons, which transgenically express a receptor of choice. We focused on two neuropeptides, pigment-dispersing factor (PDF) and small neuropeptide F (sNPF), which play important roles in sleep/rhythms and feeding/metabolism. PDF treatment depolarized motor neurons expressing the PDF receptor (PDFR), increasing excitability. sNPF treatment had the opposite effect, hyperpolarizing neurons expressing the sNPF receptor (sNPFR). Live optical imaging using a genetically encoded fluorescence resonance energy transfer (FRET)-based sensor for cyclic AMP (cAMP) showed that PDF induced a large increase in cAMP, whereas sNPF caused a small but significant decrease in cAMP. Coexpression of pertussis toxin or RNAi interference to disrupt the G-protein Gαo blocked the electrophysiological responses to sNPF, showing that sNPFR acts via Gαo signaling. Using a fluorescent sensor for intracellular calcium, we observed that sNPF-induced hyperpolarization blocked spontaneous waves of activity propagating along the ventral nerve cord, demonstrating that the electrical effects of sNPF can cause profound changes in natural network activity in the brain. This new model system provides a platform for mechanistic analysis of how neuropeptides can affect target cells at the electrical and molecular level, allowing for predictions of how they regulate brain circuits that control behaviors such as sleep and feeding.

  7. Neuropeptides as lung cancer growth factors.

    Science.gov (United States)

    Moody, Terry W; Moreno, Paola; Jensen, Robert T

    2015-10-01

    This manuscript is written in honor of the Festschrift for Abba Kastin. I met Abba at a Society for Neuroscience meeting and learned that he was Editor-in-Chief of the Journal Peptides. I submitted manuscripts to the journal on "Neuropeptides as Growth Factors in Cancer" and subsequently was named to the Editorial Advisory Board. Over the past 30 years I have published dozens of manuscripts in Peptides and reviewed hundreds of submitted manuscripts. It was always rewarding to interact with Abba, a consummate professional. When I attended meetings in New Orleans I would sometimes go out to dinner with him at the restaurant "Commanders Palace". When I chaired the Summer Neuropeptide Conference we were honored to have him receive the Fleur Strand Award one year in Israel. I think that his biggest editorial contribution has been the "Handbook of Biologically Active Peptides." I served as a Section Editor on "Cancer/Anticancer Peptides" and again found that it was a pleasure working with him. This review focuses on the mechanisms by which bombesin-like peptides, neurotensin and vasoactive intestinal peptide regulate the growth of lung cancer. Published by Elsevier Inc.

  8. NEUROPEPTIDE Y (NPY) SUPPRESSES ETHANOL DRINKING IN ETHANOL-ABSTINENT, BUT NOT NON-ETHANOL-ABSTINENT, WISTAR RATS

    OpenAIRE

    Gilpin, N.W.; Stewart, R B; Badia-Elder, N.E.

    2008-01-01

    In outbred rats, increases in brain neuropeptide Y (NPY) activity suppress ethanol consumption in a variety of access conditions, but only following a history of ethanol dependence. NPY reliably suppresses ethanol drinking in alcohol-preferring (P) rats and this effect is augmented following a period of ethanol abstinence. The purpose of this experiment was to examine the effects of NPY on 2-bottle choice ethanol drinking and feeding in Wistar rats that had undergone chronic ethanol vapor exp...

  9. Circulating levels of neuropeptides (CGRP, VIP, NPY) in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Strauss, Gitte Irene; Edvinsson, L; Larsen, F S;

    2001-01-01

    The present study investigated the circulating levels and cerebral fluxes of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) and their relation to cerebral blood flow (CBF) during normoventilation and hyperventilation in patients with fulminant...... in FHF than in cirrhosis, 87 (55-218) vs. 29 (21-42) pmol/L, and 11 (6-29) vs. 5 (3-9)pmol/L, respectively. NPY was normal, none of the measures were related to CBF, and there was no detectable net brain fluxes. Hyperventilation did not alter any of the measures. CGRP and VIP in FHF seem to reflect...

  10. Neuropeptide Signaling in Crustaceans Probed by Mass Spectrometry

    Science.gov (United States)

    Liang, Zhidan

    Neuropeptides are one of the most diverse classes of signaling molecules whose identities and functions are not yet fully understood. They have been implicated in the regulation of a wide range of physiological processes, including feeding-related and motivated behaviors, and also environmental adaptations. In this work, improved mass spectrometry-based analytical platforms were developed and applied to the crustacean systems to characterize signaling molecules. This dissertation begins with a review of mass spectrometry-based neuropeptide studies from both temporal- and spatial-domains. This review is then followed by several chapters detailing a few research projects related to the crustacean neuropeptidomic characterization and comparative analysis. The neuropeptidome of crayfish, Orconectes rusticus is characterized for the first time using mass spectrometry-based tools. In vivo microdialysis sampling technique offers the capability of direct sampling from extracellular space in a time-resolved manner. It is used to investigate the secreted neuropeptide and neurotransmitter content in Jonah crab, Cancer borealis, in this work. A new quantitation strategy using alternative mass spectrometry data acquisition approach is developed and applied for the first time to quantify neuropeptides. Coupling of this method with microdialysis enables the study of neuropeptide dynamics concurrent with different behaviors. Proof-of-principle experiments validating this approach have been carried out in Jonah crab, Cancer borealis to study feeding- and circadian rhythm-related neuropeptide changes using micoridialysis in a time-resolved manner. This permits a close correlation between behavioral and neurochemical changes, providing potential candidates for future validation of regulatory roles. In addition to providing spatial information, mass spectrometry imaging (MSI) technique enables the characterization of signaling molecules while preserving the temporal resolution. A

  11. Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin.

    Directory of Open Access Journals (Sweden)

    Theofilos Poutahidis

    Full Text Available Wound healing capability is inextricably linked with diverse aspects of physical fitness ranging from recovery after minor injuries and surgery to diabetes and some types of cancer. Impact of the microbiome upon the mammalian wound healing process is poorly understood. We discover that supplementing the gut microbiome with lactic acid microbes in drinking water accelerates the wound-healing process to occur in half the time required for matched control animals. Further, we find that Lactobacillus reuteri enhances wound-healing properties through up-regulation of the neuropeptide hormone oxytocin, a factor integral in social bonding and reproduction, by a vagus nerve-mediated pathway. Bacteria-triggered oxytocin serves to activate host CD4+Foxp3+CD25+ immune T regulatory cells conveying transplantable wound healing capacity to naive Rag2-deficient animals. This study determined oxytocin to be a novel component of a multi-directional gut microbe-brain-immune axis, with wound-healing capability as a previously unrecognized output of this axis. We also provide experimental evidence to support long-standing medical traditions associating diet, social practices, and the immune system with efficient recovery after injury, sustained good health, and longevity.

  12. Dcf1 regulates neuropeptide expression and maintains energy balance.

    Science.gov (United States)

    Liu, Qiang; Chen, Yu; Li, Qian; Wu, Liang; Wen, Tieqiao

    2017-05-22

    Neuropeptide Y (NPY) is an important neurotransmitter in the brain that plays a pivotal role in food intake and energy storage. Although many studies have focused on these functions, the regulation of NPY expression remains unclear. Here we showed that dendritic cell factor 1 (Dcf1) regulates NPY expression and maintains energy balance. We found that NPY expression is significantly reduced in the hypothalamus of Dcf1 knockout (Dcf1(-/-), KO) mice. In contrast, Dcf1 overexpression significantly increases NPY expression in the cell line. We also found that Dcf1 acts upstream of the NPY gene to regulate NPY expression and modulates the NPY-NPY receptor 1-GABA signal. Notably, we observed a significant increase in the ATP concentration in Dcf1(-/-) mice, suggesting a greater demand for energy in the absence of Dcf1. We studied the relationship between Dcf1 and NPY and revealed that Dcf1 plays a critical role in energy balance. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Antenatal betamethasone produces protracted changes in anxiety-like behaviors and in the expression of microtubule-associated protein 2, brain-derived neurotrophic factor and the tyrosine kinase B receptor in the rat cerebellar cortex.

    Science.gov (United States)

    Pascual, Rodrigo; Valencia, Martina; Bustamante, Carlos

    2015-06-01

    Using classic Golgi staining methods, we previously showed that the administration of synthetic glucocorticoid betamethasone in equivalent doses to those given in cases of human premature birth generates long-term alterations in Purkinje cell dendritic development in the cerebellar cortex. In the present study, we evaluated whether betamethasone alters the immunohistochemical expression of proteins that participate in cerebellar Purkinje cell dendritic development and maintenance, including microtubule-associated protein 2 (MAP2), brain-derived neurotrophic factor (BDNF) and the tyrosine kinase B receptor (TrkB), which are located predominantly in the cerebellar molecular layer where Purkinje cell dendritogenesis occurs. Consistent with our previous Golgi stain studies, we observed that animals prenatally exposed to a single course of betamethasone showed long-term alterations in the expression of MAP2, BDNF and TrkB. Additionally, these protracted molecular changes were accompanied by anxiety-like behaviors in the elevated plus maze and marble burying tests.

  14. No laughing matter: intranasal oxytocin administration changes functional brain connectivity during exposure to infant laughter.

    Science.gov (United States)

    Riem, Madelon M E; van IJzendoorn, Marinus H; Tops, Mattie; Boksem, Maarten A S; Rombouts, Serge A R B; Bakermans-Kranenburg, Marian J

    2012-04-01

    Infant laughter is a rewarding experience. It activates neural reward circuits and promotes parental proximity and care, thus facilitating parent-infant attachment. The neuropeptide oxytocin might enhance the incentive salience of infant laughter by modulating neural circuits related to the perception of infant cues. In a randomized controlled trial with functional magnetic resonance imaging we investigated the influence of intranasally administered oxytocin on functional brain connectivity in response to infant laughter. Blood oxygenation level-dependent responses to infant laughter were measured in 22 nulliparous women who were administered oxytocin and 20 nulliparous women who were administered a placebo. Elevated oxytocin levels reduced activation in the amygdala during infant laughter and enhanced functional connectivity between the amygdala and the orbitofrontal cortex, the anterior cingulate, the hippocampus, the precuneus, the supramarginal gyri, and the middle temporal gyrus. Increased functional connectivity between the amygdala and regions involved in emotion regulation may reduce negative emotional arousal while enhancing the incentive salience of the infant laughter.

  15. NeuroPep: a comprehensive resource of neuropeptides.

    Science.gov (United States)

    Wang, Yan; Wang, Mingxia; Yin, Sanwen; Jang, Richard; Wang, Jian; Xue, Zhidong; Xu, Tao

    2015-01-01

    Neuropeptides play a variety of roles in many physiological processes and serve as potential therapeutic targets for the treatment of some nervous-system disorders. In recent years, there has been a tremendous increase in the number of identified neuropeptides. Therefore, we have developed NeuroPep, a comprehensive resource of neuropeptides, which holds 5949 non-redundant neuropeptide entries originating from 493 organisms belonging to 65 neuropeptide families. In NeuroPep, the number of neuropeptides in invertebrates and vertebrates is 3455 and 2406, respectively. It is currently the most complete neuropeptide database. We extracted entries deposited in UniProt, the database (www.neuropeptides.nl) and NeuroPedia, and used text mining methods to retrieve entries from the MEDLINE abstracts and full text articles. All the entries in NeuroPep have been manually checked. 2069 of the 5949 (35%) neuropeptide sequences were collected from the scientific literature. Moreover, NeuroPep contains detailed annotations for each entry, including source organisms, tissue specificity, families, names, post-translational modifications, 3D structures (if available) and literature references. Information derived from these peptide sequences such as amino acid compositions, isoelectric points, molecular weight and other physicochemical properties of peptides are also provided. A quick search feature allows users to search the database with keywords such as sequence, name, family, etc., and an advanced search page helps users to combine queries with logical operators like AND/OR. In addition, user-friendly web tools like browsing, sequence alignment and mapping are also integrated into the NeuroPep database. Database URL: http://isyslab.info/NeuroPep

  16. Neuromodulatory function of neuropeptides in the normal CNS.

    Science.gov (United States)

    Merighi, Adalberto; Salio, Chiara; Ferrini, Francesco; Lossi, Laura

    2011-12-01

    Neuropeptides are small protein molecules produced and released by discrete cell populations of the central and peripheral nervous systems through the regulated secretory pathway and acting on neural substrates. Inside the nerve cells, neuropeptides are selectively stored within large granular vesicles (LGVs), and commonly coexist in neurons with low-molecular-weight neurotransmitters (acetylcholine, amino acids, and catecholamines). Storage in LGVs is responsible for a relatively slow response to secretion that requires enhanced or repeated stimulation. Coexistence (i.e. the concurrent presence of a neuropeptide with other messenger molecules in individual neurons), and co-storage (i.e. the localization of two or more neuropeptides within individual LGVs in neurons) give rise to a complicated series of pre- and post-synaptic functional interactions with low-molecular-weight neurotransmitters. The typically slow response and action of neuropeptides as compared to fast-neurotransmitters such as excitatory/inhibitory amino acids and catecholamines is also due to the type of receptors that trigger neuropeptide actions onto target cells. Almost all neuropeptides act on G-protein coupled receptors that, upon ligand binding, activate an intracellular cascade of molecular enzymatic events, eventually leading to cellular responses. The latter occur in a time span (seconds or more) considerably longer (milliseconds) than that of low-molecular-weight fast-neurotransmitters, directly operating through ion channel receptors. As reviewed here, combined immunocytochemical visualization of neuropeptides and their receptors at the ultrastructural level and electrophysiological studies, have been fundamental to better unravel the role of neuropeptides in neuron-to-neuron communication.

  17. Differential modifications of synaptic weights during odor rule learning: dynamics of interaction between the piriform cortex with lower and higher brain areas.

    Science.gov (United States)

    Cohen, Yaniv; Wilson, Donald A; Barkai, Edi

    2015-01-01

    Learning of a complex olfactory discrimination (OD) task results in acquisition of rule learning after prolonged training. Previously, we demonstrated enhanced synaptic connectivity between the piriform cortex (PC) and its ascending and descending inputs from the olfactory bulb (OB) and orbitofrontal cortex (OFC) following OD rule learning. Here, using recordings of evoked field postsynaptic potentials in behaving animals, we examined the dynamics by which these synaptic pathways are modified during rule acquisition. We show profound differences in synaptic connectivity modulation between the 2 input sources. During rule acquisition, the ascending synaptic connectivity from the OB to the anterior and posterior PC is simultaneously enhanced. Furthermore, post-training stimulation of the OB enhanced learning rate dramatically. In sharp contrast, the synaptic input in the descending pathway from the OFC was significantly reduced until training completion. Once rule learning was established, the strength of synaptic connectivity in the 2 pathways resumed its pretraining values. We suggest that acquisition of olfactory rule learning requires a transient enhancement of ascending inputs to the PC, synchronized with a parallel decrease in the descending inputs. This combined short-lived modulation enables the PC network to reorganize in a manner that enables it to first acquire and then maintain the rule.

  18. Calretinin, parvalbumin and calbindin immunoreactive interneurons in perirhinal cortex and temporal area Te3V of the rat brain: qualitative and quantitative analyses.

    Science.gov (United States)

    Barinka, Filip; Salaj, Martin; Rybář, Jan; Krajčovičová, Eva; Kubová, Hana; Druga, Rastislav

    2012-02-03

    The perirhinal cortex (PRC) composed of areas 35 and 36 forms an important route for activity transfer between the hippocampus-entorhinal cortex and neocortex. Its function in memory formation and consolidation as well as in the initiation and spreading of epileptic activity was already partially elucidated. We studied the general pattern of calretinin (CR), parvalbumin (PV) and calbindin (CB) immunoreactivity and its corrected relative optical density (cROD) as well as morphological features and density of CR and PV immunoreactive (CR+, PV+) interneurons in the rat PRC. Neighboring neocortical association area Te3V was analyzed as well. The PRC differed from the Te3V in higher CR and lower PV overall immunoreactivity level. On CR immunostained sections, the difference between high cROD value in area 35 and low cROD value in area Te3V reached statistical significance (pinterneurons was expressed as a percentage of the total neurons counts. The percentage of CR+ interneurons was higher in area 35 by comparison with area Te3 (pinterneurons did not significantly differ among the examined areas. In conclusion, the PRC possesses specific interneuronal equipment with unusually high proportion of CR+ interneurons, what might be of importance for the presumed gating function of PRC in normal and diseased states.

  19. Motor Cortex Stimulation in Parkinson's Disease

    OpenAIRE

    Marisa De Rose; Giusy Guzzi; Domenico Bosco; Mary Romano; Serena Marianna Lavano; Massimiliano Plastino; Giorgio Volpentesta; Rosa Marotta; Angelo Lavano

    2012-01-01

    Motor Cortex Stimulation (MCS) is less efficacious than Deep Brain Stimulation (DBS) in Parkinson's disease. However, it might be proposed to patients excluded from DBS or unresponsive to DBS. Ten patients with advanced PD underwent unilateral MCS contralaterally to the worst clinical side. A plate electrode was positioned over the motor cortex in the epidural space through single burr hole after identification of the area with neuronavigation and neurophysiological tests. Clinical assessment...

  20. Expression of Zonula Occludens-1 in Cerebral Cortex Following Traumatic Brain Injury%闭锁小带蛋白-1在脑外伤后皮质中的表达变化

    Institute of Scientific and Technical Information of China (English)

    王涛; 孟颖; 邹冬华; 李正东; 陈忆九; 陶陆阳

    2015-01-01

    目的:观察闭锁小带蛋白-1(zonula occludens-1,ZO-1)在脑外伤后皮质中不同时段的表达变化。方法建立小鼠脑外伤模型,分为脑外伤后1h、3h、6h、12h、24h、3d、7d组,同时设立假手术组及正常对照组。脑皮质中伊文思蓝(Evans blue,EB)含量检测评估血脑屏障通透性,Western印迹法和免疫组织化学染色法检测损伤皮质区ZO-1的表达。结果脑外伤后1 h皮质中EB含量开始增加,伤后1~3 d达高峰,伤后7 d接近正常。 Western印迹法显示,ZO-1在损伤1 h后表达下调,损伤1~3 d达到最低值,损伤7 d后明显回升,但仍低于假手术组和正常对照组。免疫组织化学染色显示,正常脑皮质血管中ZO-1呈强阳性表达,损伤后表达逐渐减弱,损伤3 d后阳性表达几乎消失,之后逐渐恢复。结论 ZO-1在脑外伤后皮质区呈先降低后升高的表达规律,与脑外伤后血脑屏障通透性变化规律呈负相关,为推断脑外伤损伤时间提供了新指标。%Objective To observe the time-course expression of zonula occludens-1 (ZO-1) in cerebral cortex after traumatic brain injury (TBI). Methods The TBI model of mouse was established. The mice were divided in 1 h, 3 h, 6 h, 12 h, 24 h, 3 d, 7 d after TBI, shamand control groups. The permeability of the blood brain barrier was evaluated by measuring the extravasation of Evans blue (EB) dye. The expression of Z O-1 in cerebral cortex in the injured area was detected by western blotting and im-munohistochemistry. Results The extravasation of EBdye of injured cortex gradually increased from 1 h, peaked at 1-3 d and approximately decreased to normal at 7 d after TBI. western blotting revealed that the expression of Z O-1 gradually decreased after 1 h, was at the lowest at 1-3 d, and then significantly increased after 7 d but was still lower than that of normal and shamgroups. The result of immunohisto-chemistry showed that Z O-1 had strong

  1. Transcriptome analysis of neuropeptides and G-protein coupled receptors (GPCRs) for neuropeptides in the brown planthopper Nilaparvata lugens.

    Science.gov (United States)

    Tanaka, Yoshiaki; Suetsugu, Yoshitaka; Yamamoto, Kimiko; Noda, Hiroaki; Shinoda, Tetsuro

    2014-03-01

    The genes encoding neuropeptides, neurohormones and their putative G-protein coupled receptors were identified in the brown planthopper (BPH), Nilaparvata lugens (Stål) by transcriptome analysis (RNA-seq). Forty-eight candidate genes were found to encode neuropeptides or peptide hormones. These include all known insect neuropeptides and neurohormones, with the exception of neuropeptide-like precursor 2 (NPLP2) and trissin. The gene coding for prothoracicotropic hormone (PTTH) was first identified from hemimetabolous insect. A total of 57 putative neuropeptide GPCR genes were identified and phylogenetic analysis showed most of them to be closely related to insect GPCRs. A notable finding was the occurrence of vertebrate hormone receptors, thyrotropin-releasing hormone receptor (TRHR)-like GPCR and parathyroid hormone receptor (PTHR)-like GPCRs. These results suggest that N. lugens possesses the most comprehensive neuropeptide system yet found in insects. Moreover, our findings demonstrate the power of RNA-seq as a tool for analyzing the neuropeptide-related genes in the absence of whole genome sequence information.

  2. Influence of magnetic field onnitric oxide and neuropeptideY in rat adrenal gland

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    We have investigated the effects of magnetic fields on nitric acid (NO) and neuropeptide Y (NPY) on adrenal glands of the rat using NO nitric acid reductase-spec- trophotometry and histochemistry techniques. We found that all cellular layers of the adrenal cortex, including zona glomerulosa, zona fasciculata and zona reticularis were stained by NADPH-d, and some chromaffin cells of the medulla were positive for NPY. Furthermore, magnetic fields increased NO so strongly that high NO levels could be maintained for several hours, as well as some neuroganglion cells in medulla that were double-stained for NPY and NADPH-d. Our data showed that the magnetic field can regulate endocrine and neuroendocrine directly by some action on parenchyma cells, or indirectly by action to NO-ergic, NPY-ergic neurons in the adrenal gland.

  3. De novo discovery of neuropeptides in the genomes of parasitic flatworms using a novel comparative approach.

    Science.gov (United States)

    Koziol, Uriel; Koziol, Miguel; Preza, Matías; Costábile, Alicia; Brehm, Klaus; Castillo, Estela

    2016-10-01

    Neuropeptide mediated signalling is an ancient mechanism found in almost all animals and has been proposed as a promising target for the development of novel drugs against helminths. However, identification of neuropeptides from genomic data is challenging, and knowledge of the neuropeptide complement of parasitic flatworms is still fragmentary. In this work, we have developed an evolution-based strategy for the de novo discovery of neuropeptide precursors, based on the detection of localised sequence conservation between possible prohormone convertase cleavage sites. The method detected known neuropeptide precursors with good precision and specificity in the models Drosophila melanogaster and Caenorhabditis elegans. Furthermore, it identified novel putative neuropeptide precursors in nematodes, including the first description of allatotropin homologues in this phylum. Our search for neuropeptide precursors in the genomes of parasitic flatworms resulted in the description of 34 conserved neuropeptide precursor families, including 13 new ones, and of hundreds of new homologues of known neuropeptide precursor families. Most neuropeptide precursor families show a wide phylogenetic distribution among parasitic flatworms and show little similarity to neuropeptide precursors of other bilaterian animals. However, we could also find orthologs of some conserved bilaterian neuropeptides including pyrokinin, crustacean cardioactive peptide, myomodulin, neuropeptide-Y, neuropeptide KY and SIF-amide. Finally, we determined the expression patterns of seven putative neuropeptide precursor genes in the protoscolex of Echinococcus multilocularis. All genes were expressed in the nervous system with different patterns, indicating a hidden complexity of peptidergic signalling in cestodes.

  4. The Age of Human Cerebral Cortex Neurons

    Energy Technology Data Exchange (ETDEWEB)

    Bhardwaj, R D; Curtis, M A; Spalding, K L; Buchholz, B A; Fink, D; Bjork-Eriksson, T; Nordborg, C; Gage, F H; Druid, H; Eriksson, P S; Frisen, J

    2006-04-06

    The traditional static view of the adult mammalian brain has been challenged by the realization of continuous generation of neurons from stem cells. Based mainly on studies in experimental animals, adult neurogenesis may contribute to recovery after brain insults and decreased neurogenesis has been implicated in the pathogenesis of neurological and psychiatric diseases in man. The extent of neurogenesis in the adult human brain has, however, been difficult to establish. We have taken advantage of the integration of {sup 14}C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral cortex. Together with the analysis of the cortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that whereas non-neuronal cells turn over, neurons in the human cerebral cortex are not generated postnatally at detectable levels, but are as old as the individual.

  5. BDNF and NT-4 differentiate two pathways in the modulation of neuropeptide protein levels in postnatal hippocampal interneurons.

    Science.gov (United States)

    Marty, S; Onténiente, B

    1999-05-01

    Neuropeptide protein levels in hippocampal interneurons exhibit a considerable maturation in postnatal animals. This study characterizes the role of neuronal activity in determining neuropeptide protein levels in postnatal hippocampal interneurons, and the involvement of neurotrophins. In hippocampal slices from 7-day-old rats cultured for 2 weeks, treatment with the gamma-aminobutyric acidA (GABAA) receptor antagonist bicuculline increased the staining intensity and the number of neurons immunoreactive for neuropeptide Y (NPY). An opposite effect was observed when non-N-methyl-d-aspartate (non-NMDA) excitatory transmission was blocked. The effects of either treatment were reversed after return to control medium. These findings were similar to those previously obtained on the effects of activity on somatostatin immunostaining. Blockade of endogenous tyrosine kinase neurotrophin receptors using K252a prevented the effects of bicuculline on NPY- and somatostatin-immunoreactive neurons. Application of exogenous neurotrophin-3 (NT-3) increased NPY and somatostatin protein levels in long-term but not short-term cultures, while nerve growth factor (NGF) had no effect. In contrast, brain-derived neurotrophic factor (BDNF) or neurotrophin-4 (NT-4) did not affect equally NPY and somatostatin immunoreactivity: they mimicked the effects of bicuculline treatment on NPY-immunoreactive neurons, but exerted no conspicuous effect on somatostatin immunostaining. These results indicate that although neuronal activity plays a major role in determining neuropeptide protein levels in postnatal hippocampal interneurons, its effects on different neuropeptides might be exerted through different mechanisms, with or without the mediation of BDNF or NT-4.

  6. Differential Changes in Expression of Stress- and Metabolic-Related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal.

    Directory of Open Access Journals (Sweden)

    Bernadett Pintér-Kübler

    Full Text Available Chronic morphine treatment and naloxone precipitated morphine withdrawal activates stress-related brain circuit and results in significant changes in food intake, body weight gain and energy metabolism. The present study aimed to reveal hypothalamic mechanisms underlying these effects. Adult male rats were made dependent on morphine by subcutaneous implantation of constant release drug pellets. Pair feeding revealed significantly smaller weight loss of morphine treated rats compared to placebo implanted animals whose food consumption was limited to that eaten by morphine implanted pairs. These results suggest reduced energy expenditure of morphine-treated animals. Chronic morphine exposure or pair feeding did not significantly affect hypothalamic expression of selected stress- and metabolic related neuropeptides - corticotropin-releasing hormone (CRH, urocortin 2 (UCN2 and proopiomelanocortin (POMC compared to placebo implanted and pair fed animals. Naloxone precipitated morphine withdrawal resulted in a dramatic weight loss starting as early as 15-30 min after naloxone injection and increased adrenocorticotrophic hormone, prolactin and corticosterone plasma levels in morphine dependent rats. Using real-time quantitative PCR to monitor the time course of relative expression of neuropeptide mRNAs in the hypothalamus we found elevated CRH and UCN2 mRNA and dramatically reduced POMC expression. Neuropeptide Y (NPY and arginine vasopressin (AVP mRNA levels were transiently increased during opiate withdrawal. These data highlight that morphine withdrawal differentially affects expression of stress- and metabolic-related neuropeptides in the rat hypothalamus, while relative mRNA levels of these neuropeptides remain unchanged either in rats chronically treated with morphine or in their pair-fed controls.

  7. Perception of hand movement by mirror reflection evokes brain activation in the motor cortex contralateral to a non-moving hand.

    Science.gov (United States)

    Debnath, Ranjan; Franz, Elizabeth A

    2016-08-01

    We investigated whether perception of hand movement via mirror reflection evokes activation in the motor cortex (M1) contralateral to the non-moving hand (the M1 ipsilateral to the moving hand). Continuous electroencephalography (EEG) was recorded from 14 participants while they performed unimanual extension-flexion hand movements in direct view and mirror view conditions. We measured the lateralized readiness potential (LRP) as a marker of M1 activation in both conditions. Both the direct and mirror view conditions produced LRPs, with the mirror view conditions revealing clear activation in M1 contralateral to the non-moving hand (ipsilateral to the moving hand) during both flexion and extension phases. This unambiguous demonstration of M1 activation in association with a non-moving hand (which is visually-perceived as moving), suggests that perception of movement can directly lead to M1 activation.

  8. Working Memory Performance Is Correlated with Local Brain Morphology in the Medial Frontal and Anterior Cingulate Cortex in Fibromyalgia Patients: Structural Correlates of Pain-Cognition Interaction

    Science.gov (United States)

    Luerding, R.; Weigand, T.; Bogdahn, U.; Schmidt-Wilcke, T.

    2008-01-01

    Fibromyalgia (FM) is a disorder of unknown aetiology, characterized by chronic widespread pain, stiffness and sleep disturbances. In addition, patients frequently complain of memory and attention deficits. Accumulating evidence suggests that FM is associated with CNS dysfunction and with an altered brain morphology. However, few studies have…

  9. Neuroprotective Effect of Portulaca oleraceae Ethanolic Extract Ameliorates Methylmercury Induced Cognitive Dysfunction and Oxidative Stress in Cerebellum and Cortex of Rat Brain.

    Science.gov (United States)

    Sumathi, Thangarajan; Christinal, Johnson

    2016-07-01

    Methylmercury (MeHg) is highly toxic, and its principal target tissue in human is the nervous system, which has made MeHg intoxication a public health concern for many decades. Portulaca oleraceae (purslane), a member of the Portulacaceae family, is widespread as a weed and has been ranked the eighth most common plant in the world. In this study, we sought for potential beneficial effects of Portulaca oleracea ethanolic extract (POEE) against the neurotoxicity induced by MeHg in cerebellum and cortex of rats. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with POEE (4 mg/kg, orally) 1 h prior to the administration of MeHg for 21 days. After MeHg exposure, we determine the mercury concentration by atomic absorption spectroscopy (AAS); mercury content was observed high in MeHg-induced group. POEE reduced the mercury content. We also observed that the activities of catalase, superoxide dismutase, glutathione peroxidase, and the level of glutathione were reduced. The levels of glutathione reductase and thiobarbituric acid reactive substance were found to be increased. The above biochemical changes were found to be reversed with POEE. Behavioral changes like decrease tail flick response, longer immobility time, and decreased motor activity were noted down during MeHg exposure. POEE pretreatment offered protection from these behavioral changes. MeHg intoxication also caused histopathological changes in cerebellum and cortex, which was found to be normalized by treatment with POEE. The present results indicate that POEE has protective effect against MeHg-induced neurotoxicity.

  10. Brain regulation of food intake and appetite: molecules and networks.

    Science.gov (United States)

    Broberger, C

    2005-10-01

    In the clinic, obesity and anorexia constitute prevalent problems whose manifestations are encountered in virtually every field of medicine. However, as the command centre for regulating food intake and energy metabolism is located in the brain, the basic neuroscientist sees in the same disorders malfunctions of a model network for how integration of diverse sensory inputs leads to a coordinated behavioural, endocrine and autonomic response. The two approaches are not mutually exclusive; rather, much can be gained by combining both perspectives to understand the pathophysiology of over- and underweight. The present review summarizes recent advances in this field including the characterization of peripheral metabolic signals to the brain such as leptin, insulin, peptide YY, ghrelin and lipid mediators as well as the vagus nerve; signalling of the metabolic sensors in the brainstem and hypothalamus via, e.g. neuropeptide Y and melanocortin peptides; integration and coordination of brain-mediated responses to nutritional challenges; the organization of food intake in simple model organisms; the mechanisms underlying food reward and processing of the sensory and metabolic properties of food in the cerebral cortex; and the development of the central metabolic system, as well as its pathological regulation in cancer and infections. Finally, recent findings on the genetics of human obesity are summarized, as well as the potential for novel treatments of body weight disorders.

  11. Oxytocin in the prelimbic medial prefrontal cortex reduces anxiety-like behavior in female and male rats.

    Science.gov (United States)

    Sabihi, Sara; Durosko, Nicole E; Dong, Shirley M; Leuner, Benedetta

    2014-07-01

    The neuropeptide oxytocin (OT) is anxiolytic in rodents and humans. However, the specific brain regions where OT acts to regulate anxiety requires further investigation. The medial prefrontal cortex (mPFC) has been shown to play a role in the modulation of anxiety-related behavior. In addition, the mPFC contains OT-sensitive neurons, expresses OT receptors, and receives long range axonal projections from OT-producing neurons in the hypothalamus, suggesting that the mPFC may be a target where OT acts to diminish anxiety. To investigate this possibility, female rats were administered OT bilaterally into the prelimbic (PL) region of the mPFC and anxiety-like behavior assessed. In addition, to determine if the effects of OT on anxiety-like behavior are sex dependent and to evaluate the specificity of OT, male and female anxiety-like behavior was tested following delivery of either OT or the closely related neuropeptide arginine vasopressin (AVP) into the PL mPFC. Finally, the importance of endogenous OT in the regulation of anxiety-like behavior was examined in male and female rats that received PL infusions of an OT receptor antagonist (OTR-A). Overall, even though males and females showed some differences in their baseline levels of anxiety-like behavior, OT in the PL region of the mPFC decreased anxiety regardless of sex. In contrast, neither AVP nor an OTR-A affected anxiety-like behavior in males or females. Together, these findings suggest that although endogenous OT in the PL region of the mPFC does not influence anxiety, the PL mPFC is a site where exogenous OT may act to attenuate anxiety-related behavior independent of sex.

  12. Characterization, tissue distribution, and expression of neuropeptide Y in olive flounder Paralichthys olivaceus

    Science.gov (United States)

    Wang, Qian; Tan, Xungang; Du, Shaojun; Sun, Wei; You, Feng; Zhang, Peijun

    2015-05-01

    Neuropeptide Y (NPY) is a 36-amino acid peptide of the neuropeptide Y family that plays key roles in the regulation of food intake. In this study, we focused on NPY mRNA expression changes around feeding time and during food deprivation in olive flounder. The olive flounder NPY mRNA levels were analyzed in different tissues and a high level of expression was detected in the brain. We also demonstrated a correlation between NPY expression levels in the brain and feeding schedule. NPY expression levels in olive flounder maintained on a daily scheduled feeding regimen increased shortly before feeding and decreased after the scheduled feeding time. Compared with the -1 h group before feeding, NPY expression in the 3 h group after feeding decreased significantly ( PNPY mRNA levels in the 24 h fasted group ( PNPY expression is associated with food intake in olive flounder. This result reveals the function of NPY in regulating food intake and its potential importance in olive flounder aquaculture.

  13. Characterization, tissue distribution and regulation of neuropeptideY in Schizothorax prenanti.

    Science.gov (United States)

    Wei, R; Zhou, C; Yuan, D; Wang, T; Lin, F; Chen, H; Wu, H; Xin, Z; Yang, S; Wang, Y; Chen, D; Liu, J; Gao, Y; Li, Z

    2014-08-01

    In this study, the full-length neuropeptide Y (npy) complementary (c)DNA was cloned in ya fish Schizothorax prenanti. npy cDNA was composed of 789 nucleotides with a 288 nucleotide open reading frame encoding a protein of 96 amino acids. The deduced amino acid sequences contained a 28 amino acids signal peptide followed by a 36 amino acids mature neuropeptide Y (NPY). The npy mRNA was expressed mainly in the brain and eye as detected by real-time quantitative polymerase chain reaction RT-PCR (rt-qPCR). The S. prenanti NPY was detectable from blastulation to hatch, suggesting that npy might be involved in the late embryonic development of S. prenanti. An experiment was conducted to determine the expression profile of npy during feeding of a single meal and during long-term fasting. The expression level of npy in fed fish was significantly decreased at 0.5, 1.5, 3 and 9 h post-feeding (hpf) than in fasting fish. Fasting for 14 days induced an increase in npy messenger (m)RNA expression in the brain. Overall, the results suggest that NPY is a conserved peptide that might be involved in the regulation of feeding and other physiological function in S. prenanti. © 2014 The Fisheries Society of the British Isles.

  14. Dorsal hippocampus: a site of action of neuropeptides on avoidance behavior?

    Science.gov (United States)

    Greidanus, T B; De Wied, D

    1976-01-01

    Vasopressin and ACTH 4-10 induce a dose dependent long-term, respectively short-term inhibition of extinction of a pole jumping avoidance response in animals with sham lesions in the antero-dorsal hippocampus. Small lesions, causing a restricted damage in this area of the brain, partly inhibit the behavioral effect of vasopressin. Extensive lesions in the antero-dorsal hippocampus completely prevent the inhibitory effects of vasopressin and of ACTH 4-10 on extinction of the avoidance response. The extensive lesions in the dorsal hippocampus complex do not interfere with the rate of extinction, but acquisition of the response is retarded. These observations do not allow the conclusion that the hippocampal complex is the locus of action of neuropeptides in relation to avoidance behavior; it is more likely that this brain region is but one site of behavioral action of these hormones, and that the limbic system needs to be intact to permit the neuropeptides to exert their behavioral effects.

  15. Expression of neuropeptide W in rat stomach mucosa: regulation by nutritional status, glucocorticoids and thyroid hormones.

    Science.gov (United States)

    Caminos, Jorge E; Bravo, Susana B; García-Rendueles, María E R; Ruth González, C; Garcés, Maria F; Cepeda, Libia A; Lage, Ricardo; Suárez, Miguel A; López, Miguel; Diéguez, Carlos

    2008-02-07

    Neuropeptide W (NPW) is a recently identified neuropeptide that binds to G-protein-coupled receptor 7 (GPR7) and 8 (GPR8). In rodent brain, NPW mRNA is confined to specific nuclei in hypothalamus, midbrain and brainstem. Expression of NPW mRNA has also been confirmed in peripheral organs such as stomach. Several reports suggested that brain NPW is implicated in the regulation of energy and hormonal homeostasis, namely the adrenal and thyroid axes; however the precise physiological role and regulation of peripheral NPW remains unclear. In this study, we examined the effects of nutritional status on the regulation of NPW in stomach mucosa. Our results show that in this tissue, NPW mRNA and protein expression is negatively regulated by fasting and food restriction, in all the models we studied: males, females and pregnant females. Next, we examined the effect of glucocorticoids and thyroid hormones on NPW mRNA expression in the stomach mucosa. Our data showed that NPW expression is decreased in this tissue after glucocorticoid treatment or hyperthyroidism. Conversely, hypothyroidism induces a marked increase in the expression of NPW in rat stomach. Overall, these data indicate that stomach NPW is regulated by nutritional and hormonal status.

  16. Neuropeptides control the dynamic behavior of airway mucosal dendritic cells.

    Science.gov (United States)

    Voedisch, Sabrina; Rochlitzer, Sabine; Veres, Tibor Z; Spies, Emma; Braun, Armin

    2012-01-01

    The airway mucosal epithelium is permanently exposed to airborne particles. A network of immune cells patrols at this interface to the environment. The interplay of immune cells is orchestrated by different mediators. In the current study we investigated the impact of neuronal signals on key functions of dendritic cells (DC). Using two-photon microscopic time-lapse analysis of living lung sections from CD11c-EYFP transgenic mice we studied the influence of neuropeptides on airway DC motility. Additionally, using a confocal microscopic approach, the phagocytotic capacity of CD11c(+) cells after neuropeptide stimulation was determined. Electrical field stimulation (EFS) leads to an unspecific release of neuropeptides from nerves. After EFS and treatment with the neuropeptides vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP), airway DC in living lung slices showed an altered motility. Furthermore, the EFS-mediated effect could partially be blocked by pre-treatment with the receptor antagonist CGRP(8-37). Additionally, the phagocytotic capacity of bone marrow-derived and whole lung CD11c(+) cells could be inhibited by neuropeptides CGRP, VIP, and Substance P. We then cross-linked these data with the in vivo situation by analyzing DC motility in two different OVA asthma models. Both in the acute and prolonged OVA asthma model altered neuropeptide amounts and DC motility in the airways could be measured. In summary, our data suggest that neuropeptides modulate key features motility and phagocytosis of mouse airway DC. Therefore altered neuropeptide levels in airways during allergic inflammation have impact on regulation of airway immune mechanisms and therefore might contribute to the pathophysiology of asthma.

  17. Omega-3 fatty acid deficiency during brain maturation reduces neuronal and behavioral plasticity in adulthood.

    Directory of Open Access Journals (Sweden)

    Harsharan Singh Bhatia

    Full Text Available Omega-3-fatty acid DHA is a structural component of brain plasma membranes, thereby crucial for neuronal signaling; however, the brain is inefficient at synthesizing DHA. We have asked how levels of dietary n-3 fatty acids during brain growth would affect brain function and plasticity during adult life. Pregnant rats and their male offspring were fed an n-3 adequate diet or n-3 deficient diets for 15 weeks. Results showed that the n-3 deficiency increased parameters of anxiety-like behavior using open field and elevated plus maze tests in the male offspring. Behavioral changes were accompanied by a level reduction in the anxiolytic-related neuropeptide Y-1 receptor, and an increase in the anxiogenic-related glucocorticoid receptor in the cognitive related frontal cortex, hypothalamus and hippocampus. The n-3 deficiency reduced brain levels of docosahexaenoic acid (DHA and increased the ratio n-6/n-3 assessed by gas chromatography. The n-3 deficiency reduced the levels of BDNF and signaling through the BDNF receptor TrkB, in proportion to brain DHA levels, and reduced the activation of the BDNF-related signaling molecule CREB in selected brain regions. The n-3 deficiency also disrupted the insulin signaling pathways as evidenced by changes in insulin receptor (IR and insulin receptor substrate (IRS. DHA deficiency during brain maturation reduces plasticity and compromises brain function in adulthood. Adequate levels of dietary DHA seem crucial for building long-term neuronal resilience for optimal brain performance and aiding in the battle against neurological disorders.

  18. Altered Coupling between Motion-Related Activation and Resting-State Brain Activity in the Ipsilesional Sensorimotor Cortex after Cerebral Stroke

    Directory of Open Access Journals (Sweden)

    Jianping Hu

    2017-07-01

    Full Text Available Functional connectivity maps using resting-state functional magnetic resonance imaging (rs-fMRI can closely resemble task fMRI activation patterns, suggesting that resting-state brain activity may predict task-evoked activation or behavioral performance. However, this conclusion was mostly drawn upon a healthy population. It remains unclear whether the predictive ability of resting-state brain activity for task-evoked activation would change under different pathological conditions. This study investigated dynamic changes of coupling between patterns of resting-state functional connectivity (RSFC and motion-related activation in different stages of cerebral stroke. Twenty stroke patients with hand motor function impairment were involved. rs-fMRI and hand motion-related fMRI data were acquired in the acute, subacute, and early chronic stages of cerebral stroke on a 3-T magnetic resonance (MR scanner. Sixteen healthy participants were enrolled as controls. For each subject, an activation map of the affected hand was first created using general linear model analysis on task fMRI data, and then an RSFC map was determined by seeding at the peak region of hand motion activation during the intact hand task. We then measured the extent of coupling between the RSFC maps and motion-related activation maps. Dynamic changes of the coupling between the two fMRI maps were estimated using one-way repeated measures analysis of variance across the three stages. Moreover, imaging parameters were correlated with motor performances. Data analysis showed that there were different coupling patterns between motion-related activation and RSFC maps associating with the affected motor regions during the acute, subacute, and early chronic stages of stroke. Coupling strengths increased as the recovery from stroke progressed. Coupling strengths were correlated with hand motion performance in the acute stage, while coupling recovery was negatively correlated with the recovery

  19. Neuropeptides of the cotton fleahopper, Pseudatomoscelis seriatus (Reuter).

    Science.gov (United States)

    Predel, Reinhard; Russell, William K; Russell, David H; Suh, Charles P-C; Nachman, Ronald J

    2012-03-01

    The cotton fleahopper, Pseudatomoscelis seriatus (Reuter), is an economically important pest of cotton, and increasing concerns over resistance, detrimental effects on beneficial insects and safety issues associated with traditional insecticide applications have led to an interest in research on novel, alternative strategies for control. One such approach requires a more basic understanding of the neurohormonal system that regulates important physiological properties of the fleahopper; e.g. the expression of specific messenger molecules such as neuropeptides. Therefore we performed a peptidomic study of neural tissues from the fleahopper which led to the first identification of the sequences of native peptide hormones. These peptide hormones include the following neuropeptides: corazonin, short neuropeptide F (sNPF), myosuppressin, CAPA-pyrokinin and CAPA-PVK peptides. The CAPA-pyrokinin, sNPF, and CAPA-PVK peptides represent novel sequences. A comparison of fleahopper neuropeptides with those of related heteropteran species indicates that they are quite different. The sNPF of P. seriatus shows, among others, a novel substitution of Leu with Phe within the C-terminal region; a modification that sets it apart from the known sNPFs of not only other Heteroptera but of other arthropod species as well. The identity of the neuropeptides native to the fleahopper can aid in the potential development of biostable, bioavailable mimetic agonists and antagonists capable of disrupting the physiological functions that these neuropeptides regulate.

  20. Discovery of multiple neuropeptide families in the phylum Platyhelminthes.

    Science.gov (United States)

    McVeigh, Paul; Mair, Gunnar R; Atkinson, Louise; Ladurner, Peter; Zamanian, Mostafa; Novozhilova, Ekaterina; Marks, Nikki J; Day, Tim A; Maule, Aaron G

    2009-09-01

    Available evidence shows that short amidated neuropeptides are widespread and have important functions within the nervous systems of all flatworms (phylum Platyhelminthes) examined, and could therefore represent a starting point for new lead drug compounds with which to combat parasitic helminth infections. However, only a handful of these peptides have been characterised, the rigorous exploration of the flatworm peptide signalling repertoire having been hindered by the dearth of flatworm genomic data. Through searches of both expressed sequence tags and genomic resources using the basic local alignment search tool (BLAST), we describe 96 neuropeptides on 60 precursors from 10 flatworm species. Most of these (51 predicted peptides on 14 precursors) are novel and are apparently restricted to flatworms; the remainder comprise nine recognised peptide families including FMRFamide-like (FLPs), neuropeptide F (NPF)-like, myomodulin-like, buccalin-like and neuropeptide FF (NPFF)-like peptides; notably, the latter have only previously been reported in vertebrates. Selected peptides were localised immunocytochemically to the Schistosoma mansoni nervous system. We also describe several novel flatworm NPFs with structural features characteristic of the vertebrate neuropeptide Y (NPY) superfamily, previously unreported characteristics which support the common ancestry of flatworm NPFs with the NPY-superfamily. Our dataset provides a springboard for investigation of the functional biology and therapeutic potential of neuropeptides in flatworms, simultaneously launching flatworm neurobiology into the post-genomic era.

  1. Anti-anhedonic effect of deep brain stimulation of the prefrontal cortex and the dopaminergic reward system in a genetic rat model of depression: an intracranial self-stimulation paradigm study.

    Science.gov (United States)

    Rea, Ellis; Rummel, Julia; Schmidt, Timo T; Hadar, Ravit; Heinz, Andreas; Mathé, Aleksander A; Winter, Christine

    2014-01-01

    One of the two core symptoms of major depression (MD), whether uni- or bipolar, is the inability to experience pleasure, suggested to be triggered by dysregulation within the brain reward system. In recent years, deep brain stimulation (DBS) has evolved as a potential tool to modulate pathological neural activity; stimulation of the subgenual cingulate (Cg25) has been shown to reduce depressive symptoms, including anhedonia. In rodents, the ventromedial prefrontal cortex (vmPFC) is likely to represent the correlate of Cg25 and accordingly, stimulation of vmPFC reduces anhedonia-like behavior in rats. The present study addresses the question of whether the anti-anhedonic effect of vmPFC-DBS is mediated by the brain reward system. Rats of the Flinders Sensitive Line (FSL), a validated genetic animal model of depression, and its controls, the Flinders Resistant Line (FRL), were stimulated in the vmPFC and tested in the forced swim test (FST), sucrose consumption test (SCT) and the intracranial self-stimulation (ICSS) paradigm. The curve-shift paradigm of ICSS was used in combination with vmPFC-DBS, d-amphetamine and fluoxetine to quantify reward-facilitating or -attenuating treatment effects. Our findings support anti-depressive efficacy of vmPFC-DBS with respect to despair- and anhedonia-like behavior, as shown in the FST and SCT, respectively. However, DBS did not elicit reward-facilitating or reward-attenuating effects on ICSS behavior. These data suggest that it is unlikely that the anti-anhedonic effect of vmPFC-DBS depends on the mesolimbic dopaminergic reward system. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Amygdalar neuropeptide Y Y1 receptors mediate the anxiolytic-like actions of neuropeptide Y in the social interaction test.

    Science.gov (United States)

    Sajdyk, T J; Vandergriff, M G; Gehlert, D R

    1999-03-01

    The effects of intra-amygdalar neuropeptide Y infusions were assessed in rats using the social interaction test. Neuropeptide Y administered into the central nucleus of the amygdala did not alter behavior, while injections into the basolateral nucleus of the amygdala produced an increased social interaction time. Furthermore, the anxiolytic-like effect was antagonized by co-administration of the potent neuropeptide Y Y1 receptor antagonist ((R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]methyl]-N2-(diphen ylacetyl)-argininamide trifluoroacetate) 3304, but not with the inactive enantiomer ((R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]methyl]-N2-(diphen ylacetyl)-argininamide trifluoroacetate) 3457. Therefore, neuropeptide Y produces an anxiolytic-like effect in the social interaction test through neuropetide Y Y1 receptors located in the basolateral amygdala.

  3. Neuropeptide Regulation of Appetite and Reproduction

    Directory of Open Access Journals (Sweden)

    Small CJ

    2004-01-01

    Full Text Available It is now recognised that appropriate regulation of reproduction, energy intake and energy expenditure, and thus maintenance of body weight and fertility, relies on complex hypothalamic neuro-circuitry. Feeding and reproductive function are closely linked. During times of under nourishment and falling body fat the reproductive axis is down regulated. Circulating factors and hypothalamic circuits co-ordinate these responses. Leptin has been described to be an important peripheral signal that indicates body fat stores to the hypothalamus and thus links nutrition and reproduction. Leptin acts by altering neuropeptide circuits in the hypothalamus, which alter gonadotrophin releasing hormone (GnRH release and food intake. The importance of key neuropeptide systems identified in rodents is now being established in man. Notably mutations in the melanocortin MC4 receptor are found in up to 4 % of the morbidly obese whilst in a proportion of patients with anorexia nervosa mutations have been identified in the agoutirelated peptide (AgRP gene, which codes for an endogenous antagonist of this receptor. Intranasal administration of a melanocortin fragment known to activate the MC4 receptor decreases adiposity in humans. The melanocortin system has been shown to influence the reproductive axis in rodents. However, the role of the melanocortin system in the control of reproduction in humans remains to be established. Since the discovery of leptin, attention has also been focused on peripheral signals that regulate reproduction, food intake and energy expenditure, either directly or via feedback on hypothalamic circuits. Notable new discoveries in this area include the gastric hormone ghrelin. Circulating ghrelin stimulates food intake in rodents and humans although an influence on the reproductive axis is yet to be reported. Neuropeptidregulation von Appetit und Reproduktion. Mittlerweile gilt es als anerkannt, daß eine entsprechende Regulation der

  4. Can neuropeptides treat obesity? A review of neuropeptides and their potential role in the treatment of obesity

    OpenAIRE

    Boughton, C K; Murphy, K. G.

    2013-01-01

    Obesity is a major worldwide public health issue. The physiological systems that regulate body weight are thus of great interest as targets for anti-obesity agents. Peptidergic systems are critical to the regulation of energy homeostasis by key regions in the hypothalamus and brainstem. A number of neuropeptide systems have therefore been investigated as potential treatments for obesity. Blocking orexigenic peptide signals such as neuropeptide Y, melanin-concentrating hormone, orexins, relaxi...

  5. The Neuropeptide Corazonin Controls Social Behavior and Caste Identity in Ants.

    Science.gov (United States)

    Gospocic, Janko; Shields, Emily J; Glastad, Karl M; Lin, Yanping; Penick, Clint A; Yan, Hua; Mikheyev, Alexander S; Linksvayer, Timothy A; Garcia, Benjamin A; Berger, Shelley L; Liebig, Jürgen; Reinberg, Danny; Bonasio, Roberto

    2017-08-10

    Social insects are emerging models to study how gene regulation affects behavior because their colonies comprise individuals with the same genomes but greatly different behavioral repertoires. To investigate the molecular mechanisms that activate distinct behaviors in different castes, we exploit a natural behavioral plasticity in Harpegnathos saltator, where adult workers can transition to a reproductive, queen-like state called gamergate. Analysis of brain transcriptomes during the transition reveals that corazonin, a neuropeptide homologous to the vertebrate gonadotropin-releasing hormone, is downregulated as workers become gamergates. Corazonin is also preferentially expressed in workers and/or foragers from other social insect species. Injection of corazonin in transitioning Harpegnathos individuals suppresses expression of vitellogenin in the brain and stimulates worker-like hunting behaviors, while inhibiting gamergate behaviors, such as dueling and egg deposition. We propose that corazonin is a central regulator of caste identity and behavior in social insects. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The Brain-Heart Connection: Frontal Cortex and Left Ventricle Angiotensinase Activities in Control and Captopril-Treated Hypertensive Rats—A Bilateral Study

    Directory of Open Access Journals (Sweden)

    Ana B. Segarra

    2013-01-01

    Full Text Available The model of neurovisceral integration suggests that the frontal cortex (FC and the cardiovascular function are reciprocally and asymmetrically connected. We analyzed several angiotensinase activities in the heart left ventricle (VT of control and captopril-treated SHR, and we search for a relationship between these activities and those determined in the left and right FC. Captopril was administered in drinking water for 4 weeks. Samples from the left VT and from the left and right FC were obtained. Soluble and membrane-bound enzymatic activities were measured fluorometrically using arylamides as substrates. The weight of heart significantly decreased after treatment with captopril, mainly, due to the reduction of the left VT weight. In the VT, no differences for soluble activities were observed between control and treated SHR. In contrast, a generalized significant reduction was observed for membrane-bound activities. The most significant correlations between FC and VT were observed in the right FC of the captopril-treated group. The other correlations, right FC versus VT and left FC versus VT in controls and left FC versus VT in the captopril group, were few and low. These results confirm that the connection between FC and cardiovascular system is asymmetrically organized.

  7. Impact of the chronic arsenic poisoning on the ultraturcture of adult mouse brain temporal lobe cortex%慢性砷中毒对成年小鼠大脑皮质颞叶超微结构的影响

    Institute of Scientific and Technical Information of China (English)

    花伟; 臧贵勇

    2015-01-01

    Objective To observe the changes of the ultrastructure of the temporal lobe cortex for the brains of these mouse with chronic arsenicpoisoning ,to explore the mechanism of arsenic toxicity on the brain .Method 60 healthy adult Kunming mouse ( 30 male and 30 female) were selected and divided into control group ,low and high dose groups . There were 20 mouse in each group . The dye arsenic group respectively with distilled water , 1/5LD50 ,1/50LD50 ,As2 O3 solution to fill the stomach ,for three consecutive months .After building ,canister , based on the determination of arsenic in groups of mice brain ,Nepal’s dyeing were used to observe the cerebral cor‐tex of temporal morphology change ,transmission electronmicroscope to observe the changes of the ultrastructure of the cerebral cortex temporal lobe in mice .Result It might be the type the type of arsenic content in the cerebral cor‐tex was significantly higher than the control group (P<0 .05) .It was observed the decrease in the number of infec‐ted each cortical neurons ,shape was irregular ,intracytoplasmic austenite reduced .It was observed under electron microscope the prion edema groups of nerve cells ,organelles decreased ,mitochondrial cristae fracture and cavity . Conclusion Arsenic poisoning can cause nerve cell pathology and ultrastructure change of cerebral cortex .%目的:观察慢性砷中毒对小鼠大脑皮质颞叶超微结构的改变,探讨砷对大脑的毒性机制。方法选取健康成年昆明小鼠60只,雌雄各半,分为对照组、慢性砷中毒低、高剂量组,每组20只,各染砷组分别以蒸馏水、1/5LD50、1/50 LD50的As2 O3溶液灌胃,连续3个月。经造模、染毒、取材后,测定各组小鼠大脑中砷含量,采用尼氏染色观察大脑皮质颞叶形态学改变,透射电镜观察小鼠大脑皮质颞叶超微结构的变化。结果(1)染毒各组小鼠大脑皮质中砷含量明显高于对照组(P<0.05);(2)

  8. Transient expression of neuropeptide W in postnatal mouse hypothalamus--a putative regulator of energy homeostasis.

    Science.gov (United States)

    Motoike, T; Skach, A G; Godwin, J K; Sinton, C M; Yamazaki, M; Abe, M; Natsume, R; Sakimura, K; Yanagisawa, M

    2015-08-20

    Neuropeptide B and W (NPB and NPW) are cognate peptide ligands for NPBWR1 (GPR7), a G protein-coupled receptor. In rodents, they have been implicated in the regulation of energy homeostasis, neuroendocrine/autonomic responses, and social interactions. Although localization of these peptides and their receptors in adult rodent brain has been well documented, their expression in mouse brain during development is unknown. Here we demonstrate the transient expression of NPW mRNA in the dorsomedial hypothalamus (DMH) of postnatal mouse brain and its co-localization with neuropeptide Y (NPY) mRNA. Neurons expressing both NPW and NPY mRNAs begin to emerge in the DMH at about postnatal day 0 (P-0) through P-3. Their expression is highest around P-14, declines after P-21, and by P-28 only a faint expression of NPW and NPY mRNA remains. In P-18 brains, we detected NPW neurons in the region spanning the subincertal nucleus (SubI), the lateral hypothalamic (LH) perifornical (PF) areas, and the DMH, where the highest expression of NPW mRNA was observed. The majority of these postnatal hypothalamic NPW neurons co-express NPY mRNA. A cross of NPW-iCre knock-in mice with a Cre-dependent tdTomato reporter line revealed that more than half of the reporter-positive neurons in the adult DMH, which mature from the transiently NPW-expressing neurons, are sensitive to peripherally administrated leptin. These data suggest that the DMH neurons that transiently co-express NPW and NPY in the peri-weaning period might play a role in regulating energy homeostasis during postnatal development. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Immunohistochemical localization of oxytocin receptors in human brain.

    Science.gov (United States)

    Boccia, M L; Petrusz, P; Suzuki, K; Marson, L; Pedersen, C A

    2013-12-03

    The neuropeptide oxytocin (OT) regulates rodent, primate and human social behaviors and stress responses. OT binding studies employing (125)I-d(CH2)5-[Tyr(Me)2,Thr4,Tyr-NH2(9)] ornithine vasotocin ((125)I-OTA), has been used to locate and quantify OT receptors (OTRs) in numerous areas of the rat brain. This ligand has also been applied to locating OTRs in the human brain. The results of the latter studies, however, have been brought into question because of subsequent evidence that (125)I-OTA is much less selective for OTR vs. vasopressin receptors in the primate brain. Previously we used a monoclonal antibody directed toward a region of the human OTR to demonstrate selective immunostaining of cell bodies and fibers in the preoptic-anterior hypothalamic area and ventral septum of a cynomolgus monkey (Boccia et al., 2001). The present study employed the same monoclonal antibody to study the location of OTRs in tissue blocks containing cortical, limbic and brainstem areas dissected from fixed adult, human female brains. OTRs were visualized in discrete cell bodies and/or fibers in the central and basolateral regions of the amygdala, medial preoptic area (MPOA), anterior and ventromedial hypothalamus, olfactory nucleus, vertical limb of the diagonal band, ventrolateral septum, anterior cingulate and hypoglossal and solitary nuclei. OTR staining was not observed in the hippocampus (including CA2 and CA3), parietal cortex, raphe nucleus, nucleus ambiguus or pons. These results suggest that there are some similarities, but also important differences, in the locations of OTRs in human and rodent brains. Immunohistochemistry (IHC) utilizing a monoclonal antibody provides specific localization of OTRs in the human brain and thereby provides opportunity to further study OTR in human development and psychiatric conditions. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. [Leu31, Pro34]neuropeptide Y

    DEFF Research Database (Denmark)

    Fuhlendorff, J; Gether, U; Aakerlund, L;

    1990-01-01

    Two types of binding sites have previously been described for 36-amino acid neuropeptide Y (NPY), called Y1 and Y2 receptors. Y2 receptors can bind long C-terminal fragments of NPY-e.g., NPY-(13-36)-peptide. In contrast, Y1 receptors have until now only been characterized as NPY receptors that do...... not bind such fragments. In the present study an NPY analog is presented, [Leu31, Pro34]NPY, which in a series of human neuroblastoma cell lines and on rat PC-12 cells can displace radiolabeled NPY only from cells that express Y1 receptors and not from those expressing Y2 receptors. The radiolabeled analog......, [125I-Tyr36] monoiodo-[Leu31, Pro34]NPY, also binds specifically only to cells with Y1 receptors. The binding of this analog to Y1 receptors on human neuroblastoma cells is associated with a transient increase in cytoplasmic free calcium concentrations similar to the response observed with NPY. [Leu31...

  11. The neuropeptide oxytocin modulates consumer brand relationships.

    Science.gov (United States)

    Fürst, Andreas; Thron, Jesko; Scheele, Dirk; Marsh, Nina; Hurlemann, René

    2015-10-09

    Each year, companies invest billions of dollars into marketing activities to embellish brands as valuable relationship partners assuming that consumer brand relationships (CBRs) and interpersonal relationships rest upon the same neurobiological underpinnings. Given the crucial role of the neuropeptide oxytocin (OXT) in social bonding, this study tests whether OXT-based mechanisms also determine the bond between consumers and brands. We conducted a randomized, placebo-controlled study involving 101 subjects and analyzed the effect of intranasal OXT on consumers' attribution of relationship qualities to brands, brands paired with human celebrity endorsers, and familiar persons. OXT indeed promoted the attribution of relationship qualities not only in the case of social and semi-social stimuli, but also brands. Intriguingly, for subjects scoring high on autistic-like traits, the effect of OXT was completely reversed, evident in even lower relationship qualities across all stimulus categories. The importance of OXT in a CBR context is further corroborated by a three-fold increase in endogenous release of OXT following exposure to one's favorite brand and positive associations between baseline peripheral OXT concentrations and brand relationship qualities. Collectively, our findings indicate that OXT not only plays a fundamental role in developing interpersonal relationships, but also enables relationship formation with objects such as brands.

  12. 不同胎龄人胎脑皮质额叶神经干细胞发育规律%Developmental features of neural stem cells in frontal cortex of embryonic human brain at various ages

    Institute of Scientific and Technical Information of China (English)

    尹晓娟; 封志纯

    2005-01-01

    BACKGROUND: Neural stem cells(NSCs) have been used to treat brain injury or some degenerating diseases of nervous system. Since in vitro culture conditions for NSCs differ from normal physiological conditions, whether the properties of the cultured cells are consistent with those of cells under physiological conditions? Therefore, inducing endogenous NSCs to proliferate and differentiate may be more promising for practise of NSCs.OBJECTIVE: This study was designed to investigate the developmental properties of NSCs in frontal cortex of embryonic human brain at various ages.DESIGN: It was a randomized experimental study.SETTING: This study was conducted at Department of Pediatrics, Zhujiang Hospital, Southern Medical University.PARTICIPANTS: Totally 90 16-to-36-week-old fetuses underwent inducing abortion by water bag were selected at the Obstetrics & Gynecology Department of Zhujiang Hospital Affiliated to Southern Medical University from October 2003 to March 2004. Brain tissue was taken from the frontal cortex of the aborted fetuses. All the mothers had normal physical examination findings. The informed consents on inducing abortion by water bag had been obtained from relatives and the mothers. The study was conducted with a prior permission from the competent department of the First Military Medical University. According to their ages, the fetuses were divided into 6 groups,16-week group, 20-week group, 24-week group, 28-week group and 36-week group, each group containing 15 cases.METHODS: After inducing abortion by water bag, under axenic conditions, the aborted fetus was dissected, with the scalp excisd, the skull opened and the membrane covering brain pull apart. Then the frontal cerebral cortex was taken out, fixed and sliced. Employing immunohistochemical staining and light microscope, distribution, morphological features, phenotypes, growth patterns and quantity of NSCs in the frontal cortex were observed. Morphological features of the cells and

  13. Brain Basics

    Medline Plus

    Full Text Available ... These factors may act alone or together in complex ways, to change the way a gene is ... improve treatments for anxiety disorders like phobias or post-traumatic stress disorder (PTSD) . Prefrontal cortex (PFC) —Seat of the brain's ...

  14. Brain Basics

    Medline Plus

    Full Text Available ... cell that contains DNA and information the cell needs for growing, staying alive, and making new neurons. prefrontal cortex —A highly developed area at the front of the brain that, in humans, plays a role in executive functions such as ...

  15. Molecular cloning, expression and identification of the promoter regulatory region for the neuropeptide trissin in the nervous system of the silkmoth Bombyx mori.

    Science.gov (United States)

    Roller, Ladislav; Čižmár, Daniel; Gáliková, Zuzana; Bednár, Branislav; Daubnerová, Ivana; Žitňan, Dušan

    2016-06-01

    Trissin has recently been identified as a conserved insect neuropeptide, but its cellular expression and function is unknown. We detected the presence of this neuropeptide in the silkworm Bombyx mori using in silico search and molecular cloning. In situ hybridisation was used to examine trissin expression in the entire central nervous system (CNS) and gut of larvae, pupae and adults. Surprisingly, its expression is restricted to only two pairs of small protocerebral interneurons and four to five large neurons in the frontal ganglion (FG). These neurons were further characterised by subsequent multiple staining with selected antibodies against insect neuropeptides. The brain interneurons innervate edges of the mushroom bodies and co-express trissin with myoinhibitory peptides (MIP) and CRF-like diuretic hormones (CRF-DH). In the FG, one pair of neurons co-express trissin with calcitonin-like diuretic hormone (CT-DH), short neuropeptide F (sNPF) and MIP. These neurons innervate the brain tritocerebrum and musculature of the anterior midgut. The other pair of trissin neurons in the FG co-express sNPF and project axons to the tritocerebrum and midgut. We also used the baculovirus expression system to identify the promoter regulatory region of the trissin gene for targeted expression of various molecular markers in these neurons. Dominant expression of trissin in the FG indicates its possible role in the regulation of foregut-midgut contractions and food intake.

  16. Re-purposing of histological tissue sections for corroborative western blot analysis of hypothalamic metabolic neuropeptide expression following delineation of transactivated structures by Fos immuno-mapping.

    Science.gov (United States)

    Alenazi, Fahaad S H; Ibrahim, Baher A; Briski, Karen P

    2015-04-01

    Fos immunocytochemistry is a valuable anatomical mapping tool for distinguishing cells within complex tissues that undergo genomic activation, but it is seldom paired with corroborative molecular analytical techniques. Due to preparatory requirements that include protein cross-linking for specimen sectioning, histological tissue sections are regarded as unsuitable for those methods. Our studies show that pharmacological activation of the hindbrain energy sensor AMPK by AICAR elicits estradiol (E)-dependent patterns of Fos immunolabeling of hypothalamic metabolic loci. Here, Western blotting was applied to hypothalamic tissue removed from histological sections of E- versus oil (O)-implanted ovariectomized (OVX) female rat brain to measure levels of metabolic transmitters associated with Fos-positive structures. In both E and O rats, AICAR treatment elicited alterations in pro-opiomelanocortin, neuropeptide Y, SF-1, and orexin-A neuropeptide expression that coincided with patterns of Fos labeling of structures containing neurons that synthesize these neurotransmitters, e.g. arcuate and ventromedial nuclei and lateral hypothalamic area. O, but not E animals also exhibited parallel augmentation of tissue corticotropin-releasing hormone neuropeptide levels and paraventricular nucleus Fos staining. Data demonstrate the utility of immunoblot analysis as a follow-through technique to capitalize on Fos mapping of transactivation sites in the brain. Findings that induction of Fos immunoreactivity coincides with adjustments in hypothalamic metabolic neuropeptide expression affirms that this functional indicator reflects changes in neurotransmission in pathways governing metabolic outflow. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Regulation of sleep by neuropeptide Y-like system in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Chunxia He

    Full Text Available Sleep is important for maintenance of normal physiology in animals. In mammals, neuropeptide Y (NPY, a homolog of Drosophila neuropeptide F (NPF, is involved in sleep regulation, with different effects in human and rat. However, the function of NPF on sleep in Drosophila melanogaster has not yet been described. In this study, we investigated the effects of NPF and its receptor-neuropeptide F receptor (NPFR1 on Drosophila sleep. Male flies over-expressing NPF or NPFR1 exhibited increased sleep during the nighttime. Further analysis demonstrated that sleep episode duration during nighttime was greatly increased and sleep latency was significantly reduced, indicating that NPF and NPFR1 promote sleep quality, and their action on sleep is not because of an impact of the NPF signal system on development. Moreover, the homeostatic regulation of flies after sleep deprivation was disrupted by altered NPF signaling, since sleep deprivation decreased transcription of NPF in control flies, and there were less sleep loss during sleep deprivation and less sleep gain after sleep deprivation in flies overexpressing NPF and NPFR1 than in control flies, suggesting that NPF system auto-regulation plays an important role in sleep homeostasis. However, these effects did not occur in females, suggesting a sex-dependent regulatory function in sleep for NPF and NPFR1. NPF in D1 brain neurons showed male-specific expression, providing the cellular locus for male-specific regulation of sleep by NPF and NPFR1. This study brings a new understanding into sleep studies of a sexually dimorphic regulatory mode in female and male flies.

  18. Mice with early retinal degeneration show differences in neuropeptide expression in the suprachiasmatic nucleus

    Directory of Open Access Journals (Sweden)

    Brown R Lane

    2010-07-01

    Full Text Available Abstract Background In mammals, the brain clock responsible for generating circadian rhythms is located in the suprachiasmatic nucleus (SCN of the hypothalamus. Light entrainment of the clock occurs through intrinsically photosensitive retinal ganglion cells (ipRGCs whose axons project to the SCN via the retinohypothalamic tract. Although ipRGCs are sufficient for photoentrainment, rod and cone photoreceptors also contribute. Adult CBA/J mice, which exhibit loss of rod and cone photoreceptors during early postnatal development, have greater numbers of ipRGCs compared to CBA/N control mice. A greater number of photosensitive cells might argue for enhanced light responses, however, these mice exhibit attenuated phase shifting behaviors. To reconcile these findings, we looked for potential differences in SCN neurons of CBA/J mice that might underly the altered circadian behaviors. We hypothesized that CBA/J mice have differences in the expression of neuropeptides in the SCN, where ipRGCs synapse. The neuropeptides vasoactive intestinal peptide (VIP and vasopressin (VP are expressed by many SCN neurons and play an important role in the generation of circadian rhythms and photic entrainment. Methods Using immunohistochemistry, we looked for differences in the expression of VIP and VP in the SCN of CBA/J mice, and using a light-induced FOS assay, we also examined the degree of retinal innervation of the SCN by ipRGCs. Results Our data demonstrate greater numbers of VIP-and VP-positive cells in the SCN of CBA/J mice and a greater degree of light-induced FOS expression. Conclusions These results implicate changes in neuropeptide expression in the SCN which may underlie the altered circadian responses to light in these animals.

  19. Modulatory effects of N-acetylcysteine on cerebral cortex and cerebellum regions of ageing rat brain Efectos moduladores de la N-acetilcisteína sobre la corteza cerebral y las regiones cerebelosas sobre la del cerebro senescente de rata

    Directory of Open Access Journals (Sweden)

    S. Singh Kanwar

    2007-02-01

    Full Text Available Oxidative stress has been implicated in brain ageing and in age-related neurodegenerative disorders. Since Nacetylcysteine (NAC has recently been shown to prevent oxidative damage in ageing brain, we have examined the effects of this thiolic antioxidant on the age associated oxidative stress related parameters in rat brain regions. The lipid peroxide formation, reduced glutathione (GSH content along with the activities of superoxide dismutase (SOD and catalase were determined in the cerebral cortex and cerebellum brain regions of the young (4 months and older (14 months female rats. The lipid peroxidation was observed to be increased in the cerebral cortex regions accompanied by simultaneous decrease in the GSH content in both the regions of older rats. The SOD activity was reduced in both the regions while catalase was reduced only in cerebellum region of the older rats. Following NAC supplementation (160 mg/kg. b. wt./ day, lipid peroxidation was observed to be reduced which was accompanied by enhanced GSH levels, along with enhanced SOD and catalase in both the brain regions of older rats. Further, in the younger rats the NAC treatment resulted in the decrease of lipid peroxidation in both the regions that was accompanied by the increase catalase activity in cerebral cortex region along with increase in GSH content and SOD in cerebellum regions. Our result suggests that the normal brain ageing is associated with the decrease in antioxidative defense status and the supplementation of thiol antioxidants like NAC may prove helpful in managing the age related brain disorders characterized by compromised antioxidative defense systems.El estrés oxidativo se ha implicado en el envejecimiento cerebral y en los trastornos neurodegenerativos asociados con la edad. Puesto que recientemente se ha demostrado que la N-acetilcisteína (NAC previene el daño oxidativo en el cerebro senescente, hemos explorado los efectos de este antioxidante tiólico sobre

  20. The positive effects of high-frequency right dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation on memory, correlated with increases in brain metabolites detected by proton magnetic resonance spectroscopy in recently detoxified alcohol-dependent patients

    Directory of Open Access Journals (Sweden)

    Qiao J

    2016-09-01

    Full Text Available Jun Qiao,1,2 Guixing Jin,1,2 Licun Lei,3 Lan Wang,1,2 Yaqiang Du,3 Xueyi Wang1,2 1Institute of Mental Health, The First Hospital of Hebei Medical University, 2Brain Ageing and Cognitive Neuroscience Laboratory, Hebei Medical University, 3Department of Radiology, The First Hospital of Hebei Medical University, Hebei, People’s Republic of China Objective: To explore the effect of right dorsolateral prefrontal cortex (DLPFC repetitive transcranial magnetic stimulation (rTMS on memory, and its correlation with levels of hippocampal brain metabolites detected by proton magnetic resonance spectroscopy (1H-MRS in recently detoxified alcohol-dependent patients. Materials and methods: In this randomized, double-blind sham-controlled trial, alcohol-dependent patients were enrolled and randomized into two groups: the experimental group (rTMS, 10 Hz, on right DLPFC, 20 sessions and the control group (sham stimulation. Memory function was assessed using Hopkins Verbal Learning Test-Revised (HVLT-R and Brief Visuospatial Memory Test-Revised (BVMT-R before and after treatment. 1H-MRS was used to detect the levels of N-acetyl aspartic acid (NAA, choline (Cho, and creatine (Cr in bilateral hippocampi before and after treatment. Results: Thirty-eight patients (18 in the experimental group and 20 in the control group were included in the analyses. The experimental group showed significantly greater changes in HVLT-R, BVMT-R, NAA/Cr, and Cho/Cr after rTMS from baseline than the control group. The percentage change in BVMT-R and HVLT-R correlated with the percentage change in NAA/Cr and Cho/Cr in the right brain. Conclusion: High-frequency right DLPFC rTMS was associated with improvement in memory dysfunction, which is correlated with levels of hippocampal brain metabolites detected by 1H-MRS in recently detoxified alcohol-dependent patients. Keywords: alcohol dependence, memory, repetitive transcranial magnetic stimulation, MR spectroscopy

  1. CB1 cannabinoid receptors are involved in neuroleptic-induced enhancement of brain neurotensin

    Directory of Open Access Journals (Sweden)

    Parichehr Hassanzadeh

    2014-03-01

    Full Text Available Objective(s: Targeting the neuropeptide systems has been shown to be useful for the development of more effective antipsychotic drugs. Neurotensin, an endogenous neuropeptide, appears to be involved in the mechanism of action of antipsychotics. However, the available data provide conflicting results and the mechanism(s by which antipsychotics affect brain neurotensin neurotransmission have not been identified. Therefore, we aimed to investigate the effects of fluphenazine and amisulpride on brain regional contents of neurotensin considering the role of cannabinoid CB1 receptors which interact with neurotensin neurotransmission. Materials and Methods:Fluphenazine (0.5, 1, and 3 mg/kg or amisulpride (3, 5, and 10 mg/kg were administered intraperitoneally to male Wistar rats either for one day or 28 consecutive days.Twenty four hours after the last injection of drug or vehicle, neurotensin contents were determined in the mesocorticolimbic and nigrostriatal dopamine regions by radioimmunoassay. In the case of any significant change, the effect of pre-treatment with CB1 receptor antagonist, AM251 was investigated. Results:Chronic, but not acute, treatment with the highest dose of fluphenazine or amisulpride resulted in significant enhancement of neurotensin contents in the prefronatal cortex and nucleus accumbens. Fluphenazine also elevated neurotensin levels in the anterior and posterior caudate nuclei and substantia nigra. Neither amisulpride nor fluphenazine affected neurotensin contents in the amygdala or hippocampus. Pre-treatment with AM251 (3 mg/kg prevented the neuroleptic-induced elevation of neurotensin. AM251 showed no effect by itself. Conclusion:The brain neurotensin under the regulatory action of CB1 receptors is involved in[T1]  the effects of amisulpride and fluphenazine.

  2. Food related processes in the insular cortex

    Directory of Open Access Journals (Sweden)

    Sabine eFrank

    2013-08-01

    Full Text Available The insular cortex is a multimodal brain region with regional cytoarchitectonic differences indicating various functional specializations. As a multisensory neural node, the insular cortex integrates perception, emotion, interoceptive awareness, cognition, and gustation. Regarding the latter, predominantly the anterior part of the insular cortex is regarded as the primary taste cortex.In this review, we will specifically focus on the involvement of the insula in food processing and on multimodal integration of food-related items. Influencing factors of insular activation elicited by various foods range from calorie-content to the internal physiologic state, body mass index or eating behavior. Sensory perception of food-related stimuli including seeing, smelling, and tasting elicits increased activation in the anterior and mid-dorsal part of the insular cortex. Apart from the pure sensory gustatory processing, there is also a strong association with the rewarding/hedonic aspects of food items, which is reflected in higher insular activity and stronger connections to other reward-related areas. Interestingly, the processing of food items has been found to elicit different insular activation in lean compared to obese subjects and in patients suffering from an eating disorder (anorexia nervosa, bulimia nervosa. The knowledge of functional differences in the insular cortex opens up the opportunity for possible noninvasive treatment approaches for obesity and eating disorders. To target brain functions directly, real-time functional magnetic resonance imaging neurofeedback offers a state-of-the-art tool to learn to control the anterior insular cortex activity voluntarily. First evidence indicates that obese adults have an enhanced ability to regulate the anterior insular cortex.

  3. Orexin-A expression in dissociated neuronal cultures of the newborn rat cortex

    NARCIS (Netherlands)

    Stoyanova, I.; Feber, le J.; Wiertz, R.W.F.; Rutten, W.L.C.

    2009-01-01

    Orexin A is a neuropeptide isolated from a small group of neurons in the hypothalamus, which orchestrates many different brain functions. Despite the extensive information about orexin A expression and function in the nervous system of adults, data about the formation and maturation of the orexin sy

  4. Microglia in the Cerebral Cortex in Autism

    Science.gov (United States)

    Tetreault, Nicole A.; Hakeem, Atiya Y.; Jiang, Sue; Williams, Brian A.; Allman, Elizabeth; Wold, Barbara J.; Allman, John M.

    2012-01-01

    We immunocytochemically identified microglia in fronto-insular (FI) and visual cortex (VC) in autopsy brains of well-phenotyped subjects with autism and matched controls, and stereologically quantified the microglial densities. Densities were determined blind to phenotype using an optical fractionator probe. In FI, individuals with autism had…

  5. Oxytocin blurs the self-other distinction during trait judgments and reduces medial prefrontal cortex respo