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Sample records for brain cortex neuropeptides

  1. Neuropeptide Y receptors in rat brain: autoradiographic localization

    International Nuclear Information System (INIS)

    Martel, J.C.; St-Pierre, S.; Quirion, R.

    1986-01-01

    Neuropeptide Y (NPY) receptor binding sites have been characterized in rat brain using both membrane preparations and receptor autoradiography. Radiolabelled NPY binds with high affinity and specificity to an apparent single class of sites in rat brain membrane preparations. The ligand selectivity pattern reveals strong similarities between central and peripheral NPY receptors. NPY receptors are discretely distributed in rat brain with high densities found in the olfactory bulb, superficial layers of the cortex, ventral hippocampus, lateral septum, various thalamic nuclei and area postrema. The presence of high densities of NPY and NPY receptors in such areas suggests that NPY could serve important functions as a major neurotransmitter/neuromodulator in the central nervous system

  2. Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

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    de Backer Marijke WA

    2010-08-01

    Full Text Available Abstract Background Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion. Results We fused the signal peptide from the Von Willebrand Factor (VWF to a furin site followed by a processed form of the Agouti related protein (AgRP, AgRP83-132 or α-melanocyte stimulating hormone. In vitro, these minigenes were secreted and biologically active. Additionally, the proteins of the minigenes were not transported into projections of primary neurons, thereby ensuring local release. In vivo administration of VWF-AgRP83-132 , using an adeno-associated viral vector as a delivery vehicle, into the paraventricular hypothalamus increased body weight and food intake of these rats compared to rats which received a control vector. Conclusions This study demonstrated that removal of the N-terminal part of full length AgRP and addition of a VWF signal peptide is a successful strategy to deliver neuropeptide minigenes to the brain and establish local neuropeptide secretion.

  3. Neuropeptide Mapping of Dimmed Cells of Adult Drosophila Brain

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    Diesner, Max; Predel, Reinhard; Neupert, Susanne

    2018-05-01

    Neuropeptides are structurally highly diverse messenger molecules that act as regulators of many physiological processes such as development, metabolism, reproduction or behavior in general. Differentiation of neuropeptidergic cells often corresponds with the presence of the transcription factor DIMMED. In the central nervous system of the fruit fly Drosophila melanogaster, DIMMED commonly occurs in neuroendocrine neurons that release peptides as neurohormones but also in interneurons with complex branching patterns. Fly strains with green fluorescence protein (GFP)-expressing dimmed cells make it possible to systematically analyze the processed neuropeptides in these cells. In this study, we mapped individual GFP-expressing neurons of adult D. melanogaster from the dimmed ( c929)>GFP line. Using single cell mass spectrometry, we analyzed 10 types of dimmed neurons from the brain/gnathal ganglion. These cells included neuroendocrine cells with projection into the retrocerebral complex but also a number of large interneurons. Resulting mass spectra not only provided comprehensive data regarding mature products from 13 neuropeptide precursors but also evidence for the cellular co-localization of neuropeptides from different neuropeptide genes. The results can be implemented in a neuroanatomical map of the D. melanogaster brain. [Figure not available: see fulltext.

  4. Neuropeptide Mapping of Dimmed Cells of Adult Drosophila Brain

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    Diesner, Max; Predel, Reinhard; Neupert, Susanne

    2018-01-01

    Neuropeptides are structurally highly diverse messenger molecules that act as regulators of many physiological processes such as development, metabolism, reproduction or behavior in general. Differentiation of neuropeptidergic cells often corresponds with the presence of the transcription factor DIMMED. In the central nervous system of the fruit fly Drosophila melanogaster, DIMMED commonly occurs in neuroendocrine neurons that release peptides as neurohormones but also in interneurons with complex branching patterns. Fly strains with green fluorescence protein (GFP)-expressing dimmed cells make it possible to systematically analyze the processed neuropeptides in these cells. In this study, we mapped individual GFP-expressing neurons of adult D. melanogaster from the dimmed (c929)>GFP line. Using single cell mass spectrometry, we analyzed 10 types of dimmed neurons from the brain/gnathal ganglion. These cells included neuroendocrine cells with projection into the retrocerebral complex but also a number of large interneurons. Resulting mass spectra not only provided comprehensive data regarding mature products from 13 neuropeptide precursors but also evidence for the cellular co-localization of neuropeptides from different neuropeptide genes. The results can be implemented in a neuroanatomical map of the D. melanogaster brain. [Figure not available: see fulltext.

  5. 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.

  6. 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.

  7. Hyperthyroidism differentially regulates neuropeptide S system in the rat brain.

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    González, Carmen R; Martínez de Morentin, Pablo B; Martínez-Sánchez, Noelia; Gómez-Díaz, Consuelo; Lage, Ricardo; Varela, Luis; Diéguez, Carlos; Nogueiras, Rubén; Castaño, Justo P; López, Miguel

    2012-04-23

    Thyroid hormones play an important role in the regulation of energy balance, sleep and emotional behaviors. Neuropeptide S (NPS) is a recently discovered neuropeptide, regulating feeding, sleep and anxiety. Here, we examined the effect of hyperthyroidism on the gene and protein expression of neuropeptide S and its receptor (NPS-R) in the hypothalamus, brainstem and amygdala of rats. Our results showed that the expression of NPS and NPS-R was differentially modulated by hyperthyroidism in the rat brain. NPS and NPS-R mRNA and protein levels were decreased in the hypothalamus of hyperthyroid rats. Conversely NPS-R expression was highly increased in the brainstem and NPS and NPS-R expression were unchanged in the amygdala of these rats. These data suggest that changes in anxiety and food intake patterns observed in hyperthyroidism could be associated with changes in the expression of NPS and NPS-R. Thus, the NPS/NPS-R system may be involved in several hyperthyroidism-associated comorbidities. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Neuropeptide Y binding sites in rat brain identified with purified neuropeptide Y-I125

    International Nuclear Information System (INIS)

    Walker, M.W.; Miller, R.J.

    1986-01-01

    Neuropeptide Y (NPY) is a widely distributed neuronally localized peptide with 36 amino acids, 5 of which are tyrosines. The authors wished to investigate the properties of specific receptors for NPY. They therefore labeled the tyrosines with I125 using chloramine T and then purified the peptide using HPLC. A single mono-iodinated species of NPY which yielded > 85% specific binding in rat forebrain synaptosomes was selected as the ligand for all subsequent experiments. A time course of binding showed that equilibrium conditions were reached in 60 minutes at 21 0 C. Scatchard plots revealed a single class of binding sites with a Kd and a Bmax of 3 x 10-10 M and 28 pmol/mg, respectively. Competition binding with unlabeled NPY showed 50% displacement of bound ligand at 1 x 10-10 M NPY. Competition binding with rat pancreatic polypeptide (RPP), a homologous peptide possessing little NPY-like activity, showed 50% displacement of bound ligand at 2 x 10 -7 M RPP. No binding was observed on F-11 or PC12 neuronal cell lines, or on HSWP fibroblast cells. They conclude that NPY-I125 purified to homogeneity with HPLC is a highly selective ligand for NPY receptor sites. They are currently investigating such sites in brain, gut, and other tissues

  9. 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

    2017-12-01

    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.

  10. Anxiety-like behavior in transgenic mice with brain expression of neuropeptide Y.

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    Inui, A; Okita, M; Nakajima, M; Momose, K; Ueno, N; Teranishi, A; Miura, M; Hirosue, Y; Sano, K; Sato, M; Watanabe, M; Sakai, T; Watanabe, T; Ishida, K; Silver, J; Baba, S; Kasuga, M

    1998-01-01

    Neuropeptide Y (NPY), one of the most abundant peptide transmitters in the mammalian brain, is assumed to play an important role in behavior and its disorders. To understand the long-term modulation of neuronal functions by NPY, we raised transgenic mice created with a novel central nervous system (CNS) neuron-specific expression vector of human Thy- gene fragment linked to mouse NPY cDNA. In situ hybridization analysis demonstrated transgene-derived NPY expression in neurons (e.g., in the hippocampus, cerebral cortex, and the arcuate nucleus of the hypothalamus) in the transgenic mice. The modest increase of NPY protein in the brain was demonstrated by semiquantitative immunohistochemical analysis and by radioreceptor assay (115% in transgenic mice compared to control littermates). Double-staining experiments indicated colocalization of the transgene-derived NPY message and NPY protein in the same neurons, such as in the arcuate nucleus. The transgenic mice displayed behavioral signs of anxiety and hypertrophy of adrenal zona fasciculata cells, but no change in food intake was observed. The anxiety-like behavior of transgenic mice was reversed, at least in part, by administration of corticotropin-releasing factor (CRF) antagonists, alpha-helical CRF9-41, into the third cerebral ventricle. These results suggest that NPY has a role in anxiety and behavioral responses to stress partly via the CRF neuronal system. This genetic model may provide a unique opportunity to study human anxiety and emotional disorders.

  11. Neuropeptide Y-immunoreactive neurons in the cerebral cortex of humans and other haplorrhine primates

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    Raghanti, Mary Ann; Conley, Tiffini; Sudduth, Jessica; Erwin, Joseph M.; Stimpson, Cheryl D.; Hof, Patrick R.; Sherwood, Chet C.

    2012-01-01

    We examined the distribution of neurons immunoreactive for neuropeptide Y (NPY) in the posterior part of the superior temporal cortex (Brodmann's area 22 or area Tpt) of humans and nonhuman haplorrhine primates. NPY has been implicated in learning and memory and the density of NPY-expressing cortical neurons and axons is reduced in depression, bipolar disorder, schizophrenia, and Alzheimer's disease. Due to the role that NPY plays in both cognition and neurodegenerative diseases, we tested the hypothesis that the density of cortical and interstitial neurons expressing NPY was increased in humans relative to other primate species. The study sample included great apes (chimpanzee and gorilla), Old World monkeys (pigtailed macaque, moor macaque, and baboon) and New World monkeys (squirrel monkey and capuchin). Stereologic methods were used to estimate the density of NPY-immunoreactive (-ir) neurons in layers I-VI of area Tpt and the subjacent white matter. Adjacent Nissl-stained sections were used to calculate local densities of all neurons. The ratio of NPY-ir neurons to total neurons within area Tpt and the total density of NPY-ir neurons within the white matter were compared among species. Overall, NPY-ir neurons represented only an average of 0.006% of the total neuron population. While there were significant differences among species, phylogenetic trends in NPY-ir neuron distributions were not observed and humans did not differ from other primates. However, variation among species warrants further investigation into the distribution of this neuromodulator system. PMID:23042407

  12. Neuropeptide Y (NPY) and peptide YY (PYY) receptors in rat brain

    International Nuclear Information System (INIS)

    Ohkubo, T.; Niwa, M.; Yamashita, K.; Kataoka, Y.; Shigematsu, K.

    1990-01-01

    1. Specific binding sites for neuropeptide Y (NPY) and peptide YY (PYY) were investigated in rat brain areas using quantitative receptor autoradiography with 125 I-Bolton-Hunter NPY ( 125 I-BH-NPY) and 125 I-PYY, radioligands for PP-fold family peptides receptors. 2. There were no differences between localization of 125 I-BH-NPY and 125 I-PYY binding sites in the rat brain. High densities of the binding sites were present in the anterior olfactory nucleus, lateral septal nucleus, stratum radiatum of the hippocampus, posteromedial cortical amygdaloid nucleus, and area postrema. 3. In cold ligand-saturation experiments done in the presence of increasing concentrations of unlabeled NPY and PYY, 125 I-BH-NPY and 125 I-PYY binding to the stratum radiatum of the hippocampus, layer I of the somatosensory frontoparietal cortex, molecular layer of the cerebellum, and area postrema was single and of a high affinity. There was a significant difference between the affinities of 125 I-BH-NPY (Kd = 0.96 nM) and 125 I-PYY binding (Kd = 0.05 nM) to the molecular layer of the cerebellum. The binding of the two radioligands to the other areas examined had the same affinities. 4. When comparing the potency of unlabeled rat pancreatic polypeptide (rPP), a family peptide of NPY and PYY, to inhibit the binding to the areas examined, rPP displaced 125 I-BH-NPY and 125 I-PYY binding to the area postrema more potently than it did the binding to the stratum radiatum of the hippocampus, layer I of the somatosensory frontoparietal cortex, and molecular layer of the cerebellum. 5. Thus, the quantitative receptor autoradiographic method with 125 I-BH-NPY and 125 I-PYY revealed differences in binding characteristics of specific NPY and PYY binding sites in different areas of the rat brain. The results provide further evidence for the existence of multiple NPY-PYY receptors in the central nervous system

  13. MALDI Imaging Analysis of Neuropeptides in Africanized Honeybee (Apis mellifera) Brain: Effect of Aggressiveness.

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    Pratavieira, Marcel; Menegasso, Anally Ribeiro da Silva; Esteves, Franciele Grego; Sato, Kenny Umino; Malaspina, Osmar; Palma, Mario Sérgio

    2018-05-18

    The aggressiveness in honeybees seems to be regulated by multiple genes, under the influence of different factors, such as polyethism of workers, environmental factors, and response to alarm pheromones, creating a series of behavioral responses. It is suspected that neuropeptides seem to be involved with the regulation of the aggressive behavior. The role of allatostatin and tachykinin-related neuropeptides in honeybee brain during the aggressive behavior is unknown; thus, worker honeybees were stimulated to attack and to sting leather targets hanged in front of the colonies. The aggressive individuals were collected and immediately frozen in liquid nitrogen; the heads were removed, and sliced at sagittal plan. The brain slices were submitted to MALDI-Spectral-Imaging analysis, and the results of the present study reported the processing of the precursors proteins into mature forms of the neuropeptides AmAST A (59-76) (AYTYVSEYKRLPVYNFGL-NH2), AmAST A (69-76) (LPVYNFGL-NH2), AmTRP (88 - 96) (APMGFQGMR-NH2), and AmTRP (254 - 262) (ARMGFHGMR-NH2), which apparently acted in different neuropils of honeybee brain, during the aggressive behavior, possibly playing the neuromodulation of different aspects of this complex behavior. These results were biologically validated performing aggressiveness-related behavioral assays, using young honeybee workers that received 1 ng of AmAST A (69-76) or AmTRP (88 - 96) via hemocele. The young workers that were not expected to be aggressive individuals, presented a complete series of the aggressive behaviors, in presence of the neuropeptides, corroborating the hypothesis that correlates the presence of mature AmASTs A and AmTRPs in honeybee brain with the aggressiveness of this insect.

  14. 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...... of incoming neurotransmission, controlling neuronal activity of NPS-producing neurons. Stress-induced functional activation of NPS-producing neurons was detected by staining for the immediate-early gene c-fos, thus supporting earlier findings that NPS might be part of the brain stress response network....

  15. 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.

  16. Development of neuropeptide Y (NPY) immunoreactive neurons in the rat occipital cortex: A combined immunohistochemical-autoradiographic study

    International Nuclear Information System (INIS)

    Cavanagh, M.E.; Parnavelas, J.G.

    1990-01-01

    The postnatal development of neuropeptide Y (NPY)-immunoreactive neurons, previously labeled with [3H]thymidine on embryonic days E14-E21, has been studied in the rat occipital cortex. Immunohistochemistry combined with autoradiography showed evidence of a modified inside-out pattern of maturation. NPY-neurons are generated between E14 and E20 and are found in layers II-VI of the cortex and the subcortical white matter. NPY neurons from all these birthdates are overproduced at first, although cells generated at E16 produce the greatest excess, followed by E15 and E17. Some of these transient neurons are found in the wrong layer for their birthdates, and their elimination produces a more correct alignment at maturity. However, most of the NPY neurons that survive are generated at E17, and these cells are found throughout layers II-VI with a preponderance in layer VI. This evidence is strongly suggestive of cell death rather than merely cessation of production of NPY

  17. Neuropeptide W

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    Fumiko eTakenoya

    2012-12-01

    Full Text Available Neuropeptide W (NPW, which was first isolated from the porcine hypothalamus, exists in two forms, consisting of 23 (NPW23 or 30 (NPW30 amino acids. These neuropeptides bind to one of two neuropeptide W receptors, either NPBWR1 (otherwise known as GPR7 or NPBWR2 (GPR8, which belong to the G protein-coupled receptor family. GPR7 is expressed in the brain and peripheral organs of both humans and rodents, whereas GPR8 is not found in rodents. GPR7 mRNA in rodents is widely expressed in several hypothalamic regions, including the paraventricular, supraoptic, ventromedial, dorsomedial, suprachiasmatic and arcuate nuclei. These observations suggest that GPR7 plays a crucial role in the modulation of neuroendocrine function. The intracerebroventricular infusion of NPW has been shown to suppress food intake and body weight and to increase both heat production and body temperature, suggesting that this neuropeptide functions as an endogenous catabolic signaling molecule. Here we summarize our current understanding of the distribution and function of NPW in the brain.

  18. Neuropeptide processing in regional brain slices: Effect of conformation and sequence

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    Li, Z.W.; Bijl, W.A.; van Nispen, J.W.; Brendel, K.; Davis, T.P. (Univ. of Arizona, Tucson (USA))

    1990-05-01

    The central enzymatic stability of des-enkephalin-gamma-endorphin and its synthetic analogs (cycloN alpha 6, C delta 11)beta-endorphin-(6-17) and (Pro7, Lys(Ac)9)-beta-endorphin(6-17) was studied in vitro using a newly developed, regionally dissected rat brain slice, time course incubation procedure. Tissue slice viability was estimated as the ability of the brain slice to take up or release gamma-(3H)aminobutyric acid after high K+ stimulation. Results demonstrated stability of uptake/release up to 5 hr of incubation, suggesting tissue viability over this period. The estimated half-life of peptides based on the results obtained in our incubation protocol suggest that the peptides studied are metabolized at different rates in the individual brain regions tested. A good correlation exists between the high enzyme activity of neutral endopeptidase and the rapid degradation of des-enkephalin-gamma-endorphin and (cycloN alpha 6, C delata 11)beta-endorphin-(6-17) in caudate putamen. Proline substitution combined with lysine acetylation appears to improve resistance to enzymatic metabolism in caudate putamen and hypothalamus. However, cyclization of des-enkephalin-gamma-endorphin forming an amide bond between the alpha-NH2 of the N-terminal threonine and the gamma-COOH of glutamic acid did not improve peptide stability in any brain region tested. The present study has shown that the brain slice technique is a valid and unique approach to study neuropeptide metabolism in small, discrete regions of rat brain where peptides, peptidases and receptors are colocalized and that specific structural modifications can improve peptide stability.

  19. Long-term treatment with haloperidol affects neuropeptide S and NPSR mRNA levels in the rat brain.

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    Palasz, Artur; Rojczyk, Ewa; Golyszny, Milosz; Filipczyk, Lukasz; Worthington, John J; Wiaderkiewicz, Ryszard

    2016-04-01

    The brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression. We assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction. Chronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum. This stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.

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

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    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.

  1. Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder.

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    Tripp, Adam; Oh, Hyunjung; Guilloux, Jean-Philippe; Martinowich, Keri; Lewis, David A; Sibille, Etienne

    2012-11-01

    The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known. Using polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf(+/-)] mice and BDNF exon-IV knockout [Bdnf(KIV)] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results. Based on the results in Bdnf(+/-) and Bdnf(KIV) mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex. These parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis

  2. From motor cortex to visual cortex: the application of noninvasive brain stimulation to amblyopia.

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    Thompson, Benjamin; Mansouri, Behzad; Koski, Lisa; Hess, Robert F

    2012-04-01

    Noninvasive brain stimulation is a technique for inducing changes in the excitability of discrete neural populations in the human brain. A current model of the underlying pathological processes contributing to the loss of motor function after stroke has motivated a number of research groups to investigate the potential therapeutic application of brain stimulation to stroke rehabilitation. The loss of motor function is modeled as resulting from a combination of reduced excitability in the lesioned motor cortex and an increased inhibitory drive from the nonlesioned hemisphere over the lesioned hemisphere. This combination of impaired neural function and pathological suppression resonates with current views on the cause of the visual impairment in amblyopia. Here, we discuss how the rationale for using noninvasive brain stimulation in stroke rehabilitation can be applied to amblyopia, review a proof-of-principle study demonstrating that brain stimulation can temporarily improve amblyopic eye function, and propose future research avenues. Copyright © 2010 Wiley Periodicals, Inc.

  3. Interaction of neuropeptide Y genotype and childhood emotional maltreatment on brain activity during emotional processing

    NARCIS (Netherlands)

    Opmeer, E.M.; Kortekaas, R.; van Tol, M.J.; van der Wee, N.J.A.; Woudstra, S.; van Buchem, M.A.; Penninx, B.W.J.H.; Veltman, D.J.; Aleman, A.

    2014-01-01

    Neuropeptide Y (NPY) has been associated with stress reactivity in affective disorders and is most densely expressed in the amygdala. An important stressor associated with affective disorders is the experience of childhood emotional maltreatment (CEM). We investigated whether the interaction of NPY

  4. Interaction of neuropeptide Y genotype and childhood emotional maltreatment on brain activity during emotional processing

    NARCIS (Netherlands)

    Opmeer, Esther M.; Kortekaas, Rudie; van Tol, Marie-Jose; van der Wee, Nic J. A.; Woudstra, Saskia; van Buchem, Mark A.; Penninx, Brenda W. J. H.; Veltman, Dick J.; Aleman, Andre

    Neuropeptide Y (NPY) has been associated with stress reactivity in affective disorders and is most densely expressed in the amygdala. An important stressor associated with affective disorders is the experience of childhood emotional maltreatment (CEM). We investigated whether the interaction of NPY

  5. 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.

  6. Neuropeptide Y and Stress

    Directory of Open Access Journals (Sweden)

    Murat Gulsun

    2012-03-01

    Full Text Available The neurobiological aspects of stress and coping skills has been the focus of interest for many researchers. Some of the studies has shown that there is a significant relationship among genetically variables, stress response and life events. Neuropeptide Y is one of the systems regulating the stress response. Under the prolonged or repeated trauma neuropeptide Y is released from the brain's key areas. This system shows different levels of functioning in individuals with different levels of resilience. There is particular interest in the variations of genes that encode stress-sensitive signaling molecules during gene-environment interaction. This condition may contribute to susceptibility of stress or stress resilience. Neuropeptide Y system plays a key role in the adaptation to behavioral stress. The reduced levels of neuropeptide Y have also been observed in treatment-resistant depression and posttraumatic stress disorder. Lower level of neuropeptide Y expression and dysfunctional neuropeptide Y system in response to stress and resulting decreased stress resilience could increase susceptibility to stress-related disorders.

  7. Fetal frontal cortex transplant (14C) 2-deoxyglucose uptake and histology: survival in cavities of host rat brain motor cortex

    International Nuclear Information System (INIS)

    Sharp, F.R.; Gonzalez, M.F.

    1984-01-01

    Fetal frontal neocortex from 18-day-old rat embryonic brain was transplanted into cavities in 30-day-old host motor cortex. Sixty days after transplantation, 5 of 15 transplanted rats had surviving fetal transplants. The fetal cortex transplants were physically attached to the host brain, completely filled the original cavity, and had numerous surviving cells including pyramidal neurons. Cell lamination within the fetal transplant was abnormal. The ( 14 C) 2-deoxyglucose uptake of all five of the fetal neocortex transplants was less than adjacent cortex and contralateral host motor-sensory cortex, but more than adjacent corpus callosum white matter. The results indicate that fetal frontal neocortex can be transplanted into damaged rat motor cortex. The metabolic rate of the transplants suggests they could be partially functional

  8. An AAV promoter-driven neuropeptide Y gene delivery system using Sendai virosomes for neurons and rat brain.

    Science.gov (United States)

    Wu, P; de Fiebre, C M; Millard, W J; King, M A; Wang, S; Bryant, S O; Gao, Y P; Martin, E J; Meyer, E M

    1996-03-01

    An adeno-associated virus (AAV)-derived construct (pJDT95npy) containing rat neuropeptide Y (NPY) cDNA inserted downstream of endogenous AAV promoters was used to investigate AAV-driven NPY expression in postmitotic neurons in vitro and in the brain. NPY mRNA was expressed in NT2/N and rat brain primary neuronal cultures after transfection. There was a corresponding increase in the number of neurons staining for NPY-like immunoreactivity and an increase in NPY release during depolarization in the primary cultures. Injections of Sendai-virosome encapsulated pJDT95npy into neocortex increased NPY-like immunoreactivity in neurons but not glia indicating that the latter cell type did not have the translational, post-translational or storage capacity to accumulate the peptide. Injections into the rat hypothalamic para-ventricular nucleus increased body weight and food intake for 21 days, though NPY-like immunoreactivity remained elevated for at least 50 days. These studies demonstrate that AAV-derived constructs may be useful for delivering genes into post-mitotic neurons, and that Sendai virosomes are effective for delivering these constructs in vivo.

  9. Adrenergic receptors in frontal cortex in human brain.

    Science.gov (United States)

    Cash, R; Raisman, R; Ruberg, M; Agid, Y

    1985-02-05

    The binding of three adrenergic ligands ([3H]prazosin, [3H]clonidine, [3H]dihydroalprenolol) was studied in the frontal cortex of human brain. alpha 1-Receptors, labeled by [3H]prazosin, predominated. [3H]Clonidine bound to two classes of sites, one of high affinity and one of low affinity. Guanosine triphosphate appeared to lower the affinity of [3H]clonidine for its receptor. [3H]Dihydroalprenolol bound to three classes of sites: the beta 1-receptor, the beta 2-receptor and a receptor with low affinity which represented about 40% of the total binding, but which was probably a non-specific site; the beta 1/beta 2 ratio was 1/2.

  10. 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

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

    DEFF Research Database (Denmark)

    Liu, Xiaobin; Zeng, Joanne; Zhou, Anni

    2011-01-01

    /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...

  12. Identified peptidergic neurons in the Drosophila brain regulate insulin-producing cells, stress responses and metabolism by coexpressed short neuropeptide F and corazonin.

    Science.gov (United States)

    Kapan, Neval; Lushchak, Oleh V; Luo, Jiangnan; Nässel, Dick R

    2012-12-01

    Insulin/IGF-like signaling regulates the development, growth, fecundity, metabolic homeostasis, stress resistance and lifespan in worms, flies and mammals. Eight insulin-like peptides (DILP1-8) are found in Drosophila. Three of these (DILP2, 3 and 5) are produced by a set of median neurosecretory cells (insulin-producing cells, IPCs) in the brain. Activity in the IPCs of adult flies is regulated by glucose and several neurotransmitters and neuropeptides. One of these, short neuropeptide F (sNPF), regulates food intake, growth and Dilp transcript levels in IPCs via the sNPF receptor (sNPFR1) expressed on IPCs. Here we identify a set of brain neurons that utilizes sNPF to activate the IPCs. These sNPF-expressing neurons (dorsal lateral peptidergic neurons, DLPs) also produce the neuropeptide corazonin (CRZ) and have axon terminations impinging on IPCs. Knockdown of either sNPF or CRZ in DLPs extends survival in flies exposed to starvation and alters carbohydrate and lipid metabolism. Expression of sNPF in DLPs in the sNPF mutant background is sufficient to rescue wild-type metabolism and response to starvation. Since CRZ receptor RNAi in IPCs affects starvation resistance and metabolism, similar to peptide knockdown in DLPs, it is likely that also CRZ targets the IPCs. Knockdown of sNPF, but not CRZ in DLPs decreases transcription of Dilp2 and 5 in the brain, suggesting different mechanisms of action on IPCs of the two co-released peptides. Our findings indicate that sNPF and CRZ co-released from a small set of neurons regulate IPCs, stress resistance and metabolism in adult Drosophila.

  13. 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.

  14. 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

    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-...

  15. 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.

  16. Immunolocalization of the short neuropeptide F receptor in queen brains and ovaries of the red imported fire ant (Solenopsis invicta Buren

    Directory of Open Access Journals (Sweden)

    Pietrantonio Patricia V

    2011-06-01

    Full Text Available Abstract Background Insect neuropeptides are involved in diverse physiological functions and can be released as neurotransmitters or neuromodulators acting within the central nervous system, and as circulating neurohormones in insect hemolymph. The insect short neuropeptide F (sNPF peptides, related to the vertebrate neuropeptide Y (NPY peptides, have been implicated in the regulation of food intake and body size, and play a gonadotropic role in the ovaries of some insect species. Recently the sNPF peptides were localized in the brain of larval and adult Drosophila. However, the location of the sNPF receptor, a G protein-coupled receptor (GPCR, has not yet been investigated in brains of any adult insect. To elucidate the sites of action of the sNPF peptide(s, the sNPF receptor tissue expression and cellular localization were analyzed in queens of the red imported fire ant, Solenopsis invicta Buren (Hymenoptera, an invasive social insect. Results In the queen brains and subesophageal ganglion about 164 cells distributed in distinctive cell clusters (C1-C9 and C12 or as individual cells (C10, C11 were immuno-positive for the sNPF receptor. Most of these neurons are located in or near important sensory neuropils including the mushroom bodies, the antennal lobes, the central complex, and in different parts of the protocerebrum, as well as in the subesophageal ganglion. The localization of the sNPF receptor broadly links the receptor signaling pathway with circuits regulating learning and feeding behaviors. In ovaries from mated queens, the detection of sNPF receptor signal at the posterior end of oocytes in mid-oogenesis stage suggests that the sNPF signaling pathway may regulate processes at the oocyte pole. Conclusions The analysis of sNPF receptor immunolocalization shows that the sNPF signaling cascade may be involved in diverse functions, and the sNPF peptide(s may act in the brain as neurotransmitter(s or neuromodulator(s, and in the ovaries

  17. 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.

  18. Cloning, localization and differential expression of Neuropeptide-Y during early brain development and gonadal recrudescence in the catfish, Clarias gariepinus.

    Science.gov (United States)

    Sudhakumari, Cheni-Chery; Anitha, Arumugam; Murugananthkumar, Raju; Tiwari, Dinesh Kumar; Bhasker, Dharavath; Senthilkumaran, Balasubramanian; Dutta-Gupta, Aparna

    2017-09-15

    Neuropeptide-Y (NPY) has diverse physiological functions which are extensively studied in vertebrates. However, regulatory role of NPY in relation to brain ontogeny and recrudescence with reference to reproduction is less understood in fish. Present report for the first time evaluated the significance of NPY by transient esiRNA silencing and also analyzed its expression during brain development and gonadal recrudescence in the catfish, Clarias gariepinus. As a first step, full-length cDNA of NPY was cloned from adult catfish brain, which shared high homology with its counterparts from other teleosts upon phylogenetic analysis. Tissue distribution revealed dominant expression of NPY in brain and testis. NPY expression increased during brain development wherein the levels were higher in 100 and 150days post hatch females than the respective age-matched males. Seasonal cycle analysis showed high expression of NPY in brain during pre-spawning phase in comparison with other reproductive phases. Localization studies exhibited the presence of NPY, abundantly, in the regions of preoptic area, hypothalamus and pituitary. Transient silencing of NPY-esiRNA directly into the brain significantly decreased NPY expression in both the male and female brain of catfish which further resulted in significant decrease of transcripts of tryptophan hydroxylase 2, catfish gonadotropin-releasing hormone (cfGnRH), tyrosine hydroxylase and 3β-hydroxysteroid dehydrogenase in brain and luteinizing hormone-β/gonadotropin-II (lh-β/GTH-II) in pituitary exhibiting its influence on gonadal axis. In addition, significant decrease of several ovary-related transcripts was observed in NPY-esiRNA silenced female catfish, indicating the plausible role of NPY in ovary through cfGnRH-GTH axis. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 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.

  20. 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.

  1. Brain atrophy in the visual cortex and thalamus induced by severe stress in animal model.

    Science.gov (United States)

    Yoshii, Takanobu; Oishi, Naoya; Ikoma, Kazuya; Nishimura, Isao; Sakai, Yuki; Matsuda, Kenichi; Yamada, Shunji; Tanaka, Masaki; Kawata, Mitsuhiro; Narumoto, Jin; Fukui, Kenji

    2017-10-06

    Psychological stress induces many diseases including post-traumatic stress disorder (PTSD); however, the causal relationship between stress and brain atrophy has not been clarified. Applying single-prolonged stress (SPS) to explore the global effect of severe stress, we performed brain magnetic resonance imaging (MRI) acquisition and Voxel-based morphometry (VBM). Significant atrophy was detected in the bilateral thalamus and right visual cortex. Fluorescent immunohistochemistry for Iba-1 as the marker of activated microglia indicates regional microglial activation as stress-reaction in these atrophic areas. These data certify the impact of severe psychological stress on the atrophy of the visual cortex and the thalamus. Unexpectedly, these results are similar to chronic neuropathic pain rather than PTSD clinical research. We believe that some sensitisation mechanism from severe stress-induced atrophy in the visual cortex and thalamus, and the functional defect of the visual system may be a potential therapeutic target for stress-related diseases.

  2. 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

    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...

  3. Associative cortex features in the first olfactory brain relay station.

    Science.gov (United States)

    Doucette, Wilder; Gire, David H; Whitesell, Jennifer; Carmean, Vanessa; Lucero, Mary T; Restrepo, Diego

    2011-03-24

    Synchronized firing of mitral cells (MCs) in the olfactory bulb (OB) has been hypothesized to help bind information together in olfactory cortex (OC). In this survey of synchronized firing by suspected MCs in awake, behaving vertebrates, we find the surprising result that synchronized firing conveys information on odor value ("Is it rewarded?") rather than odor identity ("What is the odor?"). We observed that as mice learned to discriminate between odors, synchronous firing responses to the rewarded and unrewarded odors became divergent. Furthermore, adrenergic blockage decreases the magnitude of odor divergence of synchronous trains, suggesting that MCs contribute to decision-making through adrenergic-modulated synchronized firing. Thus, in the olfactory system information on stimulus reward is found in MCs one synapse away from the sensory neuron. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Changes of cerebral contents of neuropeptides in rat models of multiple ischemic dementia (MID)

    International Nuclear Information System (INIS)

    Zheng Xianghong; Guo Jingcai; Song Changyi; Wang Shejiao; Chen Wei

    2005-01-01

    Objective: To investigate the significance of changes of cerebral contents of the neuropeptides somatostatin (SS), arginine vasopressin (AVP) and substance P in rat models of MID. Methods: The rat models consisted of 15 rats undergoing intracarotid injection of autogenous thrombus powder. Another group of 15 rats undergoing sham operation served as controls. Learning and memory ability in these rats was assessed with daily passive avoidance task testing for 10 consecutive days. The animals were sacrificed on 30d and contents of the neuropeptides in tissue homogenate from different areas of brain (frontal cortex, temporal cortex, hippocampus, thalamus and corpus striatum) were measured with (RIA). Results: On the first day of passive avoidance task testing, the frequency of errors in the MID group and the control group was about the same. From the third day on, the frequency of errors in the MID group was significantly higher than that in the control group (P<0.05). The neuropeptides contents of all these cerebral areas in the MID group were significantly higher than those in the control group (P<0.05 or P<0.01) with the only exception of the contents of substance P in thalamus (no significant difference between the contents in the two groups). Conclusion: The impairment of learning and memory in rat models with MID was possibly related to the lowered contents of SS, AVP and substance P in the brain tissue. (authors)

  5. 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

  6. Semantic strategy training increases memory performance and brain activity in patients with prefrontal cortex lesions.

    Science.gov (United States)

    Miotto, Eliane C; Savage, Cary R; Evans, Jonathan J; Wilson, Barbara A; Martin, Maria G M; Balardin, Joana B; Barros, Fabio G; Garrido, Griselda; Teixeira, Manoel J; Amaro Junior, Edson

    2013-03-01

    Memory deficit is a frequent cognitive disorder following acquired prefrontal cortex lesions. In the present study, we investigated the brain correlates of a short semantic strategy training and memory performance of patients with distinct prefrontal cortex lesions using fMRI and cognitive tests. Twenty-one adult patients with post-acute prefrontal cortex (PFC) lesions, twelve with left dorsolateral PFC (LPFC) and nine with bilateral orbitofrontal cortex (BOFC) were assessed before and after a short cognitive semantic training using a verbal memory encoding paradigm during scanning and neuropsychological tests outside the scanner. After the semantic strategy training both groups of patients showed significant behavioral improvement in verbal memory recall and use of semantic strategies. In the LPFC group, greater activity in left inferior and medial frontal gyrus, precentral gyrus and insula was found after training. For the BOFC group, a greater activation was found in the left parietal cortex, right cingulated and precuneus after training. The activation of these specific areas in the memory and executive networks following cognitive training was associated to compensatory brain mechanisms and application of the semantic strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. 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...

  8. The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system.

    Science.gov (United States)

    Schéle, Erik; Grahnemo, Louise; Anesten, Fredrik; Hallén, Anna; Bäckhed, Fredrik; Jansson, John-Olov

    2013-10-01

    The gut microbiota contributes to fat mass and the susceptibility to obesity. However, the underlying mechanisms are not completely understood. To investigate whether the gut microbiota affects hypothalamic and brainstem body fat-regulating circuits, we compared gene expression of food intake-regulating neuropeptides between germ-free and conventionally raised (CONV-R) mice. We found that CONV-R mice had decreased expression of the antiobesity neuropeptide glucagon-like peptide-1 (GLP-1) precursor proglucagon (Gcg) in the brainstem. Moreover, in both the hypothalamus and the brainstem, CONV-R mice had decreased expression of the antiobesity neuropeptide brain-derived neurotrophic factor (Bdnf). CONV-R mice had reduced expression of the pro-obesity peptides neuropeptide-Y (Npy) and agouti-related protein (Agrp), and increased expression of the antiobesity peptides proopiomelanocortin (Pomc) and cocaine- and amphetamine-regulated transcript (Cart) in the hypothalamus. The latter changes in neuropeptide expression could be secondary to elevated fat mass in CONV-R mice. Leptin treatment caused less weight reduction and less suppression of orexigenic Npy and Agrp expression in CONV-R mice compared with germ-free mice. The hypothalamic expression of leptin resistance-associated suppressor of cytokine signaling 3 (Socs-3) was increased in CONV-R mice. In conclusion, the gut microbiota reduces the expression of 2 genes coding for body fat-suppressing neuropeptides, Gcg and Bdnf, an alteration that may contribute to fat mass induction by the gut microbiota. Moreover, the presence of body fat-inducing gut microbiota is associated with hypothalamic signs of Socs-3-mediated leptin resistance, which may be linked to failed compensatory body fat reduction.

  9. 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...

  10. Determination of hyperactive areas of Cortex Cerebri with using brain SPECT study

    International Nuclear Information System (INIS)

    Stepien, A.; Pawlus, J.; Wasilewska-Radwanska, M.

    2004-01-01

    The aim of this study was the assessment of the ability to apply of SPECT technique to determination of hyperactive areas of cortex cerebri. Analysis included 50 patients (mean aged 44 - 58). Brain SPECT scanning was performed after 1 hour after the intravenous injection of 740 MBq of ethylcisteinate dimmer labeled 99m Technetium (99mTc-ECD) with the use one-head gamma camera with a low-energy, ultra-high resolution collimator. Qualitative and quantitative analysis was performed using specialised software. In 20 cases normal biodistribution of the radiotracer was observed (hyperactive areas in cerebellum and occiput). In patients with psychiatric and neurological disturbances hyperactive areas were visualized in 25 cases in temporal lobes, in 4 cases in parietal lobes and in 1 patient in frontal area and basal ganglia. It is concluded that a number of factors limit the wide-scale use of SPECT, including the sophistication of imaging equipment (single-head cameras are inferior to the newer multihead units) and the experience of the physicians interpreting the scans and utilizing the data. In many diseases physicians do not know which areas of the patient's brain according disorders. Brain SPECT study can be a very useful tool to evaluation of hyperactive areas of cortex cerebri. This technique visualization of cortex cerebri completes standard analysis of disorders of brain activity

  11. 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. PMID:24416397

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

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    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.

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

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    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.

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

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    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.

  15. Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex.

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    Martín, Virginia; Fabelo, Noemí; Santpere, Gabriel; Puig, Berta; Marín, Raquel; Ferrer, Isidre; Díaz, Mario

    2010-01-01

    Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.

  16. Sendai virosomal infusion of an adeno-associated virus-derived construct containing neuropeptide Y into primary rat brain cultures.

    Science.gov (United States)

    Wu, P; de Fiebre, C M; Millard, W J; Elmstrom, K; Gao, Y; Meyer, E M

    1995-05-05

    A novel neuronal gene-delivery system was investigated in primary neuron-enriched cultures with respect to driving the expression of neuropeptide Y (NPY). This delivery system consists of an adeno-associated virus-derived (AAV) plasmid, pJDT95npy, encapsulated in reconstituted Sendai virosomes. pJDT95npy contains full length rat NPY cDNA inserted downstream from the P40 promoter in a cap-gene deleted AAV-derived construct. The rep-sequences under control of the P5 and P19 promoters are intact. Virosomally encapsulated pJDT95npy drove the expression of NPY mRNAs, predominantly by P40. Total cellular NPY immunoreactivity and release in the presence of depolarization increased following pJDT95npy-transfection. Neither empty virosomes nor virosomes containing pJDT95 affected NPY mRNA expression or immunoreactivity. This study demonstrates that an AAV-derived plasmid can drive exogenous gene expression in intact neurons after infusion by Sendai virosomes.

  17. Brain antibodies in the cortex and blood of people with schizophrenia and controls.

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    Glass, L J; Sinclair, D; Boerrigter, D; Naude, K; Fung, S J; Brown, D; Catts, V S; Tooney, P; O'Donnell, M; Lenroot, R; Galletly, C; Liu, D; Weickert, T W; Shannon Weickert, C

    2017-08-08

    The immune system is implicated in the pathogenesis of schizophrenia, with elevated proinflammatory cytokine mRNAs found in the brains of ~40% of individuals with the disorder. However, it is not clear if antibodies (specifically immunoglobulin-γ (IgG)) can be found in the brain of people with schizophrenia and if their abundance relates to brain inflammatory cytokine mRNA levels. Therefore, we investigated the localization and abundance of IgG in the frontal cortex of people with schizophrenia and controls, and the impact of proinflammatory cytokine status on IgG abundance in these groups. Brain IgGs were detected surrounding blood vessels in the human and non-human primate frontal cortex by immunohistochemistry. IgG levels did not differ significantly between schizophrenia cases and controls, or between schizophrenia cases in 'high' and 'low' proinflammatory cytokine subgroups. Consistent with the existence of IgG in the parenchyma of human brain, mRNA and protein of the IgG transporter (FcGRT) were present in the brain, and did not differ according to diagnosis or inflammatory status. Finally, brain-reactive antibody presence and abundance was investigated in the blood of living people. The plasma of living schizophrenia patients and healthy controls contained antibodies that displayed positive binding to Rhesus macaque cerebellar tissue, and the abundance of these antibodies was significantly lower in patients than controls. These findings suggest that antibodies in the brain and brain-reactive antibodies in the blood are present under normal circumstances.

  18. Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral Cortex Development.

    Science.gov (United States)

    Bárez-López, Soledad; Obregon, Maria Jesus; Bernal, Juan; Guadaño-Ferraz, Ana

    2018-05-01

    Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an essential role in neurodevelopment; however, the mechanisms underlying T3 brain delivery during mice fetal development are not well known. This work has explored the sources of brain T3 during mice fetal development using biochemical, anatomical, and molecular approaches. The findings revealed that during late gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the developing mouse brain, fetal T3 content is regulated through the conversion of T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier prenatal stages. Additionally, D2 activity was found to be essential to mediate expression of T3-dependent genes in the cerebral cortex, and also necessary to generate the transient cerebral cortex hyperthyroidism present in mice lacking the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB). Overall, these data signify that T4 deiodinated by D2 may be the only source of T3 during neocortical development. We therefore propose that D2 activity at the BCSFB converts the T4 transported across the choroid plexus into T3, thus supplying the brain with active hormone to maintain TH homeostasis.

  19. Laser technique for anatomical-functional study of the medial prefrontal cortex of the brain

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    Sanchez-Huerta, Laura; Hernandez, Adan; Ayala, Griselda; Marroquin, Javier; Silva, Adriana B.; Khotiaintsev, Konstantin S.; Svirid, Vladimir A.; Flores, Gonzalo; Khotiaintsev, Sergei N.

    1999-05-01

    The brain represents one of the most complex systems that we know yet. In its study, non-destructive methods -- in particular, behavioral studies play an important role. By alteration of brain functioning (e.g. by pharmacological means) and observation of consequent behavior changes an important information on brain organization and functioning is obtained. For inducing local alterations, permanent brain lesions are employed. However, for correct results this technique has to be quasi-non-destructive, i.e. not to affect the normal brain function. Hence, the lesions should be very small, accurate and applied precisely over the structure (e.g. the brain nucleus) of interest. These specifications are difficult to meet with the existing techniques for brain lesions -- specifically, neurotoxical, mechanical and electrical means because they result in too extensive damage. In this paper, we present new laser technique for quasi-non- destructive anatomical-functional mapping in vivo of the medial prefrontal cortex (MPFC) of the rat. The technique is based on producing of small-size, well-controlled laser- induced lesions over some areas of the MPFC. The anesthetized animals are subjected to stereotactic surgery and certain points of the MPFC are exposed the confined radiation of the 10 W cw CO2 laser. Subsequent behavioral changes observed in neonatal and adult animals as well as histological data prove effectiveness of this technology for anatomical- functional studies of the brain by areas, and as a treatment method for some pathologies.

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

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    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.

  1. 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

  2. Neuropeptides as mediators of the early-life impact on the brain; implications for alcohol use disorders

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    Ingrid eNylander

    2012-07-01

    Full Text Available The brain is constantly exposed to external and internal input and to function in an ever-changing environment we are dependent on processes that enable the brain to adapt to new stimuli. Exposure to postnatal environmental stimuli can interfere with vital adaption processes and cause long-term changes in physiological function and behaviour. Early-life alterations in brain function may result in impaired ability to adapt to new situations, in altered sensitivity to challenges later in life and thereby mediate risk or protection for psychopathology such as alcohol use disorders (AUD. In clinical research the studies of mechanisms, mediators and causal relation between early environmental factors and vulnerability to AUD are restricted and attempts are made to find valid animal models for studies of the early-life influence on the brain. This review focuses on rodent models and the effects of adverse and naturalistic conditions on peptide networks within the brain and pituitary gland. Importantly, the consequences of alcohol addiction are not discussed but rather neurobiological alterations that can cause risk consumption and vulnerability to addiction. The article reviews earlier results and includes new data with emphasis on endogenous opioid peptides but also oxytocin and vasopressin. These peptides are vital for developmental processes and it is hypothesized that early-life changes in peptide networks may interfere with neuronal processes and thereby contribute the individual vulnerability for AUD. The summarized results indicate a link between early-life rearing conditions, opioids and ethanol consumption and that the ethanol-induced effects and the treatment with opioid antagonists later in life are dependent on early-life experiences. Endogenous opioids are therefore of interest to further study in the early-life impact on individual differences in vulnerability to AUD and treatment outcome.

  3. Therapeutic deep brain stimulation in Parkinsonian rats directly influences motor cortex.

    Science.gov (United States)

    Li, Qian; Ke, Ya; Chan, Danny C W; Qian, Zhong-Ming; Yung, Ken K L; Ko, Ho; Arbuthnott, Gordon W; Yung, Wing-Ho

    2012-12-06

    Much recent discussion about the origin of Parkinsonian symptoms has centered around the idea that they arise with the increase of beta frequency waves in the EEG. This activity may be closely related to an oscillation between subthalamic nucleus (STN) and globus pallidus. Since STN is the target of deep brain stimulation, it had been assumed that its action is on the nucleus itself. By means of simultaneous recordings of the firing activities from populations of neurons and the local field potentials in the motor cortex of freely moving Parkinsonian rats, this study casts doubt on this assumption. Instead, we found evidence that the corrective action is upon the cortex, where stochastic antidromic spikes originating from the STN directly modify the firing probability of the corticofugal projection neurons, destroy the dominance of beta rhythm, and thus restore motor control to the subjects, be they patients or rodents. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Neuropathological Changes in Brain Cortex and Hippocampus in a Rat Model of Alzheimer’s Disease

    Science.gov (United States)

    Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Roosh, Nahid Rahbar; Omidzahir, Shila

    2011-01-01

    Background: Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Methods: Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and β-amyloid (Aβ) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 µL of Aβ (1-40) into the hippocampal fissure. Results: In the present study, Aβ (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. Aβ injection CA1 caused Aβ deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. Conclusion: We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group. PMID:21725500

  5. Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer's disease.

    Science.gov (United States)

    Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Rahbar Rooshandel, Nahid; Omidzahir, Shila

    2011-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and Beta amyloid (ABeta) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 muL of ABeta (1-40) into the hippocampal fissure. In the present study, ABeta (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. ABeta injection CA1 caused ABeta deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group.

  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

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    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.

  8. Motor areas of the frontal cortex in patients with motor eloquent brain lesions.

    Science.gov (United States)

    Bulubas, Lucia; Sabih, Jamil; Wohlschlaeger, Afra; Sollmann, Nico; Hauck, Theresa; Ille, Sebastian; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

    2016-12-01

    OBJECTIVE Because of its huge clinical potential, the importance of premotor areas for motor function itself and plastic reshaping due to tumors or ischemic brain lesions has received increased attention. Thus, in this study the authors used navigated transcranial magnetic stimulation (nTMS) to investigate whether tumorous brain lesions induce a change in motor cortex localization in the human brain. METHODS Between 2010 and 2013, nTMS motor mapping was performed in a prospective cohort of 100 patients with brain tumors in or adjacent to the rolandic cortex. Spatial data analysis was performed by normalization of the individual motor maps and creation of overlays according to tumor location. Analysis of motor evoked potential (MEP) latencies was performed regarding mean overall latencies and potentially polysynaptic latencies, defined as latencies longer than 1 SD above the mean value. Hemispheric dominance, lesion location, and motor-function deficits were also considered. RESULTS Graphical analysis showed that motor areas were not restricted to the precentral gyrus. Instead, they spread widely in the anterior-posterior direction. An analysis of MEP latency showed that mean MEP latencies were shortest in the precentral gyrus and longest in the superior and middle frontal gyri. The percentage of latencies longer than 1 SD differed widely across gyri. The dominant hemisphere showed a greater number of longer latencies than the nondominant hemisphere (p < 0.0001). Moreover, tumor location-dependent changes in distribution of polysynaptic latencies were observed (p = 0.0002). Motor-function deficit did not show any statistically significant effect. CONCLUSIONS The distribution of primary and polysynaptic motor areas changes in patients with brain tumors and highly depends on tumor location. Thus, these data should be considered for resection planning.

  9. Principles of Network Architecture Emerging from Comparisons of the Cerebral Cortex in Large and Small Brains.

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    Barbara L Finlay

    2016-09-01

    Full Text Available The cerebral cortex retains its fundamental organization, layering, and input-output relations as it scales in volume over many orders of magnitude in mammals. How is its network architecture affected by size scaling? By comparing network organization of the mouse and rhesus macaque cortical connectome derived from complete neuroanatomical tracing studies, a recent study in PLOS Biology shows that an exponential distance rule emerges that reveals the falloff in connection probability with distance in the two brains that in turn determines common organizational features.

  10. Role of brain-derived neurotrophic factor and nerve growth factor in the regulation of Neuropeptide W in vitro and in vivo.

    Science.gov (United States)

    Wang, Rikang; Yan, Fengxia; Liao, Rifang; Wan, Pei; Little, Peter J; Zheng, Wenhua

    2017-05-15

    Nerve growth factor (NGF) and Brain-derived neurotrophic factor (BDNF) are neurotrophic factors involved in the growth, survival and functioning of neurons. In addition, a possible role of neurotrophins, particularly BDNF, in HPA axis hyperactivation has recently been proposed. Neuropeptide W (NPW) is an endogenous peptide ligand for the GPR7 and GPR8 and a stress mediator in the hypothalamus. It activates the HPA axis by working on hypothalamic corticotrophin-releasing hormone (CRH). No information is available about the interrelationships between neurotrophines like NGF/BDNF and NPW. We studied the effect and underlying mechanisms of NGF/BDNF on the production of NPW in PC12 cells and hypothalamus. NGF time- and concentration-dependently stimulated the expression of NPW in PC12 cells. The effect of NGF was blocked by the inhibition of PI3K/Akt signal pathway with specific inhibitors for PI3K or AktsiRNA for Akt while inhibition of ERK pathway had no effect. Moreover, BDNF concentration-dependently induced the expression of NPW mRNA and decreased the expression of NPY mRNA in primary cultured hypothalamic neurons which was also blocked by a PI3K kinase inhibitor. Finally, in vivo study showed that exogenous BDNF injected icv increased NPW production in the hypothalamus and this effect was reversed by a PI3 kinase inhibitor. These results and the fact that BDNF was able to stimulate the expression of CRH demonstrated that neurotrophines can modulate the expression of NPW in neuronal cells via the PI3K/Akt pathway and suggest that BDNF might be involved in functions of the HPA axis, at least in part by modulating the expression of NPW/NPY and CRH. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Neuropeptides and seizures.

    Science.gov (United States)

    Snead, O C

    1986-11-01

    There are four lines of evidence for or against a role of neuropeptides in epilepsy: Administration of a variety of opiate agonists into the ventricles or brain of animals produces a constellation of electrical and behavioral changes, seemingly receptor-specific, both sensitive to the specific opiate antagonist naloxone as well as certain anticonvulsant drugs. The primary reservation concerning these data in terms of their relevance to epilepsy regards the fact that the peptides are exogenously administered in relatively high doses. Hence, these data may reflect neurotoxic effects of peptides rather than physiologic function. A variety of opiate agonists are anticonvulsant and naloxone shortens the postictal state in some experimental seizure models. One could attempt to reconcile these data with those in No. 1 by hypothesizing that the spikes and behavioral changes examined in the latter experimental parodynes represented a sort of isolated model of the postictal state. Naloxone has little effect in clinical epilepsy. These data are far from conclusive for two reasons. First, few patients have been studied. Second, because of the issue of opiate receptor heterogeneity and the high doses of naloxone needed experimentally to block non-mu opiate effects, the doses of naloxone used clinically to date are too low to rule out possible delta- or epsilon-mediated effects. The negative clinical data are illustrative of the dangers and difficulties of extrapolating data generated in animal models of seizures to the human condition. ACTH, a peptide that is derived from the same precursor molecule as beta-endorphin, is clearly an effective anticonvulsant in certain childhood seizure states. However, whether this is due to a direct or indirect (that is, cortisol) effect on brain is far from clear. Paradoxically, in contradistinction to other data concerning pro- and anticonvulsant properties of various opioid peptides, there is no animal model of infantile spasms to help

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

    OpenAIRE

    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 wer...

  13. Fluoxetine reverts chronic restraint stress-induced depression-like behaviour and increases neuropeptide Y and galanin expression in mice

    DEFF Research Database (Denmark)

    Christiansen, Søren Hofman Oliveira; Olesen, Mikkel Vestergaard; Wörtwein, Gitta

    2011-01-01

    Stressful life events and chronic stress are implicated in the development of depressive disorder in humans. Neuropeptide Y (NPY) and galanin have been shown to modulate the stress response, and exert antidepressant-like effects in rodents. To further investigate these neuropeptides in depression......-like behaviour, NPY and galanin gene expression was studied in brains of mice subjected to chronic restraint stress (CRS) and concomitant treatment with the antidepressant fluoxetine (FLX). CRS caused a significant increase in depression-like behaviour that was associated with increased NPY mRNA levels...... in the medial amygdala. Concomitant FLX treatment reverted depression-like effects of CRS and led to significant increases in levels of NPY and galanin mRNA in the dentate gyrus, amygdala, and piriform cortex. These findings suggest that effects on NPY and galanin gene expression could play a role...

  14. Non-invasive brain stimulation of motor cortex induces embodiment when integrated with virtual reality feedback.

    Science.gov (United States)

    Bassolino, M; Franza, M; Bello Ruiz, J; Pinardi, M; Schmidlin, T; Stephan, M A; Solcà, M; Serino, A; Blanke, O

    2018-04-01

    Previous evidence highlighted the multisensory-motor origin of embodiment - that is, the experience of having a body and of being in control of it - and the possibility of experimentally manipulating it. For instance, an illusory feeling of embodiment towards a fake hand can be triggered by providing synchronous visuo-tactile stimulation to the hand of participants and to a fake hand or by asking participants to move their hand and observe a fake hand moving accordingly (rubber hand illusion). Here, we tested whether it is possible to manipulate embodiment not through stimulation of the participant's hand, but by directly tapping into the brain's hand representation via non-invasive brain stimulation. To this aim, we combined transcranial magnetic stimulation (TMS), to activate the hand corticospinal representation, with virtual reality (VR), to provide matching (as contrasted to non-matching) visual feedback, mimicking involuntary hand movements evoked by TMS. We show that the illusory embodiment occurred when TMS pulses were temporally matched with VR feedback, but not when TMS was administered outside primary motor cortex, (over the vertex) or when stimulating motor cortex at a lower intensity (that did not activate peripheral muscles). Behavioural (questionnaires) and neurophysiological (motor-evoked-potentials, TMS-evoked-movements) measures further indicated that embodiment was not explained by stimulation per se, but depended on the temporal coherence between TMS-induced activation of hand corticospinal representation and the virtual bodily feedback. This reveals that non-invasive brain stimulation may replace the application of external tactile hand cues and motor components related to volition, planning and anticipation. © 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. 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

  16. The novel anticonvulsant neuropeptide and galanin analogue, NAX-5055, does not alter energy and amino acid metabolism in cultured brain cells

    DEFF Research Database (Denmark)

    Aldana, Blanca I; Waagepetersen, Helle S; Schousboe, Arne

    2017-01-01

    A large body of evidence suggests that the neuropeptide galanin plays an important role in seizure control. In line with this, it was demonstrated that the galanin analogue, NAX-5055, exerts a potent anticonvulsant activity in animal seizure models. We recently found that the NAX-5055-mediated an...

  17. Brain structural network topological alterations of the left prefrontal and limbic cortex in psychogenic erectile dysfunction.

    Science.gov (United States)

    Chen, Jianhuai; Chen, Yun; Gao, Qingqiang; Chen, Guotao; Dai, Yutian; Yao, Zhijian; Lu, Qing

    2018-05-01

    Despite increasing understanding of the cerebral functional changes and structural abnormalities in erectile dysfunction, alterations in the topological organization of brain networks underlying psychogenic erectile dysfunction remain unclear. Here, based on the diffusion tensor image data of 25 patients and 26 healthy controls, we investigated the topological organization of brain structural networks and its correlations with the clinical variables using the graph theoretical analysis. Patients displayed a preserved overall small-world organization and exhibited a less connectivity strength in the left inferior frontal gyrus, amygdale and the right inferior temporal gyrus. Moreover, an abnormal hub pattern was observed in patients, which might disturb the information interactions of the remaining brain network. Additionally, the clustering coefficient of the left hippocampus was positively correlated with the duration of patients and the normalized betweenness centrality of the right anterior cingulate gyrus and the left calcarine fissure were negatively correlated with the sum scores of the 17-item Hamilton Depression Rating Scale. These findings suggested that the damaged white matter and the abnormal hub distribution of the left prefrontal and limbic cortex might contribute to the pathogenesis of psychogenic erectile dysfunction and provided new insights into the understanding of the pathophysiological mechanisms of psychogenic erectile dysfunction.

  18. Synaptic proteome changes in the superior frontal gyrus and occipital cortex of the alcoholic brain.

    Science.gov (United States)

    Etheridge, Naomi; Lewohl, Joanne M; Mayfield, R Dayne; Harris, R Adron; Dodd, Peter R

    2009-06-24

    Cognitive deficits and behavioral changes that result from chronic alcohol abuse are a consequence of neuropathological changes which alter signal transmission through the neural network. To focus on the changes that occur at the point of connection between the neural network cells, synaptosomal preparations from post-mortem human brain of six chronic alcoholics and six non-alcoholic controls were compared using 2D-DIGE. Functionally affected and spared regions (superior frontal gyrus, SFG, and occipital cortex, OC, respectively) were analyzed from both groups to further investigate the specific pathological response that alcoholism has on the brain. Forty-nine proteins were differentially regulated between the SFG of alcoholics and the SFG of controls and 94 proteins were regulated in the OC with an overlap of 23 proteins. Additionally, the SFG was compared to the OC within each group (alcoholics or controls) to identify region specific differences. A selection were identified by MALDI-TOF mass spectrometry revealing proteins involved in vesicle transport, metabolism, folding and trafficking, and signal transduction, all of which have the potential to influence synaptic activity. A number of proteins identified in this study have been previously related to alcoholism; however, the focus on synaptic proteins has also uncovered novel alcoholism-affected proteins. Further exploration of these proteins will illuminate the mechanisms altering synaptic plasticity, and thus neuronal signaling and response, in the alcoholic brain.

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

    Science.gov (United States)

    Mokienko, Olesya A.; Chervyakov, Alexander V.; Kulikova, Sofia N.; Bobrov, Pavel D.; Chernikova, Liudmila A.; Frolov, Alexander A.; Piradov, Mikhail A.

    2013-01-01

    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. PMID:24319425

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Controlling absence seizures by deep brain stimulus applied on substantia nigra pars reticulata and cortex

    International Nuclear Information System (INIS)

    Hu, Bing; Wang, Qingyun

    2015-01-01

    Epilepsy is a typical neural disease in nervous system, and the control of seizures is very important for treating the epilepsy. It is well known that the drug treatment is the main strategy for controlling the epilepsy. However, there are about 10–15 percent of patients, whose seizures cannot be effectively controlled by means of the drug. Alternatively, the deep brain stimulus (DBS) technology is a feasible method to control the serious seizures. However, theoretical explorations of DBS are still absent, and need to be further made. Presently, we will explore to control the absence seizures by introducing the DBS to a basal ganglia thalamocortical network model. In particular, we apply DBS onto substantia nigra pars reticulata (SNr) and the cortex to explore its effects on controlling absence seizures, respectively. We can find that the absence seizure can be well controlled within suitable parameter ranges by tuning the period and duration of current stimulation as DBS is implemented in the SNr. And also, as the DBS is applied onto the cortex, it is shown that for the ranges of present parameters, only adjusting the duration of current stimulation is an effective control method for the absence seizures. The obtained results can have better understanding for the mechanism of DBS in the medical treatment.

  2. Brain cortex phosphatidylserine inhibits phosphatidylinositol turnover in rat anterior pituitary glands

    International Nuclear Information System (INIS)

    Bonetti, A.C.; Canonico, P.L.; MacLeod, R.M.

    1985-01-01

    The in vitro effect of bovine brain cortex phosphatidylserine on 32 Pi incorporation into phosphatidylinositol, phosphatidylcholine, and phosphatidylethanolamine of rat anterior pituitary glands was studied. Phosphatidylserine (0.1 to 66.6 microM) decreased the incorporation of 32 Pi into phosphatidylinositol, but not phosphatidylcholine or phosphatidylethanolamine, in a concentration-related manner. The inhibitory effect of phosphatidylinositol was similar to that of dopamine in the same experimental conditions. The combined effects of submaximal concentrations of dopamine and phosphatidylserine elicited an apparently additive inhibitory effect on phosphatidylinositol synthesis. The inhibitory effect of phosphatidylserine was completely reversed by haloperidol and sulpiride and only partially by pimozide, antidopaminergic agents which per se do not affect phosphatidylinositol synthesis. The stimulatory effect of TRH to increase 32 Pi incorporation into phosphatidylinositol was decreased by phosphatidylserine. These observations suggest that the decrease in prolactin release in the presence of phosphatidylserine may be evoked through a dopaminergic mechanism

  3. Neuropeptides in tendinopathy

    Science.gov (United States)

    Scott, Alexander; Bahr, Roald

    2014-01-01

    Tendinopathy is a clinical syndrome of pain, tendon thickening, and increased blood flow. The current review highlights evidence supporting an underlying role of neuropeptides in the etiology, clinical presentation, and treatment of painful overuse tendinopathy. Painful tendons demonstrate an increased presence of Substance P-containing nerves which are strongly implicated as a potential source of pain, but which also play important roles in the tendon’s attempt to self-repair. Recent findings have identified potential roles of additional sensory and autonomic neuropeptides which regulate pain, tissue remodeling, and vascular flow, including acetylcholine, noradrenaline and neuropeptide Y. Neuropeptide production within tendons is stimulated by mechanical load and exercise, and both direct and indirect neuropeptide effects may be responsible for the potential benefits of heavy-load eccentric loading. A model is presented which delineates the physiologic basis for signalling pathways between tenocytes, mast cells and sensory and autonomic nerves, with implications for understanding the mechanisms of traditional as well as emerging treatment strategies including sclerosing therapy and nitric oxide. PMID:19273194

  4. Protection of cortex by overlying meninges tissue during dynamic indentation of the adolescent brain.

    Science.gov (United States)

    MacManus, David B; Pierrat, Baptiste; Murphy, Jeremiah G; Gilchrist, Michael D

    2017-07-15

    Traumatic brain injury (TBI) has become a recent focus of biomedical research with a growing international effort targeting material characterization of brain tissue and simulations of trauma using computer models of the head and brain to try to elucidate the mechanisms and pathogenesis of TBI. The meninges, a collagenous protective tri-layer, which encloses the entire brain and spinal cord has been largely overlooked in these material characterization studies. This has resulted in a lack of accurate constitutive data for the cranial meninges, particularly under dynamic conditions such as those experienced during head impacts. The work presented here addresses this lack of data by providing for the first time, in situ large deformation material properties of the porcine dura-arachnoid mater composite under dynamic indentation. It is demonstrated that this tissue is substantially stiffer (shear modulus, μ=19.10±8.55kPa) and relaxes at a slower rate (τ 1 =0.034±0.008s, τ 2 =0.336±0.077s) than the underlying brain tissue (μ=6.97±2.26kPa, τ 1 =0.021±0.007s, τ 2 =0.199±0.036s), reducing the magnitudes of stress by 250% and 65% for strains that arise during indentation-type deformations in adolescent brains. We present the first mechanical analysis of the protective capacity of the cranial meninges using in situ micro-indentation techniques. Force-relaxation tests are performed on in situ meninges and cortex tissue, under large strain dynamic micro-indentation. A quasi-linear viscoelastic model is used subsequently, providing time-dependent mechanical properties of these neural tissues under loading conditions comparable to what is experienced in TBI. The reported data highlights the large differences in mechanical properties between these two tissues. Finite element simulations of the indentation experiments are also performed to investigate the protective capacity of the meninges. These simulations show that the meninges protect the underlying brain tissue

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

    Directory of Open Access Journals (Sweden)

    Laura V Cuaya

    Full Text Available 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.

  6. Acquired self-control of insula cortex modulates emotion recognition and brain network connectivity in schizophrenia.

    Science.gov (United States)

    Ruiz, Sergio; Lee, Sangkyun; Soekadar, Surjo R; Caria, Andrea; Veit, Ralf; Kircher, Tilo; Birbaumer, Niels; Sitaram, Ranganatha

    2013-01-01

    Real-time functional magnetic resonance imaging (rtfMRI) is a novel technique that has allowed subjects to achieve self-regulation of circumscribed brain regions. Despite its anticipated therapeutic benefits, there is no report on successful application of this technique in psychiatric populations. The objectives of the present study were to train schizophrenia patients to achieve volitional control of bilateral anterior insula cortex on multiple days, and to explore the effect of learned self-regulation on face emotion recognition (an extensively studied deficit in schizophrenia) and on brain network connectivity. Nine patients with schizophrenia were trained to regulate the hemodynamic response in bilateral anterior insula with contingent rtfMRI neurofeedback, through a 2-weeks training. At the end of the training stage, patients performed a face emotion recognition task to explore behavioral effects of learned self-regulation. A learning effect in self-regulation was found for bilateral anterior insula, which persisted through the training. Following successful self-regulation, patients recognized disgust faces more accurately and happy faces less accurately. Improvements in disgust recognition were correlated with levels of self-activation of right insula. RtfMRI training led to an increase in the number of the incoming and outgoing effective connections of the anterior insula. This study shows for the first time that patients with schizophrenia can learn volitional brain regulation by rtfMRI feedback training leading to changes in the perception of emotions and modulations of the brain network connectivity. These findings open the door for further studies of rtfMRI in severely ill psychiatric populations, and possible therapeutic applications. Copyright © 2011 Wiley Periodicals, Inc.

  7. Using Individualized Brain Network for Analyzing Structural Covariance of the Cerebral Cortex in Alzheimer's Patients.

    Science.gov (United States)

    Kim, Hee-Jong; Shin, Jeong-Hyeon; Han, Cheol E; Kim, Hee Jin; Na, Duk L; Seo, Sang Won; Seong, Joon-Kyung

    2016-01-01

    Cortical thinning patterns in Alzheimer's disease (AD) have been widely reported through conventional regional analysis. In addition, the coordinated variance of cortical thickness in different brain regions has been investigated both at the individual and group network levels. In this study, we aim to investigate network architectural characteristics of a structural covariance network (SCN) in AD, and further to show that the structural covariance connectivity becomes disorganized across the brain regions in AD, while the normal control (NC) subjects maintain more clustered and consistent coordination in cortical atrophy variations. We generated SCNs directly from T1-weighted MR images of individual patients using surface-based cortical thickness data, with structural connectivity defined as similarity in cortical thickness within different brain regions. Individual SCNs were constructed using morphometric data from the Samsung Medical Center (SMC) dataset. The structural covariance connectivity showed higher clustering than randomly generated networks, as well as similar minimum path lengths, indicating that the SCNs are "small world." There were significant difference between NC and AD group in characteristic path lengths (z = -2.97, p < 0.01) and small-worldness values (z = 4.05, p < 0.01). Clustering coefficients in AD was smaller than that of NC but there was no significant difference (z = 1.81, not significant). We further observed that the AD patients had significantly disrupted structural connectivity. We also show that the coordinated variance of cortical thickness is distributed more randomly from one region to other regions in AD patients when compared to NC subjects. Our proposed SCN may provide surface-based measures for understanding interaction between two brain regions with co-atrophy of the cerebral cortex due to normal aging or AD. We applied our method to the AD Neuroimaging Initiative (ADNI) data to show consistency in results with the SMC

  8. Effects of noise pollution stress during pregnancy on anatomical and functional brain cortex development of the offsprings of NMRI mice

    Directory of Open Access Journals (Sweden)

    Sara Bijani

    2012-12-01

    Full Text Available Introduction: Effects of stress on changes in neural system activity is well defined, which might be because of the changes in brain cortex architecture. In the present study, the effects of maternal noise stress on the morphological and functional changes in brain cortex of off springs of NMRI mice were examined.Materials and Methods: Female pregnant mice divided into two groups. Control group was maintained in their home cages without any invasion but the experimental group was exposed to the noise stress (80 db for 5 min/day from day zero of pregnancy to day 14 (i.e. 15 days. After delivery, six pups from each group were killed and their brains were fixed, sectioned and stained in H&E. These sections were investigated by MOTIC software for both control and experimental groups. Other pups were nursed by their mothers until their adolescence (22 g-8 weeks old. Then they were examined for behavioral side-biased and locomotor activity tests.Results: Decrease in cortex diameter and diameter of each layer for the experimental group was observed. In addition, neuron counting in each layer indicated that the number of the neurons in the middle and outer layers of cortex for the experimental group was reduced than the control group. In contrast, the number of the neurons in the inner layer of the experimental group was increased. From the functional view, in experimental group increases in left-handness especially in female off springs were observed. Furthermore, spontaneous locomotor activity in the new environment was increased in the experimental group.Conclusion: These results indicated that neuronal immigration and network connections in the inner layer of cortex through the middle and outer layers in the experimental group were inhibited. In other word, noise stress was able to inhibit brain cortex development in next generation

  9. [Advances in mass spectrometry-based approaches for neuropeptide analysis].

    Science.gov (United States)

    Ji, Qianyue; Ma, Min; Peng, Xin; Jia, Chenxi; Ji, Qianyue

    2017-07-25

    Neuropeptides are an important class of endogenous bioactive substances involved in the function of the nervous system, and connect the brain and other neural and peripheral organs. Mass spectrometry-based neuropeptidomics are designed to study neuropeptides in a large-scale manner and obtain important molecular information to further understand the mechanism of nervous system regulation and the pathogenesis of neurological diseases. This review summarizes the basic strategies for the study of neuropeptides using mass spectrometry, including sample preparation and processing, qualitative and quantitative methods, and mass spectrometry imagining.

  10. Immunochemical analysis of neuropeptides

    International Nuclear Information System (INIS)

    Rehfeld, J.F.; Hilsted, L.

    1987-01-01

    Measurement of neuropeptides requires assays that take into account the basic characteristics of bioactive peptides, i.e. the structural homology; the molecular heterogeneity of a given neuropeptide system; the widespread synthesis in different neurons and cells; and cell-specific processing of the primary translation product. Development of libraries of sensitive radioimmunoassays (RIAs), each of which is monospecific for essential sequences of propeptides, comply with some of the needs. Processing-site specific RIAs have proven particularly useful in combination with chromatography and enzymography. 4 references, 1 figure

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Cannabis use and brain structural alterations of the cingulate cortex in early psychosis.

    Science.gov (United States)

    Rapp, Charlotte; Walter, Anna; Studerus, Erich; Bugra, Hilal; Tamagni, Corinne; Röthlisberger, Michel; Borgwardt, Stefan; Aston, Jacqueline; Riecher-Rössler, Anita

    2013-11-30

    As cannabis use is more frequent in patients with psychosis than in the general population and is known to be a risk factor for psychosis, the question arises whether cannabis contributes to recently detected brain volume reductions in schizophrenic psychoses. This study is the first to investigate how cannabis use is related to the cingulum volume, a brain region involved in the pathogenesis of schizophrenia, in a sample of both at-risk mental state (ARMS) and first episode psychosis (FEP) subjects. A cross-sectional magnetic resonance imaging (MRI) study of manually traced cingulum in 23 FEP and 37 ARMS subjects was performed. Cannabis use was assessed with the Basel Interview for Psychosis. By using repeated measures analyses of covariance, we investigated whether current cannabis use is associated with the cingulum volume, correcting for age, gender, alcohol consumption, whole brain volume and antipsychotic medication. There was a significant three-way interaction between region (anterior/posterior cingulum), hemisphere (left/right cingulum) and cannabis use (yes/no). Post-hoc analyses revealed that this was due to a significant negative effect of cannabis use on the volume of the posterior cingulum which was independent of the hemisphere and diagnostic group and all other covariates we controlled for. In the anterior cingulum, we found a significant negative effect only for the left hemisphere, which was again independent of the diagnostic group. Overall, we found negative associations of current cannabis use with grey matter volume of the cingulate cortex, a region rich in cannabinoid CB1 receptors. As this finding has not been consistently found in healthy controls, it might suggest that both ARMS and FEP subjects are particularly sensitive to exogenous activation of these receptors. © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Brain networks of social action-outcome contingency: The role of the ventral striatum in integrating signals from the sensory cortex and medial prefrontal cortex.

    Science.gov (United States)

    Sumiya, Motofumi; Koike, Takahiko; Okazaki, Shuntaro; Kitada, Ryo; Sadato, Norihiro

    2017-10-01

    Social interactions can be facilitated by action-outcome contingency, in which self-actions result in relevant responses from others. Research has indicated that the striatal reward system plays a role in generating action-outcome contingency signals. However, the neural mechanisms wherein signals regarding self-action and others' responses are integrated to generate the contingency signal remain poorly understood. We conducted a functional MRI study to test the hypothesis that brain activity representing the self modulates connectivity between the striatal reward system and sensory regions involved in the processing of others' responses. We employed a contingency task in which participants made the listener laugh by telling jokes. Participants reported more pleasure when greater laughter followed their own jokes than those of another. Self-relevant listener's responses produced stronger activation in the medial prefrontal cortex (mPFC). Laughter was associated with activity in the auditory cortex. The ventral striatum exhibited stronger activation when participants made listeners laugh than when another did. In physio-physiological interaction analyses, the ventral striatum showed interaction effects for signals extracted from the mPFC and auditory cortex. These results support the hypothesis that the mPFC, which is implicated in self-related processing, gates sensory input associated with others' responses during value processing in the ventral striatum. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. 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

  15. Functional Magnetic Resonance Imaging of Rats with Experimental Autoimmune Encephalomyelitis Reveals Brain Cortex Remodeling

    Science.gov (United States)

    Tambalo, Stefano; Peruzzotti-Jametti, Luca; Rigolio, Roberta; Fiorini, Silvia; Bontempi, Pietro; Mallucci, Giulia; Balzarotti, Beatrice; Marmiroli, Paola; Sbarbati, Andrea; Cavaletti, Guido

    2015-01-01

    Cortical reorganization occurring in multiple sclerosis (MS) patients is thought to play a key role in limiting the effect of structural tissue damage. Conversely, its exhaustion may contribute to the irreversible disability that accumulates with disease progression. Several aspects of MS-related cortical reorganization, including the overall functional effect and likely modulation by therapies, still remain to be elucidated. The aim of this work was to assess the extent of functional cortical reorganization and its brain structural/pathological correlates in Dark Agouti rats with experimental autoimmune encephalomyelitis (EAE), a widely accepted preclinical model of chronic MS. Morphological and functional MRI (fMRI) were performed before disease induction and during the relapsing and chronic phases of EAE. During somatosensory stimulation of the right forepaw, fMRI demonstrated that cortical reorganization occurs in both relapsing and chronic phases of EAE with increased activated volume and decreased laterality index versus baseline values. Voxel-based morphometry demonstrated gray matter (GM) atrophy in the cerebral cortex, and both GM and white matter atrophy were assessed by ex vivo pathology of the sensorimotor cortex and corpus callosum. Neuroinflammation persisted in the relapsing and chronic phases, with dendritic spine density in the layer IV sensory neurons inversely correlating with the number of cluster of differentiation 45-positive inflammatory lesions. Our work provides an innovative experimental platform that may be pivotal for the comprehension of key mechanisms responsible for the accumulation of irreversible brain damage and for the development of innovative therapies to reduce disability in EAE/MS. SIGNIFICANCE STATEMENT Since the early 2000s, functional MRI (fMRI) has demonstrated profound modifications in the recruitment of cortical areas during motor, cognitive, and sensory tasks in multiple sclerosis (MS) patients. Experimental autoimmune

  16. 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

  17. 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...

  18. Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer's Disease Entorhinal Cortex.

    Science.gov (United States)

    Murray, Helen C; Swanson, Molly E V; Dieriks, B Victor; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

    2018-02-21

    Polysialylated neural cell adhesion molecule (PSA-NCAM) is widely expressed in the adult human brain and facilitates structural remodeling of cells through steric inhibition of intercellular NCAM adhesion. We previously showed that PSA-NCAM immunoreactivity is decreased in the entorhinal cortex in Alzheimer's disease (AD). Based on available evidence, we hypothesized that a loss of PSA-NCAM + interneurons may underlie this reduction. PSA-NCAM expression by interneurons has previously been described in the human medial prefrontal cortex. Here we used postmortem human brain tissue to provide further evidence of PSA-NCAM + interneurons throughout the human hippocampal formation and additional cortical regions. Furthermore, PSA-NCAM + cell populations were assessed in the entorhinal cortex of normal and AD cases using fluorescent double labeling and manual cell counting. We found a significant decrease in the number of PSA-NCAM + cells per mm 2 in layer II and V of the entorhinal cortex, supporting our previous description of reduced PSA-NCAM immunoreactivity. Additionally, we found a significant decrease in the proportion of PSA-NCAM + cells that co-labeled with NeuN and parvalbumin, but no change in the proportion that co-labeled with calbindin or calretinin. These results demonstrate that PSA-NCAM is expressed by a variety of interneuron populations throughout the brain. Furthermore, that loss of PSA-NCAM expression by NeuN + cells predominantly contributes to the reduced PSA-NCAM immunoreactivity in the AD entorhinal cortex. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Histochemical changes of capillaries in rat brain cortex after irradiation with supralethal doses of gamma radiation

    International Nuclear Information System (INIS)

    Kamarad, V.; Dosoudilova, M.

    1987-01-01

    Changes were studied in the activities of alkaline phosphatase, ATP-splitting enzyme, thiaminepyrophosphatase, acetylcholinesterase, and of butyrylcholinesterase in the capillary sheet of the rat brain cortex of the laterobasal section of a parietal lobe following irradiation with 150 and 300 Gy. The animals were exposed to local irradiation of the head with gamma radiation using 60 Co at a dose rate of 6.9 Gy per min. The material was removed at the intervals of 30 and 60 mins after irradiation. All the studied enzymes, except the ATP-splitting enzyme, showed identical reaction to irradiation. At both intervals, the reaction after irradiation with 300 Gy was lower when compared to that after irradiation with 150 Gy. 30 mins after irradiation with 150 Gy an increased enzyme activity was shown followed by a marked decrease in the activity 60 mins after irradiation, compared with findings obtained from control animals. No similar time dependence was observed after irradiation with 300 Gy. The ATP-splitting enzyme showed a significant decrease in the activity 30 mins after irradiation with 150 Gy. On the other hand, 60 mins after irradiation with 150 Gy and at both time intervals after irradiation with 300 Gy, the activity was higher than that in control animals. (author). 6 figs., 14 refs

  20. Oxytocin: the neuropeptide of love reveals some of its secrets.

    Science.gov (United States)

    Neumann, Inga D

    2007-04-01

    The neuropeptide oxytocin is synthesized in the brain and released from neurohypophyseal terminals into the blood and within defined brain regions that regulate emotional, cognitive, and social behaviors. A recent study of CD38-/- mice (Jin et al., 2007) has demonstrated an essential role for the transmembrane receptor CD38 in secretion of oxytocin into the blood.

  1. Functional MR imaging of the motor cortex in healthy volunteers and patients with brain tumours: qualitative and quantitative results

    International Nuclear Information System (INIS)

    Fellner, C.; Friedrich-Alexander-Univ., Erlangen-Nuernberg; Schlaier, J.; Schwerdtner, J.; Brawanski, A.; Fellner, F.; Oberoesterreichische Landesnervenklinik, Linz; Held, P.; Blank, M.; Kalender, W.A.

    1999-01-01

    The purpose of this study was to compare functional magnetic resonance (MR) imaging of the motor cortex in healthy volunteers and patients with brain tumours. Functional MR imaging was performed in 14 healthy volunteers and 14 patients with tumours in or near the primary motor cortex with groups being matched for age, sex, and handedness. Functional images were acquired during motion of the right and left hand. Time courses of signal intensity within the contralateral, ipsilateral, and supplementary motor cortex as well as z-maps were calculated, their quality being assessed visually. Mean signal increase between activation and rest were evaluated within the contralateral, ipsilateral, and supplementary motor cortex, the activated area in those regions of interest was measured using z-maps. The quality of functional MR experiments was generally lower in patients than in volunteers. The quantitative results showed a trend towards increased ipsilateral activation in volunteers during left hand compared to right hand motion and in patients during motion of the affected compared to the non-affected hand. Considering quantitative and qualitative results, significantly increased ipsilateral activation was found in patients compared to healthy volunteers. In conclusion, functional MR imaging quality was significantly reduced in patient studies compared to healthy volunteers, even if influences of age, sex, and handedness were excluded. Increased ipsilateral activation was found in patients with brain tumours which can be interpreted by an improved connectivity between both hemispheres. (orig.) [de

  2. 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.

    2016-01-01

    In this section 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 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 various other neuro-peptides, -transmitters, -modulators and –hormones, 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. PMID:22249811

  3. Brain cortex muscarinic transmission is impaired in young adult transgenic Appswe/Ps1de9 female mice

    Czech Academy of Sciences Publication Activity Database

    Machová, Eva; Jakubík, Jan; Michal, Pavel; Oksman, M.; Iivonen, H.; Tanila, H.; Doležal, Vladimír

    2007-01-01

    Roč. 4, Suppl.1 (2007), s. 281-281 ISSN 1660-2854. [International conference Alzheimer ´s diseases/Parkinson´s diseases /8./. 14.03.2007-18.03.2007, Salzburg] R&D Projects: GA AV ČR(CZ) IAA5011206; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpr1 * brain cortex * muscarinic transmission * Alzheimer ´s disease Subject RIV: FH - Neurology

  4. Three-dimensional visualization of functional brain tissue and functional magnetic resonance imaging-integrated neuronavigation in the resection of brain tumor adjacent to motor cortex

    International Nuclear Information System (INIS)

    Han Tong; Cui Shimin; Tong Xiaoguang; Liu Li; Xue Kai; Liu Meili; Liang Siquan; Zhang Yunting; Zhi Dashi

    2011-01-01

    Objective: To assess the value of three -dimensional visualization of functional brain tissue and the functional magnetic resonance imaging (fMRI)-integrated neuronavigation in the resection of brain tumor adjacent to motor cortex. Method: Sixty patients with tumor located in the central sulcus were enrolled. Thirty patients were randomly assigned to function group and 30 to control group. Patients in function group underwent fMRI to localize the functional brain tissues. Then the function information was transferred to the neurosurgical navigator. The patients in control group underwent surgery with navigation without function information. The therapeutic effect, excision rate. improvement of motor function, and survival quality during follow-up were analyzed. Result: All patients in function group were accomplished visualization of functional brain tissues and fMRI-integrated neuronavigation. The locations of tumors, central sulcus and motor cortex were marked during the operation. The fMRI -integrated information played a great role in both pre- and post-operation. Pre-operation: designing the location of the skin flap and window bone, determining the relationship between the tumor and motor cortex, and designing the pathway for the resection. Post- operation: real-time navigation of relationship between the tumor and motor cortex, assisting to localize the motor cortex using interoperation ultra-sound for correcting the displacement by the CSF outflow and collapsing tumor. The patients in the function group had better results than the patients in the control group in therapeutic effect (u=2.646, P=0.008), excision rate (χ = 7.200, P<0.01), improvement of motor function (u=2.231, P=0.026), and survival quality (KPS u c = 2.664, P=0.008; Zubrod -ECOG -WHO u c =2.135, P=0.033). Conclusions: Using preoperative three -dimensional visualization of cerebral function tissue and the fMRI-integrated neuronavigation technology, combining intraoperative accurate

  5. Non-stationary discharge patterns in motor cortex under subthalamic nucleus deep brain stimulation.

    Science.gov (United States)

    Santaniello, Sabato; Montgomery, Erwin B; Gale, John T; Sarma, Sridevi V

    2012-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) directly modulates the basal ganglia (BG), but how such stimulation impacts the cortex upstream is largely unknown. There is evidence of cortical activation in 6-hydroxydopamine (OHDA)-lesioned rodents and facilitation of motor evoked potentials in Parkinson's disease (PD) patients, but the impact of the DBS settings on the cortical activity in normal vs. Parkinsonian conditions is still debated. We use point process models to analyze non-stationary activation patterns and inter-neuronal dependencies in the motor and sensory cortices of two non-human primates during STN DBS. These features are enhanced after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes a consistent PD-like motor impairment, while high-frequency (HF) DBS (i.e., ≥100 Hz) strongly reduces the short-term patterns (period: 3-7 ms) both before and after MPTP treatment, and elicits a short-latency post-stimulus activation. Low-frequency DBS (i.e., ≤50 Hz), instead, has negligible effects on the non-stationary features. Finally, by using tools from the information theory [i.e., receiver operating characteristic (ROC) curve and information rate (IR)], we show that the predictive power of these models is dependent on the DBS settings, i.e., the probability of spiking of the cortical neurons (which is captured by the point process models) is significantly conditioned on the timely delivery of the DBS input. This dependency increases with the DBS frequency and is significantly larger for high- vs. low-frequency DBS. Overall, the selective suppression of non-stationary features and the increased modulation of the spike probability suggest that HF STN DBS enhances the neuronal activation in motor and sensory cortices, presumably because of reinforcement mechanisms, which perhaps involve the overlap between feedback antidromic and feed-forward orthodromic responses along the BG-thalamo-cortical loop.

  6. Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder.

    Science.gov (United States)

    Ajram, L A; Horder, J; Mendez, M A; Galanopoulos, A; Brennan, L P; Wichers, R H; Robertson, D M; Murphy, C M; Zinkstok, J; Ivin, G; Heasman, M; Meek, D; Tricklebank, M D; Barker, G J; Lythgoe, D J; Edden, R A E; Williams, S C; Murphy, D G M; McAlonan, G M

    2017-05-23

    Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the 'responsivity' of the E-I system to pharmacologic challenge; or whether E-I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder. Therefore, we used magnetic resonance spectroscopy ([1H]MRS) to measure prefrontal E-I flux in response to the glutamate and GABA acting drug riluzole in adult men with and without ASD. We compared the change in prefrontal 'Inhibitory Index'-the GABA fraction within the pool of glutamate plus GABA metabolites-post riluzole challenge; and the impact of riluzole on differences in resting-state functional connectivity. Despite no baseline differences in E-I balance, there was a significant group difference in response to pharmacologic challenge. Riluzole increased the prefrontal cortex inhibitory index in ASD but decreased it in controls. There was also a significant group difference in prefrontal functional connectivity at baseline, which was abolished by riluzole within the ASD group. Our results also show, for we believe the first time in ASD, that E-I flux can be 'shifted' with a pharmacologic challenge, but that responsivity is significantly different from controls. Further, our initial evidence suggests that abnormalities in functional connectivity can be 'normalised' by targeting E-I, even in adults.

  7. 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.

  8. Stereotactically-guided Ablation of the Rat Auditory Cortex, and Localization of the Lesion in the Brain.

    Science.gov (United States)

    Lamas, Verónica; Estévez, Sheila; Pernía, Marianni; Plaza, Ignacio; Merchán, Miguel A

    2017-10-11

    The rat auditory cortex (AC) is becoming popular among auditory neuroscience investigators who are interested in experience-dependence plasticity, auditory perceptual processes, and cortical control of sound processing in the subcortical auditory nuclei. To address new challenges, a procedure to accurately locate and surgically expose the auditory cortex would expedite this research effort. Stereotactic neurosurgery is routinely used in pre-clinical research in animal models to engraft a needle or electrode at a pre-defined location within the auditory cortex. In the following protocol, we use stereotactic methods in a novel way. We identify four coordinate points over the surface of the temporal bone of the rat to define a window that, once opened, accurately exposes both the primary (A1) and secondary (Dorsal and Ventral) cortices of the AC. Using this method, we then perform a surgical ablation of the AC. After such a manipulation is performed, it is necessary to assess the localization, size, and extension of the lesions made in the cortex. Thus, we also describe a method to easily locate the AC ablation postmortem using a coordinate map constructed by transferring the cytoarchitectural limits of the AC to the surface of the brain.The combination of the stereotactically-guided location and ablation of the AC with the localization of the injured area in a coordinate map postmortem facilitates the validation of information obtained from the animal, and leads to a better analysis and comprehension of the data.

  9. Top-down modulation in the infant brain: Learning-induced expectations rapidly affect the sensory cortex at 6 months.

    Science.gov (United States)

    Emberson, Lauren L; Richards, John E; Aslin, Richard N

    2015-08-04

    Recent theoretical work emphasizes the role of expectation in neural processing, shifting the focus from feed-forward cortical hierarchies to models that include extensive feedback (e.g., predictive coding). Empirical support for expectation-related feedback is compelling but restricted to adult humans and nonhuman animals. Given the considerable differences in neural organization, connectivity, and efficiency between infant and adult brains, it is a crucial yet open question whether expectation-related feedback is an inherent property of the cortex (i.e., operational early in development) or whether expectation-related feedback develops with extensive experience and neural maturation. To determine whether infants' expectations about future sensory input modulate their sensory cortices without the confounds of stimulus novelty or repetition suppression, we used a cross-modal (audiovisual) omission paradigm and used functional near-infrared spectroscopy (fNIRS) to record hemodynamic responses in the infant cortex. We show that the occipital cortex of 6-month-old infants exhibits the signature of expectation-based feedback. Crucially, we found that this region does not respond to auditory stimuli if they are not predictive of a visual event. Overall, these findings suggest that the young infant's brain is already capable of some rudimentary form of expectation-based feedback.

  10. 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...... the medial and rostral pole of the frontal lobe as well as the anterior cingulate, anterior insular and dorsomedial frontal cortices. Subsequently, the reciprocity and specificity of these connections were tested from injections into the traced frontal cortices indicating that the PFC has cortical...... 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...

  11. 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.

  12. Overall biological activity of sensorimotor and visual brain cortex of rabbits with early neurological disorders induced by high doses of γ-radiation

    International Nuclear Information System (INIS)

    Silin, D.Ya.

    1988-01-01

    The overall bioelectrical activity of the sensorimotor and visual brain cortex of rabbits was estimated during early neurological impairment caused by 120 Gy gamma irradiation. The characteristic changes were revealed in the amplitude, form, energy spectrum and spatial biopotential synchronization. The changes in the bioelectrical activity of the brain were associated with the clinically displayed stages of the neurological process development

  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. Brain activation during fast driving in a driving simulator: the role of the lateral prefrontal cortex.

    Science.gov (United States)

    Jäncke, Lutz; Brunner, Béatrice; Esslen, Michaela

    2008-07-16

    Little is currently known about the neural underpinnings of the cognitive control of driving behavior in realistic situations and of the driver's speeding behavior in particular. In this study, participants drove in realistic scenarios presented in a high-end driving simulator. Scalp-recorded EEG oscillations in the alpha-band (8-13 Hz) with a 30-electrode montage were recorded while the participants drove under different conditions: (i) excessively fast (Fast), (ii) in a controlled manner at a safe speed (Correct), and (iii) impatiently in the context of testing traffic conditions (Impatient). Intracerebral sources of alpha-band activation were estimated using low resolution electrical tomography. Given that previous studies have shown a strong negative correlation between the Bold response in the frontal cortex and the alpha-band power, we used alpha-band-related activity as an estimation of frontal activation. Statistical analysis revealed more alpha-band-related activity (i.e. less neuronal activation) in the right lateral prefrontal cortex, including the dorsolateral prefrontal cortex, during fast driving. Those participants who speeded most and exhibited greater risk-taking behavior demonstrated stronger alpha-related activity (i.e. less neuronal activation) in the left anterior lateral prefrontal cortex. These findings are discussed in the context of current theories about the role of the lateral prefrontal cortex in controlling risk-taking behavior, task switching, and multitasking.

  15. 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

    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

  16. Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex.

    Science.gov (United States)

    Kutsuna, Nobuo; Yamashita, Akiko; Eriguchi, Takashi; Oshima, Hideki; Suma, Takeshi; Sakatani, Kaoru; Yamamoto, Takamitsu; Yoshino, Atsuo; Katayama, Yoichi

    2014-01-01

    Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  17. The Cortical Connectivity of the Prefrontal Cortex in the Monkey Brain

    Science.gov (United States)

    Yeterian, Edward H.; Pandya, Deepak N.; Tomaiuolo, Francesco; Petrides, Michael

    2011-01-01

    One dimension of understanding the functions of the prefrontal cortex is knowledge of cortical connectivity. We have surveyed three aspects of prefrontal cortical connections: local projections (within the frontal lobe), the termination patterns of long association (post-Rolandic) projections, and the trajectories of major fiber pathways. The local connections appear to be organized in relation to dorsal (hippocampal origin) and ventral (paleocortical origin) architectonic trends. According to the proposal of a dual origin of the cerebral cortex, cortical areas can be traced as originating from archicortex (hippocampus) on the one hand, and paleocortex, on the other hand, in a stepwise manner (e.g., Sanides, 1969; Pandya and Yeterian, 1985). Prefrontal areas within each trend are connected with less architectonically differentiated areas, and, on the other hand, with more differentiated areas. Such organization may allow for the systematic exchange of information within each architectonic trend. The long connections of the prefrontal cortex with post-Rolandic regions seem to be organized preferentially in relation to dorsal and ventral prefrontal architectonic trends. Prefrontal areas are connected with post-Rolandic auditory, visual and somatosensory association areas, and with multimodal and paralimbic regions. This long connectivity likely works in conjunction with local connections to serve prefrontal cortical functions. The afferent and efferent connections of the prefrontal cortex with post-Rolandic regions are conveyed by specific long association pathways. These pathways as well appear to be organized in relation to dorsal and ventral prefrontal architectonic trends. Finally, although prefrontal areas have preferential connections in relation to dual architectonic trends, it is clear that there are interconnections between and among areas in each trend, which may provide a substrate for the overall integrative function of the prefrontal cortex. Prefrontal

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

    Science.gov (United States)

    Primiani, Christopher T; Ryan, Veronica H; Rao, Jagadeesh S; Cam, Margaret C; Ahn, Kwangmi; Modi, Hiren R; Rapoport, Stanley I

    2014-01-01

    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. 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. 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. 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. 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 changes. Thus, comparable transcriptional regulatory networks that operate

  19. 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 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.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.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.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.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 changes. Thus, comparable transcriptional regulatory networks

  20. Coordinated Gene Expression of Neuroinflammatory and Cell Signaling Markers in Dorsolateral Prefrontal Cortex during Human Brain Development and Aging

    Science.gov (United States)

    Primiani, Christopher T.; Ryan, Veronica H.; Rao, Jagadeesh S.; Cam, Margaret C.; Ahn, Kwangmi; Modi, Hiren R.; Rapoport, Stanley I.

    2014-01-01

    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 changes. Thus, comparable

  1. 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.

  2. How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

    Science.gov (United States)

    Lang, Nicolas; Siebner, Hartwig R; Ward, Nick S; Lee, Lucy; Nitsche, Michael A; Paulus, Walter; Rothwell, John C; Lemon, Roger N; Frackowiak, Richard S

    2005-07-01

    Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.

  3. 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…

  4. 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…

  5. 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

  6. 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.

  7. Diabetic brain or retina? Visual psychophysical performance in diabetic patients in relation to GABA levels in occipital cortex.

    Science.gov (United States)

    Sanches, Mafalda; Abuhaiba, Sulaiman I; d'Almeida, Otília C; Quendera, Bruno; Gomes, Leonor; Moreno, Carolina; Guelho, Daniela; Castelo-Branco, Miguel

    2017-06-01

    Visual impairment is one of the most feared complications of Type 2 Diabetes Mellitus. Here, we aimed to investigate the role of occipital cortex γ-aminobutyric acid (GABA) as a predictor of visual performance in type 2 diabetes. 18 type 2 diabetes patients were included in a longitudinal prospective one-year study, as well as 22 healthy age-matched controls. We collected demographic data, HbA1C and used a novel set of visual psychophysical tests addressing color, achromatic luminance and speed discrimination in both groups. Psychophysical tests underwent dimension reduction with principle component analysis into three synthetic variables: speed, achromatic luminance and color discrimination. A MEGA-PRESS magnetic resonance brain spectroscopy sequence was used to measure occipital GABA levels in the type 2 diabetes group. Retinopathy grading and retinal microaneurysms counting were performed in the type 2 diabetes group for single-armed correlations. Speed discrimination thresholds were significantly higher in the type 2 diabetes group in both visits; mean difference (95% confidence interval), [0.86 (0.32-1.40) in the first visit, 0.74 (0.04-1.44) in the second visit]. GABA from the occipital cortex predicted speed and achromatic luminance discrimination thresholds within the same visit (r = 0.54 and 0.52; p = 0.02 and 0.03, respectively) in type 2 diabetes group. GABA from the occipital cortex also predicted speed discrimination thresholds one year later (r = 0.52; p = 0.03) in the type 2 diabetes group. Our results suggest that speed discrimination is impaired in type 2 diabetes and that occipital cortical GABA is a novel predictor of visual psychophysical performance independently from retinopathy grade, metabolic control or disease duration in the early stages of the disease.

  8. Brain Damage and Motor Cortex Impairment in Chronic Obstructive Pulmonary Disease: Implication of Nonrapid Eye Movement Sleep Desaturation.

    Science.gov (United States)

    Alexandre, Francois; Heraud, Nelly; Sanchez, Anthony M J; Tremey, Emilie; Oliver, Nicolas; Guerin, Philippe; Varray, Alain

    2016-02-01

    Nonrapid eye movement (NREM) sleep desaturation may cause neuronal damage due to the withdrawal of cerebrovascular reactivity. The current study (1) assessed the prevalence of NREM sleep desaturation in nonhypoxemic patients with chronic obstructive pulmonary disease (COPD) and (2) compared a biological marker of cerebral lesion and neuromuscular function in patients with and without NREM sleep desaturation. One hundred fifteen patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 2 and 3), resting PaO2 of 60-80 mmHg, aged between 40 and 80 y, and without sleep apnea (apnea-hypopnea index sleep recordings. In addition, twenty-nine patients (substudy) were assessed i) for brain impairment by serum S100B (biological marker of cerebral lesion), and ii) for neuromuscular function via motor cortex activation and excitability and maximal voluntary quadriceps strength measurement. A total of 51.3% patients (n = 59) had NREM sleep desaturation (NREMDes). Serum S100B was higher in the NREMDes patients of the substudy (n = 14): 45.1 [Q1: 37.7, Q3: 62.8] versus 32.9 [Q1: 25.7, Q3: 39.5] pg.ml(-1) (P = 0.028). Motor cortex activation and excitability were lower in NREMDes patients (both P = 0.03), but muscle strength was comparable between groups (P = 0.58). Over half the nonhypoxemic COPD patients exhibited NREM sleep desaturation associated with higher values of the cerebral lesion biomarker and lower neural drive reaching the quadriceps during maximal voluntary contraction. The lack of muscle strength differences between groups suggests a compensatory mechanism(s). Altogether, the results are consistent with an involvement of NREM sleep desaturation in COPD brain impairment. The study was registered at www.clinicaltrials.gov as NCT01679782. © 2016 Associated Professional Sleep Societies, LLC.

  9. Higher-order Brain Areas Associated with Real-time Functional MRI Neurofeedback Training of the Somato-motor Cortex.

    Science.gov (United States)

    Auer, Tibor; Dewiputri, Wan Ilma; Frahm, Jens; Schweizer, Renate

    2018-05-15

    Neurofeedback (NFB) allows subjects to learn self-regulation of neuronal brain activation based on information about the ongoing activation. The implementation of real-time functional magnetic resonance imaging (rt-fMRI) for NFB training now facilitates the investigation into underlying processes. Our study involved 16 control and 16 training right-handed subjects, the latter performing an extensive rt-fMRI NFB training using motor imagery. A previous analysis focused on the targeted primary somato-motor cortex (SMC). The present study extends the analysis to the supplementary motor area (SMA), the next higher brain area within the hierarchy of the motor system. We also examined transfer-related functional connectivity using a whole-volume psycho-physiological interaction (PPI) analysis to reveal brain areas associated with learning. The ROI analysis of the pre- and post-training fMRI data for motor imagery without NFB (transfer) resulted in a significant training-specific increase in the SMA. It could also be shown that the contralateral SMA exhibited a larger increase than the ipsilateral SMA in the training and the transfer runs, and that the right-hand training elicited a larger increase in the transfer runs than the left-hand training. The PPI analysis revealed a training-specific increase in transfer-related functional connectivity between the left SMA and frontal areas as well as the anterior midcingulate cortex (aMCC) for right- and left-hand trainings. Moreover, the transfer success was related with training-specific increase in functional connectivity between the left SMA and the target area SMC. Our study demonstrates that NFB training increases functional connectivity with non-targeted brain areas. These are associated with the training strategy (i.e., SMA) as well as with learning the NFB skill (i.e., aMCC and frontal areas). This detailed description of both the system to be trained and the areas involved in learning can provide valuable information

  10. Enduring Effects Of Traumatic Stress On Brain Neuropeptide Y (NPY) and Corticotropin-Releasing Factor (CRF) Systems: Molecular and Neuropharmacologic Studies

    Science.gov (United States)

    2009-12-01

    epoch consisted of a single daily defeat episode as described above on 3 consecutive days. Between each epoch, there was a time-out period of 3 days...2.5 weeks after the final defeat (data not shown). Treatment with twice daily imipramine (i.p., 2.5 mg/kg) for 2.5 weeks, eliminated the effects of...time course of immediate early gene expression in rat brain following acute stress. Neuroscience 64:477–505. ayas CV, Buller KM, Day TA (1999

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

    DEFF Research Database (Denmark)

    Hougaard, Anders; Amin, Faisal Mohammad; Larsson, Henrik B W

    2017-01-01

    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......-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......-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...

  12. 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

  13. 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

  14. 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)

    Smitka, Kvido; 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.

  15. 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.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.)

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

    Science.gov (United States)

    Miller, Gregory A; Crocker, Laura D; Spielberg, Jeffrey M; Infantolino, Zachary P; Heller, Wendy

    2013-01-01

    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. Evidence of other frontal lateralizations, involving distinctions among dimensions of depression and anxiety, make a dichotomous view even more problematic. Recent evidence indicates that positive valence and approach motivation are associated with different areas in the left-hemisphere. Findings that appear contradictory at the level of frontal lobes as the units of analysis can be accommodated because 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.

  20. 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.

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

    International Nuclear Information System (INIS)

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona; Husain, Nuzhat; Srivastava, Savita; Rathore, Ram K.S.; Sarma, Manoj K.; Malik, Gyanendra K.; Das, Vinita; Pradhan, Mandakini; Pandey, Chandra M.; Narayana, Ponnada A.

    2009-01-01

    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.)

  2. 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.)

  3. Intertemporal Decision Making After Brain Injury: Amount-Dependent Steeper Discounting after Frontal Cortex Damage

    Directory of Open Access Journals (Sweden)

    Białaszek Wojciech

    2017-12-01

    Full Text Available Traumatic brain injuries to the frontal lobes are associated with many maladaptive forms of behavior. We investigated the association between brain damage and impulsivity, as measured by the rate of delay discounting (i.e., the extent to which future outcomes are devalued in time. The main aim of this study was to test the hypothesis of steeper discounting of different amounts in a group of patients with frontal lobe damage. We used a delay discounting task in the form of a structured interview. A total of 117 participants were divided into five groups: three neurological groups and two groups without brain damage. Our analyses showed that patients with focal damage to the frontal lobes demonstrated steeper delay discounting than other participants. Other clinical groups demonstrated similar discounting rates. The data pattern related to the magnitude effect on the group level suggested that the magnitude effect is absent in the group of patients with damage to the frontal lobes; however, results were less consistent on an individual level. Amount-dependent discounting was observed in only two groups, the healthy control group and the neurological group with other cortical areas damaged.

  4. Functional MR imaging of the motor cortex in healthy volunteers and patients with brain tumours: qualitative and quantitative results

    Energy Technology Data Exchange (ETDEWEB)

    Fellner, C. [Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Inst. of Medical Physics]|[Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Dept. of Diagnostic Radiology; Schlaier, J.; Schwerdtner, J.; Brawanski, A. [Regensburg Univ. (Germany). Dept. of Radiology; Fellner, F. [Regensburg Univ. (Germany). Dept. of Neurosurgery]|[Oberoesterreichische Landesnervenklinik, Linz (Austria). Dept. of Neuroradiology; Held, P. [Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Dept. of Diagnostic Radiology; Blank, M.; Kalender, W.A. [Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Inst. of Medical Physics

    1999-06-01

    The purpose of this study was to compare functional magnetic resonance (MR) imaging of the motor cortex in healthy volunteers and patients with brain tumours. Functional MR imaging was performed in 14 healthy volunteers and 14 patients with tumours in or near the primary motor cortex with groups being matched for age, sex, and handedness. Functional images were acquired during motion of the right and left hand. Time courses of signal intensity within the contralateral, ipsilateral, and supplementary motor cortex as well as z-maps were calculated, their quality being assessed visually. Mean signal increase between activation and rest were evaluated within the contralateral, ipsilateral, and supplementary motor cortex, the activated area in those regions of interest was measured using z-maps. The quality of functional MR experiments was generally lower in patients than in volunteers. The quantitative results showed a trend towards increased ipsilateral activation in volunteers during left hand compared to right hand motion and in patients during motion of the affected compared to the non-affected hand. Considering quantitative and qualitative results, significantly increased ipsilateral activation was found in patients compared to healthy volunteers. In conclusion, functional MR imaging quality was significantly reduced in patient studies compared to healthy volunteers, even if influences of age, sex, and handedness were excluded. Increased ipsilateral activation was found in patients with brain tumours which can be interpreted by an improved connectivity between both hemispheres. (orig.) [Deutsch] Das Ziel der vorliegenden Studie war ein Vergleich der funktionellen MR-Bildgebung (fMRI: Functional magnetic resonance imaging) des Motorkortex bei gesunden Probanden und Patienten mit Hirntumor. Die funktionelle MR-Bildgebung wurde bei 14 gesunden Probanden und bei 14 Patienten mit einem Tumor im oder nahe des primaeren Motorkortex durchgefuehrt, wobei beide Kollektive

  5. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Lesions of entorhinal cortex produce a calpain-mediated degradation of brain spectrin in dentate gyrus. I. Biochemical studies.

    Science.gov (United States)

    Seubert, P; Ivy, G; Larson, J; Lee, J; Shahi, K; Baudry, M; Lynch, G

    1988-09-06

    Lesions of the rat entorhinal cortex cause extensive synaptic restructuring and perturbation of calcium regulation in the dentate gyrus of hippocampus. Calpain is a calcium-activated protease which has been implicated in degenerative phenomena in muscles and in peripheral nerves. In addition, calpain degrades several major structural neuronal proteins and has been proposed to play a critical role in the morphological changes observed following deafferentation. In this report we present evidence that lesions of the entorhinal cortex produce a marked increase in the breakdown of brain spectrin, a substrate for calpain, in the dentate gyrus. Two lines of evidence indicate that this effect is due to calpain activation: (i) the spectrin breakdown products observed following the lesion are indistinguishable from calpain-generated spectrin fragments in vitro; and (ii) their appearance can be reduced by prior intraventricular in fusion of leupeptin, a calpain inhibitor. Levels of spectrin breakdown products are increased as early as 4 h post-lesion, reach maximal values at 2 days, and remain above normal to some degree for at least 27 days. In addition, a small but significant increase in spectrin proteolysis is also observed in the hippocampus contralateral to the lesioned side in the first week postlesion. At 2 days postlesion the total spectrin immunoreactivity (native polypeptide plus breakdown products) increases by 40%, suggesting that denervation of the dentate gyrus produces not only an increased rate of spectrin degradation but also an increased rate of spectrin synthesis. These results indicate that calpain activation and spectrin degradation are early biochemical events following deafferentation and might well participate in the remodelling of postsynaptic structures. Finally, the magnitude of the observed effects as well as the stable nature of the breakdown products provide a sensitive assay for neuronal pathology.

  7. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Places in the Brain: Bridging Layout and Object Geometry in Scene-Selective Cortex.

    Science.gov (United States)

    Dillon, Moira R; Persichetti, Andrew S; Spelke, Elizabeth S; Dilks, Daniel D

    2017-06-13

    Diverse animal species primarily rely on sense (left-right) and egocentric distance (proximal-distal) when navigating the environment. Recent neuroimaging studies with human adults show that this information is represented in 2 scene-selective cortical regions-the occipital place area (OPA) and retrosplenial complex (RSC)-but not in a third scene-selective region-the parahippocampal place area (PPA). What geometric properties, then, does the PPA represent, and what is its role in scene processing? Here we hypothesize that the PPA represents relative length and angle, the geometric properties classically associated with object recognition, but only in the context of large extended surfaces that compose the layout of a scene. Using functional magnetic resonance imaging adaptation, we found that the PPA is indeed sensitive to relative length and angle changes in pictures of scenes, but not pictures of objects that reliably elicited responses to the same geometric changes in object-selective cortical regions. Moreover, we found that the OPA is also sensitive to such changes, while the RSC is tolerant to such changes. Thus, the geometric information typically associated with object recognition is also used during some aspects of scene processing. These findings provide evidence that scene-selective cortex differentially represents the geometric properties guiding navigation versus scene categorization. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Damian Scarf

    2011-01-01

    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.

  10. 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.

  11. Role of Nitric Oxide in Radioinduced Effects in Developing Brain Cortex

    International Nuclear Information System (INIS)

    Robello, E

    2001-01-01

    Nowadays, prenatal exposure is a very important topic in radiopathology.Unfortunately, pregnant women have been sometimes exposed or have to expose to ionising radiation, for example, during a medical treatment.There are lots of studies made by the International Commission of Radiation Protection (ICRP) about the effects of ionising radiation and the consequences that are suffered by the exposed foetus.Hence, it has been argued that developing mammalian brain is substantially more susceptible to teratogenic insult than most other embryonic and foetal structures.Presumably, this reflects its architectural complexity, its long developmental period, the vulnerability of the undifferentiated neural cell and the inability of the brain to replace lost neurones.Furthermore, there is abundant information on the biological effects caused by prenatal exposure of mammals to ionising radiation.Only two conspicuous effects on brain growth and development have emerged thus far in the study of atomic bomb survivors exposed prenatally in Hiroshima and Nagasaki.These are some cases of severe mental retardation and some of small head size without apparent metal retardation. Additionally, groups within the survivors have shown significantly reduced IQ scores.This increase would be dose-related and, if the shift of IQ had no clear dose threshold, might, in turn, show no threshold.Besides, it has been studied that ionising radiation implies molecular ionisation and excitation in the biological systems.When radiation has a high linear transfer energy (LET) damage may be produce trough energy absorbed directly by the target molecule (direct mechanism).However, when radiation has a low LET (like γ and X radiation), and without forgetting that biological systems are basically aqueous, damage may be produce trough generation of species highly reactive (like free radicals and reactive oxygen species - ROS) by molecules of water which has adsorbed energy radiation (indirect mechanism

  12. Removing the effect of response time on brain activity reveals developmental differences in conflict processing in the posterior medial prefrontal cortex.

    Science.gov (United States)

    Carp, Joshua; Fitzgerald, Kate Dimond; Taylor, Stephan F; Weissman, Daniel H

    2012-01-02

    In functional magnetic resonance imaging (fMRI) studies, researchers often attempt to ensure that group differences in brain activity are not confounded with group differences in mean reaction time (RT). However, even when groups are matched for performance, they may differ in terms of the RT-BOLD relationship: the degree to which brain activity varies with RT on a trial-by-trial basis. Group activation differences might therefore be influenced by group differences in the relationship between brain activity and time on task. Here, we investigated whether correcting for this potential confound alters group differences in brain activity. Specifically, we reanalyzed data from a functional MRI study of response conflict in children and adults, in which conventional analyses indicated that conflict-related activity did not differ between groups. We found that the RT-BOLD relationship was weaker in children than in adults. Consequently, after removing the effect of RT on brain activity, children exhibited greater conflict-related activity than adults in both the posterior medial prefrontal cortex and the right dorsolateral prefrontal cortex. These results identify the RT-BOLD relationship as an important potential confound in fMRI studies of group differences. They also suggest that the magnitude of the RT-BOLD relationship may be a useful biomarker of brain maturity. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Acute infusion of brain-derived neurotrophic factor in the insular cortex promotes conditioned taste aversion extinction.

    Science.gov (United States)

    Rodríguez-Serrano, Luis M; Ramírez-León, Betsabee; Rodríguez-Durán, Luis F; Escobar, Martha L

    2014-12-01

    Brain-derived neurotrophic factor (BDNF) has emerged as one of the most potent molecular mediators not only for synaptic plasticity, but also for the behavioral organism-environment interactions. Our previous studies in the insular cortex (IC), a neocortical region that has been related with acquisition and retention of conditioned taste aversion (CTA), have demonstrated that intracortical microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the basolateral amygdaloid nucleus (Bla)-IC projection and enhances the retention of CTA memory of adult rats in vivo. The aim of the present study was to analyze whether acute BDNF-infusion in the IC modifies the extinction of CTA. Accordingly, animals were trained in the CTA task and received bilateral IC microinfusions of BDNF before extinction training. Our results showed that taste aversion was significantly reduced in BDNF rats from the first extinction trial. Additionally, we found that the effect of BDNF on taste aversion did not require extinction training. Finally we showed that the BDNF effect does not degrade the original taste aversion memory trace. These results emphasize that BDNF activity underlies memory extinction in neocortical areas and support the idea that BDNF is a key regulator and mediator of long-term synaptic modifications. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. 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.

  15. Disturbance of visual search by stimulating to posterior parietal cortex in the brain using transcranial magnetic stimulation

    Science.gov (United States)

    Iramina, Keiji; Ge, Sheng; Hyodo, Akira; Hayami, Takehito; Ueno, Shoogo

    2009-04-01

    In this study, we applied a transcranial magnetic stimulation (TMS) to investigate the temporal aspect for the functional processing of visual attention. Although it has been known that right posterior parietal cortex (PPC) in the brain has a role in certain visual search tasks, there is little knowledge about the temporal aspect of this area. Three visual search tasks that have different difficulties of task execution individually were carried out. These three visual search tasks are the "easy feature task," the "hard feature task," and the "conjunction task." To investigate the temporal aspect of the PPC involved in the visual search, we applied various stimulus onset asynchronies (SOAs) and measured the reaction time of the visual search. The magnetic stimulation was applied on the right PPC or the left PPC by the figure-eight coil. The results show that the reaction times of the hard feature task are longer than those of the easy feature task. When SOA=150 ms, compared with no-TMS condition, there was a significant increase in target-present reaction time when TMS pulses were applied. We considered that the right PPC was involved in the visual search at about SOA=150 ms after visual stimulus presentation. The magnetic stimulation to the right PPC disturbed the processing of the visual search. However, the magnetic stimulation to the left PPC gives no effect on the processing of the visual search.

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

    Science.gov (United States)

    Lajoie, Guillaume; Krouchev, Nedialko I; Kalaska, John F; Fairhall, Adrienne L; Fetz, Eberhard E

    2017-02-01

    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.

  17. 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.

  18. Reduced number of (/sup 3/H)nicotine and (/sup 3/H)acelylcholine binding sites in the frontal cortex of Alzheimer brains

    Energy Technology Data Exchange (ETDEWEB)

    Nordberg, A; Winblad, B

    1986-12-03

    Nicotinic cholinergic receptors were measured in human frontal cortex using (/sup 3/H)nicotine and (/sup 3/H)acetylcholine (in the presence of atropine) as receptor ligands. A parallel marked reduction in number of (/sup 3/H)nicotine (52%, P<0.01) and (/sup 3/H)acetylcholine (-55%, P<0.05) binding was found in the frontal cortex of Alzheimer brains (AD/SDAT) when compared to age-matched control brains. As a comparison the number of muscarinic receptors was quantified using (/sup 3/H)quinuclidinyl benzilate and found to be significantly increased (+23%, P<0.01) in AD/SDAT compared to controls. 26 refs.

  19. Proteomic analysis of post-nuclear supernatant fraction and percoll-purified membranes prepared from brain cortex of rats exposed to increasing doses of morphine

    Czech Academy of Sciences Publication Activity Database

    Ujčíková, Hana; Eckhardt, Adam; Kagan, Dmytro; Roubalová, Lenka; Svoboda, Petr

    2014-01-01

    Roč. 12, Feb 14 (2014), s. 11 ISSN 1477-5956 R&D Projects: GA ČR(CZ) GAP207/12/0919; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : morphine * long-term exposure * rat brain cortex * isolated plasma membranes * post-nuclear supernatant * 2D electrophoresis Subject RIV: CE - Biochemistry Impact factor: 1.725, year: 2014

  20. Nematode neuropeptides as transgenic nematicides.

    Directory of Open Access Journals (Sweden)

    Neil D Warnock

    2017-02-01

    Full Text Available 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.

  1. 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.

  2. 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

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

    International Nuclear Information System (INIS)

    Chang, Seong-Hun; Jung, In-Soo; Han, Gi-Yeon; Kim, Nam-Hee; Kim, Hyun-Jung; Kim, Chan-Wha

    2013-01-01

    Highlights: ► A transgenic mouse model expressing NSE-htau23 was used. ► 2D-gel electrophoresis to analyze the cortex proteins of transgenic mice was used. ► Differentially expressed spots in different stages of AD were identified. ► GSTP1 and CAII were downregulated with the progression of AD. ► 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 study of up- and down-regulation of proteins during the progression of AD helps to explain the mechanisms associated with neuronal

  4. The determination of trace metals by INAA in cortex cerebellum and putamen of human brain and in their neuromelanins

    International Nuclear Information System (INIS)

    Giaveri, G.; Rizzio, E.; Bergamaschi, L.; Gallorini, M.; Zecca, L.

    2002-01-01

    Instrumental Neutron Activation Analysis (INAA) was used for all the measurements. Irradiations were performed at the Triga Mark II (General Atomic - USA) research reactor of the University of Pavia. Depending on the elements to be determined, two different irradiation procedures were followed: Short irradiations were performed in the pneumatic irradiation facility at a neutron flux of 5x10 12 n x cm -2 x s - 1 . Samples and standards sealed in plastic vials were irradiated for 5 minutes. Long irradiations were carried out in the central thimble facility at a nominal neutron flux of 1013 n x cm-2 x s - 1. Samples and standards were sealed in quartz vials and then neutron irradiated for 40 h. For the gamma spectra evaluation HPGe (gamma -x) detectors (ORTEC - USA) coupled to computerized multichannel analysers (ORTEC ADCAM - USA) were used. The concentrations of trace elements in Cortex, Cerebellum, Putamen and in their Neuromelanins are reported. Fe is the most abundant element in tissues, followed by Zinc. The ability of NMs to sequestrate metals is well shown, being their concentrations in NMs much higher than in their respective tissues, where some of them (Hg, Mo) were not even detectable. Strong differences are shown between the different pigments in interaction with metals. NM from SN shows a higher affinity for iron than all the other pigments isolated from other brain areas; nevertheless, the tissue that contains the highest concentration of this metal is PU and not SN. These results would confirm that NM from SN plays a protective role in neurons by quenching Fenton's reaction, so far considered the cause of the pathogenesis of PD. A protective role could be played by the other pigments as well, as the concentrations of analysed elements show that they bind large amounts of potentially toxic metals different from iron. This might be explained as the need of the neurons to defend themselves from the toxicity of this metal by the development of a specific

  5. Right parietal cortex and calculation processing: intraoperative functional mapping of multiplication and addition in patients affected by a brain tumor.

    Science.gov (United States)

    Della Puppa, Alessandro; De Pellegrin, Serena; d'Avella, Elena; Gioffrè, Giorgio; Munari, Marina; Saladini, Marina; Salillas, Elena; Scienza, Renato; Semenza, Carlo

    2013-11-01

    The role of parietal areas in number processing is well known. The significance of intraoperative functional mapping of these areas has been only partially explored, however, and only a few discordant data are available in the surgical literature with regard to the right parietal lobe. The purpose of this study was to evaluate the clinical impact of simple calculation in cortical electrostimulation of right-handed patients affected by a right parietal brain tumor. Calculation mapping in awake surgery was performed in 3 right-handed patients affected by high-grade gliomas located in the right parietal lobe. Preoperatively, none of the patients presented with calculation deficits. In all 3 cases, after sensorimotor and language mapping, cortical and intraparietal sulcus areas involved in single-digit multiplication and addition calculations were mapped using bipolar electrostimulation. In all patients, different sites of the right parietal cortex, mainly in the inferior lobule, were detected as being specifically related to calculation (multiplication or addition). In 2 patients the intraparietal sulcus was functionally specific for multiplication. No functional sites for language were detected. All sites functional for calculation were spared during tumor resection, which was complete in all cases without postoperative neurological deficits. These findings provide intraoperative data in support of an anatomofunctional organization for multiplication and addition within the right parietal area. Furthermore, the study shows the potential clinical relevance of intraoperative mapping of calculation in patients undergoing surgery in the right parietal area. Further and larger studies are needed to confirm these data and assess whether mapped areas are effectively essential for function.

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

    Czech Academy of Sciences Publication Activity Database

    Salaj, M.; Druga, Rastislav; Cerman, J.; Kubová, Hana; Barinka, F.

    2015-01-01

    Roč. 1627, Nov 19 (2015), s. 201-215 ISSN 0006-8993 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : retrosplenial cortex * calretinin * parvalbumin * interneurons * calcium-binding proteins * perirhinal cortex Subject RIV: FH - Neurology Impact factor: 2.561, year: 2015

  7. The impact of lysine and arginine ratios in plant-based protein diets on appetite, growth performance and gene expression of brain neuropeptide Y (NPY) and cholecystokinin (CCK) in juvenile cobia (Rachycentron canadum)

    OpenAIRE

    Nguyen, Minh Van

    2013-01-01

    Aquaculture of cobia, Rachycentron canadum is hampered by lack of good feeding protocols and nutritionally optimized diets. Studies on the role of appetite and feeding behavior regulating neuropeptides in cobia have not been pursued to date. The current study initially assessed the impact of plant-based protein diets with different lysine (L) to arginine (A) ratios on appetite and feed intake, feed efficiencies, growth performance, and the deposition of protein and lipid in juv...

  8. Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus.

    Science.gov (United States)

    Thomsen, Kirsten; Yokota, Takashi; Hasan-Olive, Md Mahdi; Sherazi, Niloofar; Fakouri, Nima Borhan; Desler, Claus; Regnell, Christine Elisabeth; Larsen, Steen; Rasmussen, Lene Juel; Dela, Flemming; Bergersen, Linda Hildegard; Lauritzen, Martin

    2018-01-01

    Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB m/m ) and C57Bl/6 (WT) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB m/m hippocampus, but not in CSB m/m cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased with age. Notably, an inverse correlation between heterogeneity and CI was found in both genotypes, indicating that heterogeneity reflects mitochondrial dysfunction. The ratio between fission and fusion gene expression reflected age-related alterations in mitochondrial morphology but not heterogeneity. Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSB m/m compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event in brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species

    Directory of Open Access Journals (Sweden)

    Débora Jardim-Messeder

    2017-12-01

    Full Text Available Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion share with non-primates, including artiodactyls (the typical prey of large carnivorans, roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal

  10. Neuropeptides in Lower Urinary Tract (LUT) Function

    Science.gov (United States)

    Arms, Lauren; Vizzard, Margaret A.

    2014-01-01

    Numerous neuropeptide/receptor systems including vasoactive intestinal polypeptide, pituitary adenylate cyclase-activating polypeptide, calcitonin gene-related peptide, substance P, neurokinin A, bradykinin, and endothelin-1 are expressed in the lower urinary tract (LUT) in both neural and non-neural (e.g., urothelium) components. LUT neuropeptide immunoreactivity is present in afferent and autonomic efferent neurons innervating the bladder and urethra and in the urothelium of the urinary bladder. Neuropeptides have tissue-specific distributions and functions in the LUT and exhibit neuroplastic changes in expression and function with LUT dysfunction following neural injury, inflammation and disease. LUT dysfunction with abnormal voiding including urinary urgency, increased voiding frequency, nocturia, urinary incontinence and pain may reflect a change in the balance of neuropeptides in bladder reflex pathways. LUT neuropeptide/receptor systems may represent potential targets for therapeutic intervention. PMID:21290237

  11. High diversity in neuropeptide immunoreactivity patterns among three closely related species of Dinophilidae (Annelida)

    DEFF Research Database (Denmark)

    Kerbl, Alexandra; Conzelmann, Markus; Jékely, Gáspár

    2017-01-01

    Neuropeptides are conserved metazoan signaling molecules, and represent useful markers for comparative investigations on the morphology and function of the nervous system. However, little is known about the variation of neuropeptide expression patterns across closely related species in invertebrate...... groups other than insects. In this study, we compare the immunoreactivity patterns of 14 neuropeptides in three closely related microscopic dinophilid annelids (Dinophilus gyrociliatus, D. taeniatus and Trilobodrilus axi). The brains of all three species were found to consist of around 700 somata...... species. FMRFamide, MLD/pedal peptide, allatotropin, RNamide, excitatory peptide, and FVRIamide showed a broad localization within the brain, while calcitonin, SIFamide, vasotocin, RGWamide, DLamide, FLamide, FVamide, MIP, and serotonin were present in fewer cells in demarcated regions. The different...

  12. Enhanced inhibitory control by neuropeptide Y Y5 receptor blockade in rats.

    Science.gov (United States)

    Bari, A; Dec, A; Lee, A W; Lee, J; Song, D; Dale, E; Peterson, J; Zorn, S; Huang, X; Campbell, B; Robbins, T W; West, A R

    2015-03-01

    The neuropeptide Y (NPY) system acts in synergy with the classic neurotransmitters to regulate a large variety of functions including autonomic, affective, and cognitive processes. Research on the effects of NPY in the central nervous system has focused on food intake control and affective processes, but growing evidence of NPY involvement in attention-deficit/hyperactivity disorder (ADHD) and other psychiatric conditions motivated the present study. We tested the effects of the novel and highly selective NPY Y5 receptor antagonist Lu AE00654 on impulsivity and the underlying cortico-striatal circuitry in rats to further explore the possible involvement of the NPY system in pathologies characterized by inattention and impulsive behavior. A low dose of Lu AE00654 (0.03 mg/kg) selectively facilitated response inhibition as measured by the stop-signal task, whereas no effects were found at higher doses (0.3 and 3 mg/kg). Systemic administration of Lu AE00654 also enhanced the inhibitory influence of the dorsal frontal cortex on neurons in the caudate-putamen, this fronto-striatal circuitry being implicated in the executive control of behavior. Finally, by locally injecting a Y5 agonist, we observed reciprocal activation between dorsal frontal cortex and caudate-putamen neurons. Importantly, the effects of the Y5 agonist were attenuated by pretreatment with Lu AE00654, confirming the presence of Y5 binding sites modulating functional interactions within frontal-subcortical circuits. These results suggest that the NPY system modulates inhibitory neurotransmission in brain areas important for impulse control, and may be relevant for the treatment of pathologies such as ADHD and drug abuse.

  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. 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

  15. Spontaneous brain activity in the sensorimotor cortex in amyotrophic lateral sclerosis can be negatively regulated by corticospinal fiber integrity.

    Science.gov (United States)

    Sako, Wataru; Abe, Takashi; Izumi, Yuishin; Yamazaki, Hiroki; Matsui, Naoko; Harada, Masafumi; Kaji, Ryuji

    2017-05-01

    Previous studies failed to detect reduced value of the amplitude of low frequency fluctuation (ALFF) derived from resting state functional magnetic resonance imaging in the primary motor cortex in amyotrophic lateral sclerosis (ALS) though primary motor cortex was mainly affected with ALS. We aimed to investigate the cause of masking the abnormality in the primary motor cortex in ALS and usefulness of ALFF for differential diagnosis among diseases showing muscle weakness. We enrolled ten patients with ALS and eleven disease controls showing muscle weakness. Voxel-wise analysis revealed that significant reduction of ALFF value was present in the right sensorimotor cortex in ALS. There was a significant negative correlation between ALFF value in the right sensorimotor cortex and fractional anisotropy (FA) value in the posterior limbs of the internal capsule (PLIC). For a diagnostic tool, the area under receiver operating characteristic curve improved if the ALS patients with disease duration >1 year were excluded. The present findings raised the possibility of usefulness of ALFF value in the sensorimotor cortex for differential diagnosis of ALS, and supported the notion that adjustment for FA value in the PLIC could improve accuracy.

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

    International Nuclear Information System (INIS)

    Khosravie, H.R.

    2000-01-01

    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 effects of thumb motor cortex of normal volunteer by using conventional standard 1.5 T imager and optimized gradient echo techniques. Activating sensory and motor stimulations can be led to, respective cortical area of that stimulation by which oxygenated blood flow is increased in that area (Bold contrast). By designing of a T 2* sensitized gradient echo protocol, thumb's sensory and motor cortex activation is evaluated. A protocol known as F AST i n picker system with the following specifications was used for F MRI: Band Width:24 Hz/Pixel, Tr=101 m Sec , T E=49 m Sec , Flip Angle= 10 deg., N E X=1 ,Slice thickness=5-7 mm F O V=250 mm ,Matrix=128*128 and total scan time= 14 Sec. Stimulation of the motor cortex was performed by periodic movement of dominant thumb in up-down and right-left direction within a Ls hape trajectory of plastic sheet with a frequency about 2 Hz. Then, acquired images in rest and stimulation period were evaluated by S P M 97, S P M 99 b software. 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

  17. 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

  18. The neurobiological role of the dorsolateral prefrontal cortex in recovery from trauma. Longitudinal brain imaging study among survivors of the South Korean subway disaster.

    Science.gov (United States)

    Lyoo, In Kyoon; Kim, Jieun E; Yoon, Sujung J; Hwang, Jaeuk; Bae, Sujin; Kim, Dajung J

    2011-07-01

    A multiwave longitudinal neuroimaging study in a cohort of direct survivors of a South Korean subway disaster, most of whom recovered from posttraumatic stress disorder 5 years after trauma, provided a unique opportunity to investigate the brain correlates of recovery from a severe psychological trauma. To investigate region-specific brain mobilization during successful recovery from posttraumatic stress disorder by assessing cortical thickness multiple times from early after trauma to recovery, and to examine whether a brain-derived neurotrophic factor gene polymorphism was associated with this brain mobilization. Five-year follow-up case-control study conducted from 2003-2007. Seoul National University and Hospital. Thirty psychologically traumatized disaster survivors and 36 age- and sex-matched control group members recruited from the disaster registry and local community, respectively, who contributed 156 high-resolution brain magnetic resonance images during 3 waves of assessments. Cerebral cortical thickness measured in high-resolution anatomic magnetic resonance images using a validated cortical thickness analysis tool and its prospective changes from early after trauma to recovery in trauma-exposed individuals and controls. Trauma-exposed individuals had greater dorsolateral prefrontal cortical (DLPFC) thickness 1.42 years after trauma (right DLPFC, 5.4%; left superior frontal cortex, 5.8%; and left inferior frontal cortex, 5.3% [all clusters, P ≤ .01]) relative to controls. Thicknesses gradually normalized over time during recovery. We found a positive linear trend, with trauma-exposed individuals with a valine/valine genotype having the greatest DLPFC cortical thickness, followed by those with a methionine genotype and controls (P < .001 for trend). Greater DLPFC thickness was associated with greater posttraumatic stress disorder symptom reductions and better recovery. The DLPFC region might play an important role in psychological recovery from a

  19. Gene expression of fatty acid transport and binding proteins in the blood-brain barrier and the cerebral cortex of the rat: differences across development and with different DHA brain status.

    Science.gov (United States)

    Pélerin, Hélène; Jouin, Mélanie; Lallemand, Marie-Sylvie; Alessandri, Jean-Marc; Cunnane, Stephen C; Langelier, Bénédicte; Guesnet, Philippe

    2014-11-01

    Specific mechanisms for maintaining docosahexaenoic acid (DHA) concentration in brain cells but also transporting DHA from the blood across the blood-brain barrier (BBB) are not agreed upon. Our main objective was therefore to evaluate the level of gene expression of fatty acid transport and fatty acid binding proteins in the cerebral cortex and at the BBB level during the perinatal period of active brain DHA accretion, at weaning, and until the adult age. We measured by real time RT-PCR the mRNA expression of different isoforms of fatty acid transport proteins (FATPs), long-chain acyl-CoA synthetases (ACSLs), fatty acid binding proteins (FABPs) and the fatty acid transporter (FAT)/CD36 in cerebral cortex and isolated microvessels at embryonic day 18 (E18) and postnatal days 14, 21 and 60 (P14, P21 and P60, respectively) in rats receiving different n-3 PUFA dietary supplies (control, totally deficient or DHA-supplemented). In control rats, all the genes were expressed at the BBB level (P14 to P60), the mRNA levels of FABP5 and ACSL3 having the highest values. Age-dependent differences included a systematic decrease in the mRNA expressions between P14-P21 and P60 (2 to 3-fold), with FABP7 mRNA abundance being the most affected (10-fold). In the cerebral cortex, mRNA levels varied differently since FATP4, ACSL3 and ACSL6 and the three FABPs genes were highly expressed. There were no significant differences in the expression of the 10 genes studied in n-3 deficient or DHA-supplemented rats despite significant differences in their brain DHA content, suggesting that brain DHA uptake from the blood does not necessarily require specific transporters within cerebral endothelial cells and could, under these experimental conditions, be a simple passive diffusion process. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Early stress is associated with alterations in the orbitofrontal cortex: a tensor-based morphometry investigation of brain structure and behavioral risk.

    Science.gov (United States)

    Hanson, Jamie L; Chung, Moo K; Avants, Brian B; Shirtcliff, Elizabeth A; Gee, James C; Davidson, Richard J; Pollak, Seth D

    2010-06-02

    Individuals who experience early adversity, such as child maltreatment, are at heightened risk for a broad array of social and health difficulties. However, little is known about how this behavioral risk is instantiated in the brain. Here we examine a neurobiological contribution to individual differences in human behavior using methodology appropriate for use with pediatric populations paired with an in-depth measure of social behavior. We show that alterations in the orbitofrontal cortex among individuals who experienced physical abuse are related to social difficulties. These data suggest a biological mechanism linking early social learning to later behavioral outcomes.

  1. Bombyx neuropeptide G protein-coupled receptor A7 is the third cognate receptor for short neuropeptide F from silkworm.

    Science.gov (United States)

    Ma, Qiang; Cao, Zheng; Yu, Yena; Yan, Lili; Zhang, Wenjuan; Shi, Ying; Zhou, Naiming; Huang, Haishan

    2017-12-15

    The short neuropeptide F (sNPF) neuropeptides, closely related to vertebrate neuropeptide Y (NPY), have been suggested to exert pleiotropic effects on many physiological processes in insects. In the silkworm ( Bombyx mori ) two orphan G protein-coupled receptors, Bombyx neuropeptide G protein-coupled receptor (BNGR) A10 and A11, have been identified as cognate receptors for sNPFs, but other sNPF receptors and their signaling mechanisms in B. mori remain unknown. Here, we cloned the full-length cDNA of the orphan receptor BNGR-A7 from the brain of B. mori larvae and identified it as a receptor for Bombyx sNPFs. Further characterization of signaling and internalization indicated that BNGR-A7, -A10, and -A11 are activated by direct interaction with synthetic Bombyx sNPF-1 and -3 peptides. This activation inhibited forskolin or adipokinetic hormone-induced adenylyl cyclase activity and intracellular Ca 2+ mobilization via a G i/o -dependent pathway. Upon activation by sNPFs, BNGR-A7, -A10, and -A11 evoked ERK1/2 phosphorylation and underwent internalization. On the basis of these findings, we designated the receptors BNGR-A7, -A10, and -A11 as Bommo -sNPFR-1, -2, and -3, respectively. Moreover, the results obtained with quantitative RT-PCR analysis revealed that the three Bombyx sNPF receptor subtypes exhibit differential spatial and temporal expression patterns, suggesting possible roles of sNPF signaling in the regulation of a wide range of biological processes. Our findings provide the first in-depth information on sNPF signaling for further elucidation of the roles of the Bombyx sNPF/sNPFR system in the regulation of physiological activities. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. 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...

  3. 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.

  4. Coordinated Gene Expression of Neuroinflammatory and Cell Signaling Markers in Dorsolateral Prefrontal Cortex during Human Brain Development and Aging

    OpenAIRE

    Primiani, Christopher T.; Ryan, Veronica H.; Rao, Jagadeesh S.; Cam, Margaret C.; Ahn, Kwangmi; Modi, Hiren R.; Rapoport, Stanley I.

    2014-01-01

    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...

  5. Metabolism of glucose in brain of patients with Parkinson's disease. Studies on /sup 11/C-glucose metabolism in the striatum and cerebral cortex during medication or interruption of medication by positron emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Yokoi, Fuji; Ando, Kazuya; Iio, Masaaki

    1984-12-01

    We examined /sup 11/C accumulation by positron emission computed tomography in the region of interest (ROI) in the brain of 8 patients with Parkinson's disease and 5 normal controls when administered with /sup 11/C-Glucose (per os). /sup 11/C-Glucose was prepared from /sup 11/CO/sub 2/ by photosynthesis. 1) No significant difference was observed in the /sup 11/C accumulation in the striatum and cerebral cortex (frontal cortex, temporal cortex and occipital cortex) in 4 patients with Parkinson's disease between continuous medication and 7--10 day interruption of medication. 2) No difference was observed in the /sup 11/C accumulation in the striatum and cerebral cortex between 8 patients with Parkinson's disease and 5 normal controls. (author).

  6. Effect of Low Level Laser Irradiation at Wavelengths 488 and 515 nm on Glutamate Neurotransmitter in Mitochondria of Visual Brain Cortex in Albino Rat

    International Nuclear Information System (INIS)

    Omran, M.F.; El-Ahdal, M.A.; El-Kady, M.H.; Yousri, R.M.

    2004-01-01

    The presence of glutamate in the visual cortex and mitochondria could be used as a measure for the argon laser effect having wavelengths 488 and 515 nm, on the mitochondria. A comparative response for the bound and free glutamate was found. Irradiation with different energies 0.2, 0.5 and 1.0 J for both wavelengths were accomplished. This study makes us to recommend the advantage of using argon laser having wavelength 515 nm to enhance the blocking of glutamate and hence the reduction of brain toxicity. Most of the energy required for cellular functions comes from mitochondria (Shepherd, 1994). Glutamate, which is present in central nervous system at very high level is essential for brain intermediary metabolism (Frazer et al., 1994; Meldrum et al., 2000 and Blumcke et al., 2000). Glutamate is enriched in synaptic vesicles, the subcellular organelles, which are associated with the storage and release of neurotransmitters. Also, biochemical evidence for glutamate as neurotransmitter in fibers from the visual cortex to the subcortical visual relay nuclei has been indicated (Fose and Fonnum, 1987 and George, 1998)

  7. Effect of Electromagnetic Radiation Exposure on Histology and DNA Content of the Brain Cortex and Hypothalamus of Young and Adult Male Albino Rats

    International Nuclear Information System (INIS)

    Othman, A.I.; Othman, A.I.

    2012-01-01

    Concerns have been raised regarding the potential adverse effects of exposure to electromagnetic radiation (EMR) arising from mobile phone. The present study investigates the effect of the daily exposure of adult and young rats to EMR for 1 hour (at a frequency of 900 MHz, a power density of 0.02 mW/cm 2 and an average specific absorption rate of 1.165 W/kg) on the DNA content and tissue architecture of the cortex and hypothalamus of the rat brain. Both young and adult rats were sacrificed at two intervals, after 4 months of daily EMR exposure and after 1 month of stopping the exposure. The present results showed a significant increase in the DNA intensity of young and adult rats in both areas after 4 months of daily EMR exposure. However, decreased DNA content around the normal level was observed after one month of stopping the exposure. Light microscopic examination of irradiated rats revealed edema, vacuolation, necrosis and proliferated glial cells. Stopping EMR exposure showed mild amelioration in the structural damage of the cerebral cortex of young animals, however, most drastic changes still persisted in the other animals. In conclusion, these data may confirm the neurotoxic risks arising from the extensive use of mobile phones that may alter the brain histology and impair its function

  8. [Effect of electro-acupuncture on metabolites in the cerebral cortex of ulcerative colitis rats based on Pi/Wei-brain related theory].

    Science.gov (United States)

    Yang, Yang; Zhao, Ji-lan; Hou, Tian-shu; Han, Xiao-xia; Zhao, Zheng-yu; Peng, Xiao-hua; Wu, Qiao-Feng

    2014-10-01

    To study the effect of electro-acupuncture (EA) at points along Foot Yangming Channel on metabolite of ulcerative colitis (UC) rats' cerebral cortex and to identify key metabolites by referring to Pi/Wei-brain related theory in Chinese medicine (CM). The UC rat model was set up by dextran sulfate sodium (DSS) method. Male SD rats were randomly divided into the model group and the EA group, 13 in each group. Another 13 rats were recruited as the blank control group. Rats in the blank control group and the model group received no EA. EA was performed at Zusanli (ST36), Shangjuxu (ST37), and Tianshu (ST25) for 5 days by using disperse-dense wave. Then all rats were sacrificed. Their recto-colon and the ileocecal junction were pathomorphologically observed by light microscope and transmission electron microscope (TEM). Cerebral cortexes were extracted. Water-soluble and lipid-soluble brain tissue metabolites were respectively extracted for metabolic research using 1H nuclear magnetic resonance (1H-NMR). EA could obviously improve the general condition of UC model rats, decrease the value of DAI, reduce the infiltration of inflammatory cells in the intestinal tract, stabilize structures such as mitochondria, endoplasmic reticulum and so on (P theory.

  9. 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

  10. Activation of dominant hemisphere association cortex during naming as a function of cognitive performance in mild traumatic brain injury: Insights into mechanisms of lexical access

    Directory of Open Access Journals (Sweden)

    Mihai Popescu

    2017-01-01

    Full Text Available Patients with a history of mild traumatic brain injury (mTBI and objective cognitive deficits frequently experience word finding difficulties in normal conversation. We sought to improve our understanding of this phenomenon by determining if the scores on standardized cognitive testing are correlated with measures of brain activity evoked in a word retrieval task (confrontational picture naming. The study participants (n = 57 were military service members with a history of mTBI. The General Memory Index (GMI determined after administration of the Rivermead Behavioral Memory Test, Third Edition, was used to assign subjects to three groups: low cognitive performance (Group 1: GMI ≤ 87, n = 18, intermediate cognitive performance (Group 2: 88 ≤ GMI ≤ 99, n = 18, and high cognitive performance (Group 3: GMI ≥ 100, n = 21. Magnetoencephalography data were recorded while participants named eighty pictures of common objects. Group differences in evoked cortical activity were observed relatively early (within 200 ms from picture onset over a distributed network of left hemisphere cortical regions including the fusiform gyrus, the entorhinal and parahippocampal cortex, the supramarginal gyrus and posterior part of the superior temporal gyrus, and the inferior frontal and rostral middle frontal gyri. Differences were also present in bilateral cingulate cortex and paracentral lobule, and in the right fusiform gyrus. All differences reflected a lower amplitude of the evoked responses for Group 1 relative to Groups 2 and 3. These findings may indicate weak afferent inputs to and within an extended cortical network including association cortex of the dominant hemisphere in patients with low cognitive performance. The association between word finding difficulties and low cognitive performance may therefore be the result of a diffuse pathophysiological process affecting distributed neuronal networks serving a wide range of cognitive

  11. Brain metabolism and extracellular space diffusion parameters during and after transient global hypoxia in the rat cortex

    Czech Academy of Sciences Publication Activity Database

    Zoremba, N.; Homola, Aleš; Rossaint, R.; Syková, Eva

    2007-01-01

    Roč. 203, - (2007), s. 34-41 ISSN 0014-4886 R&D Projects: GA MŠk 1M0538; GA MŠk LC554 Institutional research plan: CEZ:AV0Z50390512 Keywords : Hypoxia * Cortex * Recovery Subject RIV: FH - Neurology Impact factor: 3.982, year: 2007

  12. Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide

    Science.gov (United States)

    Barde, Swapnali; Rüegg, Joelle; Prud’homme, Josée; Ekström, Tomas J.; Palkovits, Miklos; Turecki, Gustavo; Bagdy, Gyorgy; Ihnatko, Robert; Theodorsson, Elvar; Juhasz, Gabriella; Diaz-Heijtz, Rochellys; Mechawar, Naguib; Hökfelt, Tomas G. M.

    2016-01-01

    Major depressive disorder (MDD) is a substantial burden to patients, families, and society, but many patients cannot be treated adequately. Rodent experiments suggest that the neuropeptide galanin (GAL) and its three G protein-coupled receptors, GAL1–3, are involved in mood regulation. To explore the translational potential of these results, we assessed the transcript levels (by quantitative PCR), DNA methylation status (by bisulfite pyrosequencing), and GAL peptide by RIA of the GAL system in postmortem brains from depressed persons who had committed suicide and controls. Transcripts for all four members were detected and showed marked regional variations, GAL and galanin receptor 1 (GALR1) being most abundant. Striking increases in GAL and GALR3 mRNA levels, especially in the noradrenergic locus coeruleus and the dorsal raphe nucleus, in parallel with decreased DNA methylation, were found in both male and female suicide subjects as compared with controls. In contrast, GAL and GALR3 transcript levels were decreased, GALR1 was increased, and DNA methylation was increased in the dorsolateral prefrontal cortex of male suicide subjects, however, there were no changes in the anterior cingulate cortex. Thus, GAL and its receptor GALR3 are differentially methylated and expressed in brains of MDD subjects in a region- and sex-specific manner. Such an epigenetic modification in GALR3, a hyperpolarizing receptor, might contribute to the dysregulation of noradrenergic and serotonergic neurons implicated in the pathogenesis of MDD. Thus, one may speculate that a GAL3 antagonist could have antidepressant properties by disinhibiting the firing of these neurons, resulting in increased release of noradrenaline and serotonin in forebrain areas involved in mood regulation. PMID:27940914

  13. Resting-state brain activity in the motor cortex reflects task-induced activity: A multi-voxel pattern analysis.

    Science.gov (United States)

    Kusano, Toshiki; Kurashige, Hiroki; Nambu, Isao; Moriguchi, Yoshiya; Hanakawa, Takashi; Wada, Yasuhiro; Osu, Rieko

    2015-08-01

    It has been suggested that resting-state brain activity reflects task-induced brain activity patterns. In this study, we examined whether neural representations of specific movements can be observed in the resting-state brain activity patterns of motor areas. First, we defined two regions of interest (ROIs) to examine brain activity associated with two different behavioral tasks. Using multi-voxel pattern analysis with regularized logistic regression, we designed a decoder to detect voxel-level neural representations corresponding to the tasks in each ROI. Next, we applied the decoder to resting-state brain activity. We found that the decoder discriminated resting-state neural activity with accuracy comparable to that associated with task-induced neural activity. The distribution of learned weighted parameters for each ROI was similar for resting-state and task-induced activities. Large weighted parameters were mainly located on conjunctive areas. Moreover, the accuracy of detection was higher than that for a decoder whose weights were randomly shuffled, indicating that the resting-state brain activity includes multi-voxel patterns similar to the neural representation for the tasks. Therefore, these results suggest that the neural representation of resting-state brain activity is more finely organized and more complex than conventionally considered.

  14. 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.

  15. Low-frequency brain stimulation to the left dorsolateral prefrontal cortex increases the negative impact of social exclusion among those high in personal distress.

    Science.gov (United States)

    Fitzgibbon, Bernadette Mary; Kirkovski, Melissa; Bailey, Neil Wayne; Thomson, Richard Hilton; Eisenberger, Naomi; Enticott, Peter Gregory; Fitzgerald, Paul Bernard

    2017-06-01

    The dorsolateral prefrontal cortex (DLPFC) is thought to play a key role in the cognitive control of emotion and has therefore, unsurprisingly, been implicated in the regulation of physical pain perception. This brain region may also influence the experience of social pain, which has been shown to activate similar neural networks as seen in response to physical pain. Here, we applied sham or active low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC, previously shown to exert bilateral effects in pain perception, in healthy participants. Following stimulation, participants played the "Cyberball Task"; an online ball-tossing game in which the subject participant is included or excluded. Compared to sham, rTMS did not modulate behavioural response to social exclusion. However, within the active rTMS group only, greater trait personal distress was related to enhanced negative outcomes to social exclusion. These results add further support to the notion that the effect of brain stimulation is not homogenous across individuals, and indicates the need to consider baseline individual differences when assessing response to brain stimulation. This seems particularly relevant in social neuroscience investigations, where trait factors may have a meaningful effect.

  16. Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

    Directory of Open Access Journals (Sweden)

    L. Yang

    2016-01-01

    Full Text Available The timing and mechanisms of protection by hyperbaric oxygenation (HBO in hypoxic-ischemic brain damage (HIBD have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.

  17. Age-related differences in metabolites in the posterior cingulate cortex and hippocampus of normal ageing brain: A 1H-MRS study

    International Nuclear Information System (INIS)

    Reyngoudt, Harmen; Claeys, Tom; Vlerick, Leslie; Verleden, Stijn; Acou, Marjan; Deblaere, Karel; De Deene, Yves; Audenaert, Kurt; Goethals, Ingeborg; Achten, Eric

    2012-01-01

    Objective: To study age-related metabolic changes in N-acetylaspartate (NAA), total creatine (tCr), choline (Cho) and myo-inositol (Ins). Materials and methods: Proton magnetic resonance spectroscopy ( 1 H-MRS) was performed in the posterior cingulate cortex (PCC) and the left hippocampus (HC) of 90 healthy subjects (42 women and 48 men aged 18–76 years, mean ± SD, 48.4 ± 16.8 years). Both metabolite ratios and absolute metabolite concentrations were evaluated. Analysis of covariance (ANCOVA) and linear regression were used for statistical analysis. Results: Metabolite ratios Ins/tCr and Ins/H 2 O were found significantly increased with age in the PCC (P 2 O was only observed in the PCC (P 1 H-MRS results in these specific brain regions can be important to differentiate normal ageing from age-related pathologies such as mild cognitive impairment (MCI) and Alzheimer's disease.

  18. Walk-related mimic word activates the extrastriate visual cortex in the human brain: an fMRI study.

    Science.gov (United States)

    Osaka, Naoyuki

    2009-03-02

    I present an fMRI study demonstrating that a mimic word highly suggestive of human walking, heard by the ear with eyes closed, significantly activates the visual cortex located in extrastriate occipital region (BA19, 18) and superior temporal sulcus (STS) while hearing non-sense words that do not imply walk under the same task does not activate these areas in humans. I concluded that BA19 and 18 would be a critical region for generating visual images of walking and related intentional stance, respectively, evoked by an onomatopoeia word that implied walking.

  19. A word expressing affective pain activates the anterior cingulate cortex in the human brain: an fMRI study.

    Science.gov (United States)

    Osaka, Naoyuki; Osaka, Mariko; Morishita, Masanao; Kondo, Hirohito; Fukuyama, Hidenao

    2004-08-12

    We present an fMRI study demonstrating that an onomatopoeia word highly suggestive of subjective pain, heard by the ear, significantly activates the anterior cingulate cortex (ACC) while hearing non-sense words that did not imply affective pain under the same task does not activate this area in humans. We concluded that the ACC would be a pivotal locus for perceiving affective pain evoked by an onomatopoeia word that implied affective pain closely associated with the unpleasantness of pain. We suggest that the pain affect sustained by pain unpleasantness may depend on ACC-prefrontal cortical interactions that modify cognitive evaluation of emotions associated with word-induced pain.

  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.

  1. How does the brain rapidly learn and reorganize view-invariant and position-invariant object representations in the inferotemporal cortex?

    Science.gov (United States)

    Cao, Yongqiang; Grossberg, Stephen; Markowitz, Jeffrey

    2011-12-01

    All primates depend for their survival on being able to rapidly learn about and recognize objects. Objects may be visually detected at multiple positions, sizes, and viewpoints. How does the brain rapidly learn and recognize objects while scanning a scene with eye movements, without causing a combinatorial explosion in the number of cells that are needed? How does the brain avoid the problem of erroneously classifying parts of different objects together at the same or different positions in a visual scene? In monkeys and humans, a key area for such invariant object category learning and recognition is the inferotemporal cortex (IT). A neural model is proposed to explain how spatial and object attention coordinate the ability of IT to learn invariant category representations of objects that are seen at multiple positions, sizes, and viewpoints. The model clarifies how interactions within a hierarchy of processing stages in the visual brain accomplish this. These stages include the retina, lateral geniculate nucleus, and cortical areas V1, V2, V4, and IT in the brain's What cortical stream, as they interact with spatial attention processes within the parietal cortex of the Where cortical stream. The model builds upon the ARTSCAN model, which proposed how view-invariant object representations are generated. The positional ARTSCAN (pARTSCAN) model proposes how the following additional processes in the What cortical processing stream also enable position-invariant object representations to be learned: IT cells with persistent activity, and a combination of normalizing object category competition and a view-to-object learning law which together ensure that unambiguous views have a larger effect on object recognition than ambiguous views. The model explains how such invariant learning can be fooled when monkeys, or other primates, are presented with an object that is swapped with another object during eye movements to foveate the original object. The swapping procedure is

  2. Current Trends in Intraoperative Optical Imaging for Functional Brain Mapping and Delineation of Lesions of Language Cortex

    Science.gov (United States)

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

    2009-01-01

    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. PMID:18786643

  3. Neurotransmitters and neuropeptides in depression

    NARCIS (Netherlands)

    Bao, A.-M.; Ruhé, H. G.; Gao, S.-F.; Swaab, D. F.

    2012-01-01

    There are no specific structural neuropathological hallmarks found in the brain of patients with mood disorders. The described alterations confirm, however, a neurodevelopmental underpinning, which is in agreement with the genetic and developmental risk factors. The effect of developmental sequelae

  4. Involvement of the anterior cingulate cortex in time-based prospective memory task monitoring: An EEG analysis of brain sources using Independent Component and Measure Projection Analysis.

    Directory of Open Access Journals (Sweden)

    Gabriela Cruz

    Full Text Available Time-based prospective memory (PM, remembering to do something at a particular moment in the future, is considered to depend upon self-initiated strategic monitoring, involving a retrieval mode (sustained maintenance of the intention plus target checking (intermittent time checks. The present experiment was designed to explore what brain regions and brain activity are associated with these components of strategic monitoring in time-based PM tasks.24 participants were asked to reset a clock every four minutes, while performing a foreground ongoing word categorisation task. EEG activity was recorded and data were decomposed into source-resolved activity using Independent Component Analysis. Common brain regions across participants, associated with retrieval mode and target checking, were found using Measure Projection Analysis.Participants decreased their performance on the ongoing task when concurrently performed with the time-based PM task, reflecting an active retrieval mode that relied on withdrawal of limited resources from the ongoing task. Brain activity, with its source in or near the anterior cingulate cortex (ACC, showed changes associated with an active retrieval mode including greater negative ERP deflections, decreased theta synchronization, and increased alpha suppression for events locked to the ongoing task while maintaining a time-based intention. Activity in the ACC was also associated with time-checks and found consistently across participants; however, we did not find an association with time perception processing per se.The involvement of the ACC in both aspects of time-based PM monitoring may be related to different functions that have been attributed to it: strategic control of attention during the retrieval mode (distributing attentional resources between the ongoing task and the time-based task and anticipatory/decision making processing associated with clock-checks.

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

    International Nuclear Information System (INIS)

    Tsirulnikov, Kirill; Abuladze, Natalia; Bragin, Anatol; Faull, Kym; Cascio, Duilio; Damoiseaux, Robert; Schibler, Matthew J.; Pushkin, Alexander

    2012-01-01

    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.

  6. Fluoro-Jade and TUNEL staining as useful tools to identify ischemic brain damage following moderate extradural compression of sensorimotor cortex.

    Science.gov (United States)

    Kundrotiene, Jurgita; Wägner, Anna; Liljequist, Sture

    2004-01-01

    Cerebral ischemia was produced by moderate compression for 30 min of a specific brain area in the sensorimotor cortex of Sprague-Dawley rats. On day 1, that is 24 h after the transient sensorimotor compression, ischemia-exposed animals displayed a marked focal neurological deficit documented as impaired beam walking performance. This functional disturbance was mainly due to contralateral fore- and hind-limb paresis. As assessed by daily beam walking tests it was shown that there was a spontaneous recovery of motor functions over a period of five to seven days after the ischemic event. Using histopathological analysis (Nissl staining) we have previously reported that the present experimental paradigm does not produce pannecrosis (tissue cavitation) despite the highly reproducible focal neurological deficit. We now show how staining with fluorescent markers for neuronal death, that is Fluoro-Jade and TUNEL, respectively, identifies regional patterns of selective neuronal death. These observations add further support to the working hypothesis that the brain damage caused by cortical compression-induced ischemia consists of scattered, degenerating neurons in specific brain regions. Postsurgical administration of the AMPA receptor specific antagonist, LY326325 (30 mg/kg; i.p., 70 min after compression), not only improved beam walking performance on day 1 to 3, respectively but also significantly reduced the number of Fluoro-Jade stained neurons on day 5. These results suggest that enhanced AMPA/glutamate receptor activity is at least partially responsible for the ischemia-produced brain damage detected by the fluorescent marker Fluoro-Jade.

  7. Functional recovery after injury of motor cortex in rats: effects of rehabilitation and stem cell transplantation in a traumatic brain injury model of cortical resection.

    Science.gov (United States)

    Lee, Do-Hun; Lee, Ji Yeoun; Oh, Byung-Mo; Phi, Ji Hoon; Kim, Seung-Ki; Bang, Moon Suk; Kim, Seung U; Wang, Kyu-Chang

    2013-03-01

    Experimental studies and clinical trials designed to help patients recover from various brain injuries, such as stroke or trauma, have been attempted. Rehabilitation has shown reliable, positive clinical outcome in patients with various brain injuries. Transplantation of exogenous neural stem cells (NSCs) to repair the injured brain is a potential tool to help patient recovery. This study aimed to evaluate the therapeutic efficacy of a combination therapy consisting of rehabilitation and NSC transplantation compared to using only one modality. A model of motor cortex resection in rats was used to create brain injury in order to obtain consistent and prolonged functional deficits. The therapeutic results were evaluated using three methods during an 8-week period with a behavioral test, motor-evoked potential (MEP) measurement, and measurement of the degree of endogenous NSC production. All three treatment groups showed the effects of treatment in the behavioral test, although the NSC transplantation alone group (CN) exhibited slightly worse results than the rehabilitation alone group (CR) or the combination therapy group (CNR). The latency on MEP was shortened to a similar extent in all three groups compared to the untreated group (CO). However, the enhancement of endogenous NSC proliferation was dramatically reduced in the CN group compared not only to the CR and CNR groups but also to the CO group. The CR and CNR groups seemed to prolong the duration of endogenous NSC proliferation compared to the untreated group. A combination of rehabilitation and NSC transplantation appears to induce treatment outcomes that are similar to rehabilitation alone. Further studies are needed to evaluate the electrophysiological outcome of recovery and the possible effect of prolonging endogenous NSC proliferation in response to NSC transplantation and rehabilitation.

  8. Myotropic activity and immunolocalization of selected neuropeptides of the burying beetle Nicrophorus vespilloides (Coleoptera: Silphidae).

    Science.gov (United States)

    Urbański, Arkadiusz; Lubawy, Jan; Marciniak, Paweł; Rosiński, Grzegorz

    2018-01-15

    Burying beetles (Nicrophorus sp.) are necrophagous insects with developed parental care. Genome of Nicrophorus vespilloides has been recently sequenced, which makes them interesting model organism in behavioral ecology. However, we know very little about their physiology, including the functioning of their neuroendocrine system. In this study, one of the physiological activities of proctolin, myosuppressin (Nicve-MS), myoinhibitory peptide (Trica-MIP-5) and the short neuropeptide F (Nicve-sNPF) in N. vespilloides have been investigated. The tested neuropeptides were myoactive on N. vespilloides hindgut. After application of the proctolin increased hindgut contraction frequency was observed (EC 50 value was 5.47 × 10 -8 mol/L). The other tested neuropeptides led to inhibition of N. vespilloides hindgut contractions (Nicve-MS: IC 50 = 5.20 × 10 -5 mol/L; Trica-MIP-5: IC 50 = 5.95 × 10 -6 mol/L; Nicve-sNPF: IC 50 = 4.08 × 10 -5 mol/L). Moreover, the tested neuropeptides were immunolocalized in the nervous system of N. vespilloides. Neurons containing sNPF and MIP in brain and ventral nerve cord (VNC) were identified. Proctolin-immunolabeled neurons only in VNC were observed. Moreover, MIP-immunolabeled varicosities and fibers in retrocerebral complex were observed. In addition, our results have been supplemented with alignments of amino acid sequences of these neuropeptides in beetle species. This alignment analysis clearly showed amino acid sequence similarities between neuropeptides. Moreover, this allowed to deduce amino acid sequence of N. vespilloides proctolin (RYLPTa), Nicve-MS (QDVDHVFLRFa) and six isoforms of Nicve-MIP (Nicve-MIP-1-DWNRNLHSWa; Nicve-MIP-2-AWQNLQGGWa; Nicve-MIP-3-AWQNLQGGWa; Nicve-MIP-4-AWKNLNNAGWa; Nicve-MIP-5-SEWGNFRGSWa; Nicve-MIP-6- DPAWTNLKGIWa; and Nicve-sNPF-SGRSPSLRLRFa). © 2018 Institute of Zoology, Chinese Academy of Sciences.

  9. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Expression of glial fibrillar acidic protein in the sensorimotor cortex of the cerebral hemispheres in the modeling of transient ischemia against the background of previous sensitization by brain antigen and immunocorrection

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    L. M. Yaremenko

    2017-12-01

    Full Text Available Aim. In order to analyze the dynamics of expression of glial fibrillar acidic protein in the sensorimotor cortex of the large hemispheres in the simulation of transient ischemia against the background of previous sensitization by brain antigen and immunocorrection. Materials and methods. The study is conducted on 185 male mature white rats from Wistar line weighing 260-290 g, in which the damage of the brain was modulated. The brain for study was taken on the 1st, 3rd, 10th, 30th and 90th days after the start of the experiment. The histological, immunohistochemical, morphometric and statistical methods were used. Results. Observations have shown that sensitization by the brain antigen causes neurodegenerative changes in the sensorimotor cortex and a moderate increase in the number of GFAP+-gliocytes, which is gradually increasing. The discirculatory changes that occurred with PO and BCA against the background of previous sensitization practically do not lead to changes in the number of GFAP+-cells. Against the background of sensitization by brain antigen, brain ischemia leads to an increase in the number of gliocytes that are GFAP labeled. In the affected hemisphere, their number reaches a maximum in the end of the acute period of ischemia, after which it decreases. But even in 3 months after transient vascular lesion, there are almost twice as many as in conditionally intact rats. This can be a factor that will significantly affect the function of brain regions after a vascular accident. The increase in the number of GFAP+-gliocytes in the contralateral hemisphere allows us to speak about a certain systemic response of astrocytic glia after ischemic trauma. An early reaction to increase of the number of labeled astrocytes just a day after ischemic attack suggests that some of this type of gliocytes does not expresses GFAP under normal conditions. The action of Imunofan in MEAs results in a less significant decrease in manifestations of

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

    International Nuclear Information System (INIS)

    Nomura, S.; Enna, S.J.

    1986-01-01

    Tricyclic antidepressants (TCAs) have anticholinergic and α-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 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 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 α 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

  12. Emerging functions for neuropeptide Y5 receptors

    NARCIS (Netherlands)

    Bischoff, A.; Michel, M. C.

    1999-01-01

    The Y5 subtype of neuropeptide Y (NPY) receptors has raised considerable interest as a mediator of NPY-stimulated food intake, but with the advent of recent data, this hypothesis has come into question. Moreover, Y5 receptor-selective drugs might not be specific for food intake because additional

  13. Spatial structure of neuropeptide allatostatin-4

    International Nuclear Information System (INIS)

    Veliyeva, L.I.; Aliyev, E.Z.

    2011-01-01

    By method of conformational analysis there was determined the spatial structure of neuropeptide allatostatin-4 belonging to allatostatins family. On the basic of value of intramolecular conformational energy calculation was conducted quantitative assessment of the stability of molecule's possible conformational status in dipolar medium terms

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

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    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

  15. The Multiple Correspondence Analysis Method and Brain Functional Connectivity: Its Application to the Study of the Non-linear Relationships of Motor Cortex and Basal Ganglia.

    Science.gov (United States)

    Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Rodriguez, Manuel

    2017-01-01

    The complexity of basal ganglia (BG) interactions is often condensed into simple models mainly based on animal data and that present BG in closed-loop cortico-subcortical circuits of excitatory/inhibitory pathways which analyze the incoming cortical data and return the processed information to the cortex. This study was aimed at identifying functional relationships in the BG motor-loop of 24 healthy-subjects who provided written, informed consent and whose BOLD-activity was recorded by MRI methods. The analysis of the functional interaction between these centers by correlation techniques and multiple linear regression showed non-linear relationships which cannot be suitably addressed with these methods. The multiple correspondence analysis (MCA), an unsupervised multivariable procedure which can identify non-linear interactions, was used to study the functional connectivity of BG when subjects were at rest. Linear methods showed different functional interactions expected according to current BG models. MCA showed additional functional interactions which were not evident when using lineal methods. Seven functional configurations of BG were identified with MCA, two involving the primary motor and somatosensory cortex, one involving the deepest BG (external-internal globus pallidum, subthalamic nucleus and substantia nigral), one with the input-output BG centers (putamen and motor thalamus), two linking the input-output centers with other BG (external pallidum and subthalamic nucleus), and one linking the external pallidum and the substantia nigral. The results provide evidence that the non-linear MCA and linear methods are complementary and should be best used in conjunction to more fully understand the nature of functional connectivity of brain centers.

  16. Radioautographic localization of neuropeptide receptors in central nervous system

    International Nuclear Information System (INIS)

    Rostene, W.; Besson, J.; Broer, Y.

    1985-01-01

    The first step of any physiological effect of a neuropeptide (NP) is its recognition by specific receptor sites. The very organization of the central nervous system (CNS) does not permit a precise localization of these binding sites by conventional binding assays. The aim of the present paper is to describe in detail a recently developed in vitro methodology for the localization, visualization and quantitation of specific binding sites for various NP such as TRH, neurotensin and vasoactive intestinal peptide (VIP) in the rat CNS. The combination of this autoradiographic technique with radioimmunological measurements of NP, reveals that the endogenous distribution of THR, for example, in various brain regions, is not correlated with the presence of its binding sites. In vitro autoradiography may also be used to study the neurotransmitter/neuromodulatory role of NP in the CNS [fr

  17. Interactions of Circadian Rhythmicity, Stress and Orexigenic Neuropeptide Systems: Implications for Food Intake Control

    OpenAIRE

    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 psych...

  18. Radioreceptor assay of opioid peptides in selected canine brain regions

    Energy Technology Data Exchange (ETDEWEB)

    Desiderio, D.M.; Takeshita, H.

    1985-09-01

    A radioreceptor assay using the opioid delta receptor-preferring ligand D-/sup 2/ala, D-/sup 5/leu leucine enkephalin (/sup 3/H-DADL) and the broader-specificity ligand /sup 3/H-etorphine was used to measure five HPLC-purified neuropeptide fractions derived from the peptide-rich fraction of tissue homogenates of nine anatomical regions of the canine brain. The receptoractive peptides studied were methionine enkephalin, alpha-neo-endorphin, dynorphin 1-8, methionine enkephalin-Arg-Phe, and leucine enkephalin. These peptides derive from two larger precursors: proenkephalin A, which contains methionine enkephalin, leucine enkephalin, methionine enkephalin-Arg-Phe; and proenkephalin B, which contains alpha-neo-endorphin and dynorphin 1-8. Receptoractive peptides were measured in the peptide-rich fraction derived from homogenates of canine hypothalamus, pituitary, caudate nucleus, amygdala, hippocampus, mid-brain, thalamus, pons-medulla, and cortex.

  19. Radioreceptor assay of opioid peptides in selected canine brain regions

    International Nuclear Information System (INIS)

    Desiderio, D.M.; Takeshita, H.

    1985-01-01

    A radioreceptor assay using the opioid delta receptor-preferring ligand D- 2 ala, D- 5 leu leucine enkephalin ( 3 H-DADL) and the broader-specificity ligand 3 H-etorphine was used to measure five HPLC-purified neuropeptide fractions derived from the peptide-rich fraction of tissue homogenates of nine anatomical regions of the canine brain. The receptoractive peptides studied were methionine enkephalin, alpha-neo-endorphin, dynorphin 1-8, methionine enkephalin-Arg-Phe, and leucine enkephalin. These peptides derive from two larger precursors: proenkephalin A, which contains methionine enkephalin, leucine enkephalin, methionine enkephalin-Arg-Phe; and proenkephalin B, which contains alpha-neo-endorphin and dynorphin 1-8. Receptoractive peptides were measured in the peptide-rich fraction derived from homogenates of canine hypothalamus, pituitary, caudate nucleus, amygdala, hippocampus, mid-brain, thalamus, pons-medulla, and cortex

  20. Study of neuropeptide distribution in the central nervous system by the combined use of radioimmunoassay with the neuroatomic punch technique

    International Nuclear Information System (INIS)

    Valenca, M.M.; Negro Vilar, A.

    1991-01-01

    In order to demonstrate an experimental method to study neuropeptide distribution in the central nervous system, the content of beta-endorphin present in several brain regions was determined by the combined use of radioimmunoassay with the neuroanatomic punch technique described by Palkovits. (author)

  1. Role of melatonin in mitigating nonylphenol-induced toxicity in frontal cortex and hippocampus of rat brain.

    Science.gov (United States)

    Tabassum, Heena; Ashafaq, Mohammad; Parvez, Suhel; Raisuddin, Sheikh

    2017-03-01

    Nonylphenol (NP), an environmental endocrine disruptor mimics estrogen and is a potential toxicant both under in vitro and in vivo conditions. In this study, the effect of melatonin on NP- induced neurotoxicity and cognitive alteration was investigated in adult male Wistar rats. Melatonin supplementation has been known to protect cells from neurotoxic injury. The animals were divided into three groups namely, control (vehicle) which received olive oil orally and treated rats received NP (25 mg/kg, per os) thrice a week for 45 days while the third group i.e., NP + melatonin, animals were co-administered melatonin (10 mg/kg, i.p.) along with NP. On the 46th day, rats were assessed for anxiety, motor co-ordination, grip strength and cognitive performance using Morris water maze test and then sacrificed for biochemical and histopathological assays in brain tissues. Melatonin improved the behavioral performance in NP exposed group. The results showed that NP significantly decreased the activity of acetylcholine esterase (AchE), monoamine oxidase (MAO) and Na + /K + -ATPase, in rat brain tissue along with other enzymes of antioxidant milieu. The outcome of the study shows that NP, like other persistent endocrine disrupting pollutants, creates a potential risk of cognitive, neurochemical and histopathological perturbations as a result of environmental exposure. Taken together, our study demonstrates that melatonin is protective against NP-induced neurotoxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Sex-specific association between functional neuropeptide S receptor gene (NPSR1) variants and cortisol and central stress responses.

    Science.gov (United States)

    Streit, Fabian; Akdeniz, Ceren; Haddad, Leila; Kumsta, Robert; Entringer, Sonja; Frank, Josef; Yim, Ilona S; Zänkert, Sandra; Witt, Stephanie H; Kirsch, Peter; Rietschel, Marcella; Wüst, Stefan

    2017-02-01

    The brain neuropeptide S (NPS) system has recently generated substantial interest and may be of major relevance for central stress regulation. The NPS receptor (NPSR1) is highly expressed in the limbic system, exogenous NPS exerts pronounced anxiolytic and fear-attenuating effects in rodents and extensive close crosstalk between the NPS system and the hypothalamic-pituitary-adrenal (HPA) axis has been demonstrated. In humans, associations between NPSR1 variants and anxiety and panic disorder, as well as amygdala responsiveness to fear- relevant faces and prefrontal cortex activity in a fear conditioning paradigm have been reported. Moreover, a NPSR1 sequence variant was found to be associated with cortisol stress responses in males. Here, we performed a haplotype-based analysis covering three functional NPSR1 single nucleotide polymorphisms in the promoter (rs2530547), in exon 3 (rs324981) and exon 6 (rs727162) in 277 healthy subjects who were exposed to the Trier Social Stress Test (TSST). A significant sex-specific association with salivary cortisol responses to acute psychosocial stress was detected for the common TTC haplotype 2 (frequency of about 20%). In an additional study using an imaging genetics approach, 65 healthy subjects were exposed to a stress paradigm for scanner environments (“ScanSTRESS”). We found a significant and, again, sex-specific interaction between rs324981 (whose minor T-allele is harbored by haplotype 2) and the neural stress response in a cluster close to the parahippocampal gyrus (whole brain corrected). Moreover, as in the TSST sample, NPSR1 variation was associated with salivary cortisol responses (on a trend level) in a sex-specific way. In summary, our preliminary findings in two independent cohorts exposed to different stress paradigms suggest that the NPS system significantly influences acute stress responses and that sequence variation in NPSR1 may contribute to sex differences in stress regulation. Copyright © 2016

  3. Salicylate-Induced Suppression of Electrically Driven Activity in Brain Slices from the Auditory Cortex of Aging Mice

    Directory of Open Access Journals (Sweden)

    Minoru Namikawa

    2017-12-01

    Full Text Available The prevalence of tinnitus is known to increase with age. The age-dependent mechanisms of tinnitus may have important implications for the development of new therapeutic treatments. High doses of salicylate can be used experimentally to induce transient tinnitus and hearing loss. Although accumulating evidence indicates that salicylate induces tinnitus by directly targeting neurons in the peripheral and central auditory systems, the precise effect of salicylate on neural networks in the auditory cortex (AC is unknown. Here, we examined salicylate-induced changes in stimulus-driven laminar responses of AC slices with salicylate superfusion in young and aged senescence-accelerated-prone (SAMP and -resistant (SAMR mice. Of the two strains, SAMP1 is known to be a more suitable model of presbycusis. We recorded stimulus-driven laminar local field potential (LFP responses at multi sites in AC slice preparations. We found that for all AC slices in the two strains, salicylate always reduced stimulus-driven LFP responses in all layers. However, for the amplitudes of the LFP responses, the two senescence-accelerated mice (SAM strains showed different laminar properties between the pre- and post-salicylate conditions, reflecting strain-related differences in local circuits. As for the relationships between auditory brainstem response (ABR thresholds and the LFP amplitude ratios in the pre- vs. post-salicylate condition, we found negative correlations in layers 2/3 and 4 for both older strains, and in layer 5 (L5 in older SAMR1. In contrast, the GABAergic agonist muscimol (MSC led to positive correlations between ABR thresholds and LFP amplitude ratios in the pre- vs. post-MSC condition in younger SAM mice from both strains. Further, in younger mice, salicylate decreased the firing rate in AC L4 pyramidal neurons. Thus, salicylate can directly reduce neural excitability of L4 pyramidal neurons and thereby influence AC neural circuit activity. That we

  4. Structural brain correlates of executive engagement in working memory: children's inter-individual differences are reflected in the anterior insular cortex.

    Science.gov (United States)

    Rossi, Sandrine; Lubin, Amélie; Simon, Grégory; Lanoë, Céline; Poirel, Nicolas; Cachia, Arnaud; Pineau, Arlette; Houdé, Olivier

    2013-06-01

    Although the development of executive functions has been extensively investigated at a neurofunctional level, studies of the structural relationships between executive functions and brain anatomy are still scarce. Based on our previous meta-analysis of functional neuroimaging studies examining executive functions in children (Houdé, Rossi, Lubin, and Joliot, (2010). Developmental Science, 13, 876-885), we investigated six a priori regions of interest: the left anterior insular cortex (AIC), the left and the right supplementary motor areas, the right middle and superior frontal gyri, and the left precentral gyrus. Structural magnetic resonance imaging scans were acquired from 22 to 10-year-old children. Local gray matter volumes, assessed automatically using a standard voxel-based morphometry approach, were correlated with executive and storage working memory capacities evaluated using backward and forward digit span tasks, respectively. We found an association between smaller gray matter volume--i.e., an index of neural maturation--in the left AIC and high backward memory span while gray matter volumes in the a priori selected regions of interest were not linked with forward memory span. These results were corroborated by a whole-brain a priori free analysis that revealed a significant negative correlation in the frontal and prefrontal regions, including the left AIC, with the backward memory span, and in the right inferior parietal lobe, with the forward memory span. Taken together, these results suggest a distinct and specific association between regional gray matter volume and the executive component vs. the storage component of working memory. Moreover, they support a key role for the AIC in the executive network of children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Brain-derived neurotrophic factor (BDNF) in the rostral anterior cingulate cortex (rACC) contributes to neuropathic spontaneous pain-related aversion via NR2B receptors.

    Science.gov (United States)

    Zhang, Le; Wang, Gongming; Ma, Jinben; Liu, Chengxiao; Liu, Xijiang; Zhan, Yufeng; Zhang, Mengyuan

    2016-10-01

    The rostral anterior cingulate cortex (rACC) plays an important role in pain affect. Previous investigations have reported that the rACC mediates the negative affective component of inflammatory pain and contributed to the aversive state of nerve injury-induced neuropathic pain. Brain-derived neurotrophic factor (BDNF), an activity-dependent neuromodulator in the adult brain, is believed to play a role in the development and maintenance of inflammatory and neuropathic pain in the spinal cord. However, whether and how BDNF in the rACC regulates pain-related aversion due to peripheral nerve injury is largely unknown. Behaviorally, using conditioned place preference (CPP) training in rats, which is thought to reveal spontaneous pain-related aversion, we found that CPP was acquired following spinal clonidine in rats with partial sciatic nerve transection. Importantly, BDNF was upregulated within the rACC in of rats with nerve injury and enhanced the CPP acquisition, while a local injection of a BDNF-tropomyosin receptor kinase B (TrkB) antagonist into the rACC completely blocked this process. Finally, we demonstrated that the BDNF/TrkB pathway exerted its function by activating the NR2B receptor, which is widely accepted to be a crucial factor contributing to pain affect. In conclusion, our results demonstrate that the BDNF/TrkB-mediated signaling pathway in the rACC is involved in the development of neuropathic spontaneous pain-related aversion and that this process is dependent upon activation of NR2B receptors. These findings suggest that suppression of the BDNF-related signaling pathway in the rACC may provide a novel strategy to overcome pain-related aversion. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. 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.

  7. 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.

  8. 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.

  9. Motor cortex stimulation(MCS) for intractable complex regional pain syndrome (CRPS) type II: PSM analysis of Tc-99m ECD brain perfusion SPECT

    International Nuclear Information System (INIS)

    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.

    2001-01-01

    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

  10. Mechanisms of L-Triiodothyronine-Induced Inhibition of Synaptosomal Na+-K+-ATPase Activity in Young Adult Rat Brain Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Pradip K. Sarkar

    2013-01-01

    Full Text Available The role of thyroid hormones (TH in the normal functioning of adult mammalian brain is unclear. Our studies have identified synaptosomal Na+-K+-ATPase as a TH-responsive physiological parameter in adult rat cerebral cortex. L-triiodothyronine (T3 and L-thyroxine (T4 both inhibited Na+-K+-ATPase activity (but not Mg2+-ATPase activity in similar dose-dependent fashions, while other metabolites of TH were less effective. Although both T3 and the β-adrenergic agonist isoproterenol inhibited Na+-K+-ATPase activity in cerebrocortical synaptosomes in similar ways, the β-adrenergic receptor blocker propranolol did not counteract the effect of T3. Instead, propranolol further inhibited Na+-K+-ATPase activity in a dose-dependent manner, suggesting that the effect of T3 on synaptosomal Na+-K+-ATPase activity was independent of β-adrenergic receptor activation. The effect of T3 on synaptosomal Na+-K+-ATPase activity was inhibited by the α2-adrenergic agonist clonidine and by glutamate. Notably, both clonidine and glutamate activate Gi-proteins of the membrane second messenger system, suggesting a potential mechanism for the inhibition of the effects of TH. In this paper, we provide support for a nongenomic mechanism of action of TH in a neuronal membrane-related energy-linked process for signal transduction in the adult condition.

  11. 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.

  12. Neuropeptides in the desert ant Cataglyphis fortis: Mass spectrometric analysis, localization, and age-related changes.

    Science.gov (United States)

    Schmitt, Franziska; Vanselow, Jens T; Schlosser, Andreas; Wegener, Christian; Rössler, Wolfgang

    2017-03-01

    Cataglyphis desert ants exhibit an age-related polyethism, with ants performing tasks in the dark nest for the first ∼4 weeks of their adult life before they switch to visually based long-distance navigation to forage. Although behavioral and sensory aspects of this transition have been studied, the internal factors triggering the behavioral changes are largely unknown. We suggest the neuropeptide families allatostatin A (AstA), allatotropin (AT), short neuropeptide F (sNPF), and tachykinin (TK) as potential candidates. Based on a neuropeptidomic analysis in Camponotus floridanus, nano-LC-ESI MS/MS was used to identify these neuropeptides biochemically in Cataglyphis fortis. Furthermore, we show that all identified peptide families are present in the central brain and ventral ganglia of C. fortis whereas in the retrocerebral complex only sNPF could be detected. Immunofluorescence staining against AstA, AT, and TK in the brain revealed arborizations of AstA- and TK-positive neurons in primary sensory processing centers and higher order integration centers, whereas AT immunoreactivity was restricted to the central complex, the antennal mechanosensory and motor center, and the protocerebrum. For artificially dark-kept ants, we found that TK distribution changed markedly in the central complex from days 1 and 7 to day 14 after eclosion. Based on functional studies in Drosophila, this age-related variation of TK is suggestive of a modulatory role in locomotion behavior in C. fortis. We conclude that the general distribution and age-related changes in neuropeptides indicate a modulatory role in sensory input regions and higher order processing centers in the desert ant brain. J. Comp. Neurol. 525:901-918, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Alterations in neuropeptides in aging and disease. Pathophysiology and potential for clinical intervention.

    Science.gov (United States)

    Leake, A; Ferrier, I N

    1993-01-01

    Marked specific and selective changes in the levels of some neuropeptides in age-related diseases, such as senile dementia of the Alzheimer (SDAT) or Lewy body (SDLT) types, Parkinson's disease, Huntington's disease and major depressive disorder, versus normal aging have been noted. However, the levels of most neuropeptides are normal. The only 2 peptides consistently altered in SDAT are somatostatin and corticotrophin-releasing hormone both of which are reduced. In Huntington's disease, the level of substance P in the basal ganglia is reduced suggesting a preferential vulnerability of spiny neurones in this disease. In Parkinson's disease, substance P is attenuated in the basal ganglia while somatostatin is reduced in the neocortex. These and other results suggest that substance P deficits are related to movement disorders while somatostatin deficits are related to cognitive impairment. SDLT is a type of dementia with features common to both SDAT and Parkinson's disease, although the changes in neuropeptides suggest that neurochemically the disease is more closely related to SDAT. In major depressive disorder, the level of corticotrophin-releasing hormone is reduced while there is a reciprocal increase in corticotrophin-releasing hormone receptors suggesting that the neurones remain functional. Potential clinical intervention has been limited by problems such as poor penetration of agents into the brain and the short half-lives of neuropeptide agonists and antagonists. However, some currently available agents may act, at least in part, through modulation of neuropeptide pathways, e.g. carbamazepine and alprazolam both modulate the corticotrophin-releasing hormone system in animals, and both have clinically proven antidepressant activity.

  14. Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans.

    Science.gov (United States)

    Nomura, Sadahiro; Fujii, Masami; Inoue, Takao; He, Yeting; Maruta, Yuichi; Koizumi, Hiroyasu; Suehiro, Eiichi; Imoto, Hirochika; Ishihara, Hideyuki; Oka, Fumiaki; Matsumoto, Mishiya; Owada, Yuji; Yamakawa, Takeshi; Suzuki, Michiyasu

    2014-05-01

    Recently, focal brain cooling (FBC) was proposed as a method for treating refractory epilepsy. However, the precise influence of cooling on the molecular basis of epilepsy has not been elucidated. Thus the aim of this study was to assess the effect of FBC on glutamate (Glu) concentration, cerebral blood flow (CBF), and glucose metabolism in patients with intractable epilepsy. Nine patients underwent FBC at 15°C for 30 min prior to cortical resection (n = 6) or hippocampectomy (n = 3). Measurement of metabolites and CBF, as well as electrocorticography (ECoG), was performed. Epileptic discharge (ED), as observed by ECoG, disappeared in the cooling period and reappeared in the rewarming period. Glu concentrations were high during the precooling period and were reduced to 51.2% during the cooling period (p = 0.025). Glycerol levels showed a similar decrease (p = 0.028). Lactate concentration was high during the precooling period and was reduced during the cooling period (21.3% decrease; p = 0.005). Glucose and pyruvate levels were maintained throughout the procedure. Changes in CBF were parallel to those observed by ECoG. FBC reduced EDs and concentrations of Glu and glycerol. This demonstrates the neuroprotective effect of FBC. Our findings confirm that FBC is a reasonable and optimal treatment option for patients with intractable epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  15. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation.

    Science.gov (United States)

    Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

    2014-01-01

    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.

  16. 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.

  17. 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.

  18. 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.

  19. A Multifaceted Mass Spectrometric Method to Probe Feeding Related Neuropeptide Changes in Callinectes sapidus and Carcinus maenas

    Science.gov (United States)

    Zhang, Yuzhuo; DeLaney, Kellen; Hui, Limei; Wang, Junhua; Sturm, Robert M.; Li, Lingjun

    2018-05-01

    Food intake is regulated by various neuromodulators, including numerous neuropeptides. However, it remains elusive at the molecular and cellular level as to how these important chemicals regulate internal processes and which regions of the neuronal organs are responsible for regulating the behavior. Here we report a comparative neuropeptidomic analysis of the brain and pericardial organ (PO) in response to feeding in two well-studied crustacean physiology model organisms, Callinectes sapidus and Carcinus maenas, using mass spectrometry (MS) techniques. A multifaceted MS-based approach has been developed to obtain complementary information on the expression changes of a large array of neuropeptides in the brain and PO. The method employs stable isotope labeling of brain and PO extracts for relative MS quantitation, capillary electrophoresis (CE)-MS for fractionation and high-specificity analysis, and mass spectrometric imaging (MSI) for in-situ molecular mapping of peptides. A number of neuropeptides, including RFamides, B-type allatostatins (AST-B), RYamides, and orcokinins exhibit significant changes in abundance after feeding in this investigation. Peptides from the AST-B family found in PO tissue were shown to have both altered expression and localization changes after feeding, indicating that they may be a class of vital neuropeptide regulators involved in feeding behavior. [Figure not available: see fulltext.

  20. Study of the Neuropeptide Function in Parkinson’s Disease Using the 6-Hydroxydopamine Model of Experimental Hemiparkinsonism

    Directory of Open Access Journals (Sweden)

    I. Banegas

    2017-11-01

    Full Text Available Parkinson’s disease, one of the most common neurodegenerative diseases, characterized by unilateral brain dopamine damage in its initial stages, remains unknown in many respects. It is especially necessary to improve the early diagnosis and, in order to improve the treatment, to go thoroughly into the knowledge of its pathophysiology. To do this, it is essential to perform studies in appropriate animal models of the disease. One of those is generated by the unilateral intracerebral administration of the neurotoxic 6-hydroxydopamine that produces clear asymmetrical cerebral dopamine depletion. Currently the neuronal coexistence of several neurotransmitters is obvious. Particularly interesting is the coexistence of dopamine with various neuropeptides. If the neuronal content of dopamine is asymmetrically altered in the early stages of the Parkinson’s disease, the coexisting neuropeptides may also be asymmetrically altered. Therefore, their study is important to appropriately understand the pathogenesis of the Parkinson’s disease. The function of the neuropeptides can be studied through their metabolism by neuropeptidases whose activity reflects the functional status of their endogenous substrates as well as the one of the peptides resulting from their hydrolysis. Here we review the 6-hydroxydopamine model of experimental hemiparkinsonism as an appropriate model to study the initial asymmetric stages of the disease. In particular, we analyze the consequences of unilateral brain dopamine depletions on the functionality of brain neuropeptides through the study of the activity of cerebral neuropeptidases.

  1. A Multifaceted Mass Spectrometric Method to Probe Feeding Related Neuropeptide Changes in Callinectes sapidus and Carcinus maenas

    Science.gov (United States)

    Zhang, Yuzhuo; DeLaney, Kellen; Hui, Limei; Wang, Junhua; Sturm, Robert M.; Li, Lingjun

    2018-02-01

    Food intake is regulated by various neuromodulators, including numerous neuropeptides. However, it remains elusive at the molecular and cellular level as to how these important chemicals regulate internal processes and which regions of the neuronal organs are responsible for regulating the behavior. Here we report a comparative neuropeptidomic analysis of the brain and pericardial organ (PO) in response to feeding in two well-studied crustacean physiology model organisms, Callinectes sapidus and Carcinus maenas, using mass spectrometry (MS) techniques. A multifaceted MS-based approach has been developed to obtain complementary information on the expression changes of a large array of neuropeptides in the brain and PO. The method employs stable isotope labeling of brain and PO extracts for relative MS quantitation, capillary electrophoresis (CE)-MS for fractionation and high-specificity analysis, and mass spectrometric imaging (MSI) for in-situ molecular mapping of peptides. A number of neuropeptides, including RFamides, B-type allatostatins (AST-B), RYamides, and orcokinins exhibit significant changes in abundance after feeding in this investigation. Peptides from the AST-B family found in PO tissue were shown to have both altered expression and localization changes after feeding, indicating that they may be a class of vital neuropeptide regulators involved in feeding behavior. [Figure not available: see fulltext.

  2. Neuropeptide levels in Dercum's disease (adiposis dolorosa

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    H. Brorson

    2012-07-01

    Full Text Available Dercum’s disease (adiposis dolorosa is characterised by adiposity and chronic pain in the adipose tissue. It has been proposed that conditions encompassing chronic pain have altered concentrations of neuropeptides involved in pain transmission. The aim of this investigation was to examine whether patients with Dercum’s disease have abnormal concentrations of different neuropeptides. In cerebrospinal fluid (CSF and in plasma (P from 53 patients with Dercum’s disease substance P-like immunoreactivity (SP-LI, neuropeptide Y-like immunoreactivity (NPY-LI, b-endorphin-like immunoreactivity (b-END-LI, calcitonin gene-related peptidelike immunoreactivity (CGRP-LI, met-enkephalin-like immunoreactivity (m-ENK-LI, vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI, somatostatin (SOM-LI, g2-melanocyte-stimulating hormone-like immunoreactivity (g2-MSH-LI, and dynorphin-like immunoreactivity (DYN-LI were measured. Three of the substances were also measured in a control group. The CSF concentration of SP was statistically significantly lower in the Dercum group than in the control group, whereas NPY-LI and b-END-LI were borderline statistically significantly lower and higher, respectively, in Dercum patients compared to controls. Compared with reference values, CSF-MSH-LI levels were slightly elevated and CSF-NPY-LI levels were slightly lowered in the Dercum group. The other substances in both CSF and plasma were within the reference values with a high degree of statistical significance. In conclusion, altered levels of neuropeptides that have previously been seen in different pain conditions cannot clearly be demonstrated in Dercum’s disease.

  3. Plasma Membrane Density of GABA(B)-R1a, GABA(B)-R1b, GABA-R2 and Trimeric G-proteins in the Course of Postnatal Development of Rat Brain Cortex

    Czech Academy of Sciences Publication Activity Database

    Dlouhá, Kateřina; Kagan, Dmytro; Roubalová, Lenka; Ujčíková, Hana; Svoboda, Petr

    2013-01-01

    Roč. 62, č. 5 (2013), s. 547-559 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP207/12/0919; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : GABAB-receptors * postnatal development * rat brain cortex * G-proteins * Na, K- ATPase Subject RIV: CE - Biochemistry Impact factor: 1.487, year: 2013

  4. Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

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    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.

  5. Brain-Derived Neurotrophic Factor – A Major Player in Stimulation-Induced Homeostatic Metaplasticity of Human Motor Cortex?

    Science.gov (United States)

    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 val66met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val66met 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 val66met (n = 12) and val66val (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, val66met carriers and val66val 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 val66met polymorphism, our results do not support the notion that the BDNF val66met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND. PMID:23469118

  6. 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.

  7. Rapid and long-term induction of effector immediate early genes (BDNF, Neuritin and Arc) in peri-infarct cortex and dentate gyrus after ischemic injury in rat brain

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Teilum, Maria; Wieloch, Tadeusz

    2007-01-01

    including cerebral cortex and hippocampus. Brain-derived neurotrophic factor (BDNF), Neuritin and Activity-regulated cytoskeleton-associated protein (Arc) belong to a subgroup of immediate early genes implicated in synaptic plasticity known as effector immediate early genes. Here, we investigated...... at 0-6 h of reperfusion for Neuritin and 0-12 h of reperfusion for Arc while BDNF was induced 0-9 h of reperfusion. Our study demonstrates a rapid and long-term activation of effector immediate early genes in distinct brain areas following ischemic injury in rat. Effector gene activation may be part...

  8. Reducing the harm of stress: medications to rescue the prefrontal cortex and overcome bad habits: the science of stress: focus on the brain, breaking bad habits, and chronic disease.

    Science.gov (United States)

    Jin, Lu E

    2011-12-01

    Our brain is sensitive to stress. Both acute and chronic stress cause cognitive deficits and induce chronic disorders such as drug addiction. In a June 2011 conference at Yale entitled "The Science of Stress: Focus on the Brain, Breaking Bad Habits, and Chronic Disease," Drs. Amy Arnsten and Sherry Mckee discussed the roles of prefrontal cortex in the treatment of stress impairments and addiction. Medications to strengthen the prefrontal function, such as prazosin and guanfacine, may reduce the harm of stress and help overcome smoking and alcohol abuse.

  9. The possible role of neuropeptide Y after spontaneous subarachnoid hemorrhage.

    Science.gov (United States)

    Schebesch, Karl-Michael; Brawanski, Alexander; Kagerbauer, Simone Maria; Martin, Jan; Bele, Sylvia; Herbst, Andreas; Feigl, Günther; Stoerr, Eva-Maria; Lohmeier, Anette; Proescholdt, Martin

    2011-08-01

    Neuropeptide Y (NPY), a highly potent vasoconstrictive neuropeptide, is widely expressed in the human brain, regulating vessel diameter and cerebral blood flow. Earlier studies focusing on the possible role of NPY in the context of aneurismal subarachnoid hemorrhage (SAH) and vasospasm have produced conflicting results. However, despite extensive research efforts, the pathophysiological mechanisms underlying the SAH-related vasospasm and delayed cerebral ischemia (DCI) have not been clarified. We, therefore, attempted to investigate the role of NPY in SAH-induced vasospasm in a larger, well documented patient population utilizing modern analytical tools. We focused on the release of the potent vasoconstrictor NPY in cerebrospinal fluid (CSF) and blood, and its correlation to vasospasm and stroke in the early clinical stage. Thirty-seven patients with SAH and a control group consisting of 29 patients were included. Eighteen patients developed stroke, 21 patients met the Doppler sonographical criteria for vasospasm. Twenty-nine patients had aneurysms of the anterior circulation and four patients of the posterior circulation. All patients had ventricular drainage inserted and an arterial catheter. Blood and CSF were drawn daily for NPY analysis during a 10-day interval. The levels of NPY in CSF and plasma were significantly higher after SAH than in the control group (p = 0.001). The vasospasm group showed NPY levels in CSF which continuously ranged above the NPY levels of the non-vasospasm group (p = 0.001). Patients with stroke caused by vasospasm had significantly higher levels of NPY (p = 0.001). NPY is released excessively into blood and CSF following SAH. Patients with cerebral infarction caused by vasospasm had significantly higher levels of NPY. Our results indicate a certain role for NPY in the pathophysiology of vasospasm due to SAH and justify further studies in this area of research.

  10. 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.

  11. 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

  12. Fluorescent ligands for studying neuropeptide receptors by confocal microscopy

    Directory of Open Access Journals (Sweden)

    A. Beaudet

    1998-11-01

    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.

  13. Brain perfusion ratios by 99mTc HMPAO SPECT utilizing a mean value of the visual cortex to the cerebellum ratio derived from normal subjects

    International Nuclear Information System (INIS)

    Sanchez Catasus, C.; Rodriguez, R.; Cisnero, M.; Palmero, R.; Diaz, O.; Aguila, A.

    2002-01-01

    Aim: Previous results shows that the cerebellum (CER) is the best reference to calculate relative indexes of perfusion (IP) by brain SPECT. However, it can not be used on patients with bilateral cerebellar hypoperfusion. In such cases visual cortex (VC) or an average of the whole brain activity is recommended (WB). VC and WB are less reliable than CER, making it difficult to compare SPECT scans that have been normalized with different values. Materials and Methods: To overcome this difficulty, we developed a method to calculate IP utilizing a reference value defined as (VC / ), where is the mean value of the VC/CER ratio derived from a normal database which was assumed to be constant. We called the value VC/ the 'Pseudocerebellum' (PCER). For clinical validation, we first tested statistically the VC/CER ratio on a group of 60 [ 99m Tc]-HMPAO SPECT scans of 20 normal subjects and 40 neurological patients with positive SPECT but without involvement of VC and CER. To demonstrate that IP PCER approx. IP CER , we calculated the mean value of the absolute differences CER - IP PCER vertical bar> on two groups of scans from subjects without involvement of VC and CER: 10 normal subjects (GI); and 40 patients (GII). Finally, using an indirect procedure the method was tested on a third group of SPECT scans of 30 patients with bilateral cerebellar hypoperfusion (G III). Results: The VC/CER ratio was approximately constant with gender and age at a 95% confidence level; CER - IP PCER vertical bar> was 1.22%±0.35 and 1.20%±0.42 for GI and GII, respectively. This is less than the within-subject replicability of the HMPAO SPECT studies; and thus demonstrated by an indirect approach that IP PCER is a valid procedure by which to evaluate relative perfusion on patients with bilateral cerebellar hypoperfusion and quantitatively comparable to using CER as reference region. Conclusion: The VC/CER ratio has very little inter-subject variability in individuals where these regions are not

  14. Tributyltin induces oxidative damage, inflammation and apoptosis via disturbance in blood-brain barrier and metal homeostasis in cerebral cortex of rat brain: an in vivo and in vitro study.

    Science.gov (United States)

    Mitra, Sumonto; Gera, Ruchi; Siddiqui, Waseem A; Khandelwal, Shashi

    2013-08-09

    Tributyltin (TBT), a member of the organotin family, is primarily used for its biocidal activity. Persistent environmental levels of TBT pose threat to the ecosystem. Since neurotoxic influence of TBT remains elusive, we therefore, studied its effect on cerebral cortex of male Wistar rats. A single oral dose of Tributyltin-Chloride (TBTC) (10, 20, 30mg/kg) was administered and the animals were sacrificed on day 3 and day 7. Blood-brain barrier permeability remained disrupted significantly till day 7 with all the doses of TBTC. Pro-oxidant metal levels (Fe, Cu) were increased with a concomitant decrease in Zn. ROS generation was substantially raised resulting in oxidative damage (increased protein carbonylation and lipid peroxidation) with marked decline in tissue antioxidant status (GSH/GSSG levels). Protein expression studies indicated astrocyte activation, upregulation of inflammatory molecules (IL-6, Cox-2 and NF-κB) and simultaneous elevation in the apoptotic index (Bax/Bcl2). Neurodegeneration was evident by reduced neurofilament expression and increased calpain cleaved Tau levels. The in-vitro study demonstrated involvement of calcium and signaling molecules (p38), with downstream activation of caspase-3 and -8, and apoptotic cell death was evident by nuclear fragmentation, DNA laddering and Annexin V binding experiments. Ca(2+) inhibitors (BAPTA-AM, EGTA, and RR) and free radical scavengers (NAC and biliprotein [C-PC]) increased cell viability (MTT assay), signifying specific roles of Ca(2+) and ROS. Significance of p38 signaling was evaluated on pro-apoptotic proteins by using SB203580, a selective p38 inhibitor. Our data collectively illustrates that TBTC can disrupt BBB, induce oxidative stress, cause cell death and initiate neurodegeneration in rat brain. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Tributyltin induces oxidative damage, inflammation and apoptosis via disturbance in blood–brain barrier and metal homeostasis in cerebral cortex of rat brain: An in vivo and in vitro study

    International Nuclear Information System (INIS)

    Mitra, Sumonto; Gera, Ruchi; Siddiqui, Waseem A.; Khandelwal, Shashi

    2013-01-01

    Highlights: • Sustainable blood–brain barrier disruption was found by single acute dose of TBTC (up to 1 week). • Imbalance in essential metal homeostasis in the cortical tissue may lead to oxidative stress. • Astroglial activation and inflammation resulted in neuronal loss. • TBTC primarily induced apoptosis as found in in-vitro study via activation of calcium, p38 signaling, ROS and caspases. • Calcium inhibitors and anti-oxidants showed protective efficacy in TBTC induced cell death. - Abstract: Tributyltin (TBT), a member of the organotin family, is primarily used for its biocidal activity. Persistent environmental levels of TBT pose threat to the ecosystem. Since neurotoxic influence of TBT remains elusive, we therefore, studied its effect on cerebral cortex of male Wistar rats. A single oral dose of Tributyltin-Chloride (TBTC) (10, 20, 30 mg/kg) was administered and the animals were sacrificed on day 3 and day 7. Blood–brain barrier permeability remained disrupted significantly till day 7 with all the doses of TBTC. Pro-oxidant metal levels (Fe, Cu) were increased with a concomitant decrease in Zn. ROS generation was substantially raised resulting in oxidative damage (increased protein carbonylation and lipid peroxidation) with marked decline in tissue antioxidant status (GSH/GSSG levels). Protein expression studies indicated astrocyte activation, upregulation of inflammatory molecules (IL-6, Cox-2 and NF-κB) and simultaneous elevation in the apoptotic index (Bax/Bcl2). Neurodegeneration was evident by reduced neurofilament expression and increased calpain cleaved Tau levels. The in-vitro study demonstrated involvement of calcium and signaling molecules (p38), with downstream activation of caspase-3 and -8, and apoptotic cell death was evident by nuclear fragmentation, DNA laddering and Annexin V binding experiments. Ca 2+ inhibitors (BAPTA-AM, EGTA, and RR) and free radical scavengers (NAC and biliprotein [C-PC]) increased cell viability (MTT

  16. 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.

  17. Micellar nanomedicine of human neuropeptide Y.

    Science.gov (United States)

    Kuzmis, Antonina; Lim, Sok Bee; Desai, Esha; Jeon, Eunjung; Lee, Bao-Shiang; Rubinstein, Israel; Onyüksel, Hayat

    2011-08-01

    Human neuropeptide Y (NPY) is an important biologics that regulates a multitude of physiological functions and could be amenable to therapeutic manipulations in certain disease states. However, rapid (within minutes) enzymatic degradation and inactivation of NPY precludes its development as a drug. Accordingly, we determined whether self-association of NPY with biocompatible and biodegradable sterically stabilized phospholipid micelles (SSM) improves its stability and bioactivity. We found that in saline NPY spontaneously aggregates; however, in the presence of SSM it self-associates with the micelles as monomers. Three NPY molecules self-associate with 1 SSM at saturation. This process stabilizes the peptide in α-helix conformation, abrogates its degradation by dipeptidyl peptidase-4 and potentiates NPY-induced inhibition of cAMP elaboration in SK-N-MC cells. Collectively, these data indicate that self-association of NPY with SSM stabilizes and protects the peptide in active monomeric conformation, thereby amplifying its bioactivity in vitro. We propose further development of NPY in SSM as a novel, long-acting nanomedicine. Human neuropeptide Y (NPY) regulates a multitude of physiological functions and could be amenable to therapeutic manipulations, which is currently limited by its short half life. Self-association of NPY with spherically stabilized micelles (SSM) protects and stabilizes the peptide in active monomeric conformation, thereby amplifying its bioactivity in vitro, enabling future therapeutic considerations. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Maps of the Auditory Cortex.

    Science.gov (United States)

    Brewer, Alyssa A; Barton, Brian

    2016-07-08

    One of the fundamental properties of the mammalian brain is that sensory regions of cortex are formed of multiple, functionally specialized cortical field maps (CFMs). Each CFM comprises two orthogonal topographical representations, reflecting two essential aspects of sensory space. In auditory cortex, auditory field maps (AFMs) are defined by the combination of tonotopic gradients, representing the spectral aspects of sound (i.e., tones), with orthogonal periodotopic gradients, representing the temporal aspects of sound (i.e., period or temporal envelope). Converging evidence from cytoarchitectural and neuroimaging measurements underlies the definition of 11 AFMs across core and belt regions of human auditory cortex, with likely homology to those of macaque. On a macrostructural level, AFMs are grouped into cloverleaf clusters, an organizational structure also seen in visual cortex. Future research can now use these AFMs to investigate specific stages of auditory processing, key for understanding behaviors such as speech perception and multimodal sensory integration.

  19. Behavioral Effects of Deep Brain Stimulation of the Anterior Nucleus of Thalamus, Entorhinal Cortex and Fornix in a Rat Model of Alzheimer′s Disease

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    2015-01-01

    Full Text Available 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 of amyloid 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 than ANT 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.

  20. Control of sleep-to-wake transitions via fast amino acid and slow neuropeptide transmission

    International Nuclear Information System (INIS)

    Mosqueiro, Thiago; Lecea, Luis de; 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 on a time scale of several seconds. Evidence from anatomical, electrophysiological and optogenetic experiments has shown that LC neurons receive input from a group of neurons called hypocretin neurons that release a neuropeptide called hypocretin. It is less well known how these two groups of neurons can be coregulated using GABAergic (GABA standing for gamma aminobutyric acid) neurons. As the time scale for GABA A inhibition is several orders of magnitude faster than that for the hypocretin neuropeptide effect, we investigate the limits of circuit activity regulation using a realistic model of neurons. Our investigation shows that GABA A inhibition is insufficient to control the activity levels of the LCs. Although slower forms of GABA A can in principle work, there is not much plausibility due to the low probability of the presence of slow GABA A 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, which exert effects on a similar time scale to 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. (paper)

  1. CEREBRAL CORTEX DAMAGE INDUCED BY ACUTE ORAL ...

    African Journals Online (AJOL)

    2018-02-28

    Feb 28, 2018 ... This study examines alcohol-induced cerebral cortex damage and the association with oxidative ... alcohol has profound effects on the function ... Chronic use of ..... Alcohol induced brain damage and liver damage in young.

  2. Effects of single-dose neuropeptide Y on levels of hippocampal BDNF, MDA, GSH, and NO in a rat model of pentylenetetrazole-induced epileptic seizure

    Directory of Open Access Journals (Sweden)

    Hale Maral Kir

    2013-11-01

    Full Text Available Epilepsy is one of the most common neurological disorders, characterized by recurrent seizures, which may increase the content of reactive oxygen and nitrogen species. Th e objective of this study was to investigate the eff ects of Neuropeptide Y on oxidative and nitrosative balance and brain-derived neurotrophic factor levels induced by pentylenetetrazole (a standard convulsant drug in the hippocampus of Wistar rats. Th ree groups of seven rats were treated intraperitoneally as follows: group  (saline + saline  ml saline, group  (salin + Pentylenetetrazole  ml saline  min before Pentylenetetrazole; and group  (Neuropeptide Y + Pentylenetetrazole  μg/kg Neuropeptide Y  min before  mg/kg Pentylenetetrazole. After  h, the animals were euthanized by decapitation. Hippocampus were isolated to evaluate the malondialdehyde, glutathione, nitric oxide, and brain-derived neurotrophic factor levels in three rat groups. Th e results of this study demonstrated that while intraperitoneally administered neuropeptide Y did not result in a statistically signifi cant diff erence in BDNF levels, its administration caused a statistically signifi cant decrease in malondialdehyde and nitric oxide levels and an increase in glutathione levels in rats with pentylenetetrazole-induced epileptic seizure. Neuropeptide Y were able to reduce nitroxidative damage induced by pentylenetetrazole in the hippocampus of Wistar rats.

  3. 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

    International Nuclear Information System (INIS)

    Hara, Yoshie; Nakamura, Mitsugu; Tamaki, Norihiko; Ehara, Kazumasa; Kitamura, Junji

    1998-01-01

    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.)

  4. 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.

  5. 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......, being involved in learning and memory processing. It has been demonstrated that METH induces significant alteration in mice striatal NPY, Y(1) and Y(2) receptor mRNA levels. However, the impact of this drug on the hippocampal NPY system and its consequences remain unknown. Thus, in this study, we...

  6. 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

  7. Region-specific aging of the human brain as evidenced by neurochemical profiles measured noninvasively in the posterior cingulate cortex and the occipital lobe using 1H magnetic resonance spectroscopy at 7 T.

    Science.gov (United States)

    Marjańska, Małgorzata; McCarten, J Riley; Hodges, James; Hemmy, Laura S; Grant, Andrea; Deelchand, Dinesh K; Terpstra, Melissa

    2017-06-23

    The concentrations of fourteen neurochemicals associated with metabolism, neurotransmission, antioxidant capacity, and cellular structure were measured noninvasively from two distinct brain regions using 1 H magnetic resonance spectroscopy. Seventeen young adults (age 19-22years) and sixteen cognitively normal older adults (age 70-88years) were scanned. To increase sensitivity and specificity, 1 H magnetic resonance spectra were obtained at the ultra-high field of 7T and at ultra-short echo time. The concentrations of neurochemicals were determined using water as an internal reference and accounting for gray matter, white matter, and cerebrospinal fluid content of the volume of interest. In the posterior cingulate cortex (PCC), the concentrations of neurochemicals associated with energy (i.e., creatine plus phosphocreatine), membrane turnover (i.e., choline containing compounds), and gliosis (i.e., myo-inositol) were higher in the older adults while the concentrations of N-acetylaspartylglutamate (NAAG) and phosphorylethanolamine (PE) were lower. In the occipital cortex (OCC), the concentration of N-acetylaspartate (NAA), a marker of neuronal viability, concentrations of the neurotransmitters Glu and NAAG, antioxidant ascorbate (Asc), and PE were lower in the older adults while the concentration of choline containing compounds was higher. Altogether, these findings shed light on how the human brain ages differently depending on region. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Classical neurotransmitters and neuropeptides involved in generalized epilepsy in a multi-neurotransmitter system: How to improve the antiepileptic effect?

    Science.gov (United States)

    Werner, Felix-Martin; Coveñas, Rafael

    2017-06-01

    Here, we describe in generalized epilepsies the alterations of classical neurotransmitters and neuropeptides acting at specific subreceptors. In order to consider a network context rather than one based on focal substrates and in order to make the interaction between neurotransmitters and neuropeptides and their specific subreceptors comprehensible, neural networks in the hippocampus, thalamus, and cerebral cortex are described. In this disease, a neurotransmitter imbalance between dopaminergic and serotonergic neurons and between presynaptic GABAergic neurons (hypoactivity) and glutaminergic neurons (hyperactivity) occurs. Consequently, combined GABA A agonists and NMDA antagonists could furthermore stabilize the neural networks in a multimodal pharmacotherapy. The antiepileptic effect and the mechanisms of action of conventional and recently developed antiepileptic drugs are reviewed. The GASH:Sal animal model can contribute to examine the efficacy of antiepileptic drugs. The issues of whether the interaction of classical neurotransmitters with other subreceptors (5-HT 7 , metabotropic 5 glutaminergic, A 2A adenosine, and alpha nicotinic 7 cholinergic receptors) or whether the administration of agonists/antagonists of neuropeptides might improve the therapeutic effect of antiepileptic drugs should be addressed. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Altered gene expression profiles in the hippocampus and prefrontal cortex of type 2 diabetic rats

    Directory of Open Access Journals (Sweden)

    Abdul-Rahman Omar

    2012-02-01

    Full Text Available Abstract Background There has been an increasing body of epidemiologic and biochemical evidence implying the role of cerebral insulin resistance in Alzheimer-type dementia. For a better understanding of the insulin effect on the central nervous system, we performed microarray-based global gene expression profiling in the hippocampus, striatum and prefrontal cortex of streptozotocin-induced and spontaneously diabetic Goto-Kakizaki rats as model animals for type 1 and type 2 diabetes, respectively. Results Following pathway analysis and validation of gene lists by real-time polymerase chain reaction, 30 genes from the hippocampus, such as the inhibitory neuropeptide galanin, synuclein gamma and uncoupling protein 2, and 22 genes from the prefrontal cortex, e.g. galanin receptor 2, protein kinase C gamma and epsilon, ABCA1 (ATP-Binding Cassette A1, CD47 (Cluster of Differentiation 47 and the RET (Rearranged During Transfection protooncogene, were found to exhibit altered expression levels in type 2 diabetic model animals in comparison to non-diabetic control animals. These gene lists proved to be partly overlapping and encompassed genes related to neurotransmission, lipid metabolism, neuronal development, insulin secretion, oxidative damage and DNA repair. On the other hand, no significant alterations were found in the transcriptomes of the corpus striatum in the same animals. Changes in the cerebral gene expression profiles seemed to be specific for the type 2 diabetic model, as no such alterations were found in streptozotocin-treated animals. Conclusions According to our knowledge this is the first characterization of the whole-genome expression changes of specific brain regions in a diabetic model. Our findings shed light on the complex role of insulin signaling in fine-tuning brain functions, and provide further experimental evidence in support of the recently elaborated theory of type 3 diabetes.

  10. 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.

  11. Genetic influences on thinning of the cerebral cortex during development

    NARCIS (Netherlands)

    van Soelen, I.L.C.; Brouwer, R.M.; van Baal, G.C.M.; Schnack, H.G.; Peper, J.S.; Collins, D.L.; Evans, A.C.; Kahn, R.S.; Boomsma, D.I.; Hulshoff Pol, H.E.

    2012-01-01

    During development from childhood to adulthood the human brain undergoes considerable thinning of the cerebral cortex. Whether developmental cortical thinning is influenced by genes and if independent genetic factors influence different parts of the cortex is not known. Magnetic resonance brain

  12. 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.

  13. The role for IGF-1-derived small neuropeptides as a therapeutic target for neurological disorders.

    Science.gov (United States)

    Guan, Jian; Harris, Paul; Brimble, Margaret; Lei, Yang; Lu, Jun; Yang, Yang; Gunn, Alistair J

    2015-06-01

    Exogenous IGF-1 protects the brain from ischemic injury and improves function. However, its clinical application to neurological disorders is limited by its large molecular size, poor central uptake and mitogenic potential. In this review, the authors have discussed the efficacy, pharmacokinetics and mechanisms of IGF-1 derivatives on protecting acute brain injury, preventing memory impairment and improving recovery from neurological degenerative conditions evaluated in various animal models. We have included natural metabolites of IGF-1, glycine-proline-glutamate (GPE), cleaved from N-terminal IGF-1 and cyclic glycine-proline (cGP) as well as the structural analogues of GPE and cGP, glycine-2-methyl-proline-glutamate and cyclo-l-glycyl-l-2-allylproline, respectively. In addition, the regulatory role for cGP in bioavailability of IGF-1 has also been discussed. These small neuropeptides provide effective neuroprotection by offering an improved pharmacokinetic profile and more practical route of administration compared with IGF-1 administration. Developing modified neuropeptides to overcome the limitations of their endogenous counterparts represents a novel strategy of pharmaceutical discovery for neurological disorders. The mechanism of action may involve a regulation of IGF-1 bioavailability.

  14. A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development.

    Science.gov (United States)

    Deng, Dazhi; Jian, Chongdong; Lei, Ling; Zhou, Yijing; McSweeney, Colleen; Dong, Fengping; Shen, Yilun; Zou, Donghua; Wang, Yonggang; Wu, Yuan; Zhang, Limin; Mao, Yingwei

    2017-10-17

    Mental illnesses like schizophrenia (SCZ) and major depression disorder (MDD) are devastating brain disorders. The SCZ risk gene, disrupted in schizophrenia 1 ( DISC1 ), has been associated with neuropsychiatric conditions. However, little is known regarding the long-lasting impacts on brain metabolism and behavioral outcomes from genetic insults on fetal NPCs during early life. We have established a new mouse model that specifically interrupts DISC1 functions in NPCs in vivo by a dominant-negative DISC1 (DN-DISC1) with a precise temporal and spatial regulation. Interestingly, prenatal interruption of mouse Disc1 function in NPCs leads to abnormal depression-like deficit in adult mice. Here we took a novel unbiased metabonomics approach to identify brain-specific metabolites that are significantly changed in DN-DISC1 mice. Surprisingly, the inhibitory neurotransmitter, GABA, is augmented. Consistently, parvalbumin (PV) interneurons are increased in the cingulate cortex, retrosplenial granular cortex, and motor cortex. Interestingly, somatostatin (SST) positive and neuropeptide Y (NPY) interneurons are decreased in some brain regions, suggesting that DN-DISC1 expression affects the localization of interneuron subtypes. To further explore the cellular mechanisms that cause this change, DN-DISC1 suppresses proliferation and promotes the cell cycle exit of progenitors in the medial ganglionic eminence (MGE), whereas it stimulates ectopic proliferation of neighboring cells through cell non-autonomous effect. Mechanistically, it modulates GSK3 activity and interrupts Dlx2 activity in the Wnt activation. In sum, our results provide evidence that specific genetic insults on NSCs at a short period of time could lead to prolonged changes of brain metabolism and development, eventually behavioral defects.

  15. 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...

  16. [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...

  17. Hyperphagia of hyperthyroidism: is neuropeptide Y involved?

    Science.gov (United States)

    Pétervári, Erika; Balaskó, Márta; Jech-Mihálffy, Andrea; Székely, Miklós

    2005-11-01

    The possible role of neuropeptide Y (NPY) was studied in rats with hypermetabolism and hyperphagia induced by thyroxine (50-100-200 microg/day s.c. for 3-4 weeks). Both metabolic rate and body temperature increased quickly with thyroxine treatment, while hyperphagia started to develop only after 2 weeks of treatment. The weight gain rate progressively decreased or stopped. The NPY-induced hyperphagia was not altered significantly during thyroxine treatment (in severe thyrotoxicosis it was rather suppressed); the fasting-induced hyperphagia was smaller than in controls following 1 week of treatment, and it became enhanced only after 3 weeks, when the deficit in body weight indicated a certain level of starvation already prior to the food deprivation. The NPY-antagonist D-Tyr27,36,D-Thr32-NPY27,36 suppressed this fasting-induced hyperphagia, suggesting that endogenous NPY is involved in this late phase. In conclusion, hyperthyroidism per se does not increase the NPY activity, instead the quickly developing hyperthermia may inhibit the NPY actions; NPY may, however, be activated by a concurrent hypermetabolism-induced starvation.

  18. Neuropeptide diversity and the regulation of social behavior in New World primates

    Science.gov (United States)

    French, Jeffrey A.; Taylor, Jack H.; Mustoe, Aaryn C.; Cavanaugh, Jon

    2016-01-01

    Oxytocin (OT) and vasopressin (AVP) are important hypothalamic neuropeptides that regulate peripheral physiology, and have emerged as important modulators of brain function, particularly in the social realm. OT structure and the genes that ultimately determine structure are highly conserved among diverse eutherian mammals, but recent discoveries have identified surprising variability in OT and peptide structure in New World monkeys (NWM), with five new OT variants identified to date. This review explores these new findings in light of comparative OT/AVP ligand evolution, documents coevolutionary changes in the oxytocin and vasopressin receptors (OTR and V1aR), and highlights the distribution of neuropeptidergic neurons and receptors in the primate brain. Finally, the behavioral consequences of OT and AVP in regulating NWM sociality are summarized, demonstrating important neuromodulatory effects of these compounds and OT ligand-specific influences in certain social domains. PMID:27020799

  19. MRI volumetry of prefrontal cortex

    Science.gov (United States)

    Sheline, Yvette I.; Black, Kevin J.; Lin, Daniel Y.; Pimmel, Joseph; Wang, Po; Haller, John W.; Csernansky, John G.; Gado, Mokhtar; Walkup, Ronald K.; Brunsden, Barry S.; Vannier, Michael W.

    1995-05-01

    Prefrontal cortex volumetry by brain magnetic resonance (MR) is required to estimate changes postulated to occur in certain psychiatric and neurologic disorders. A semiautomated method with quantitative characterization of its performance is sought to reliably distinguish small prefrontal cortex volume changes within individuals and between groups. Stereological methods were tested by a blinded comparison of measurements applied to 3D MR scans obtained using an MPRAGE protocol. Fixed grid stereologic methods were used to estimate prefrontal cortex volumes on a graphic workstation, after the images are scaled from 16 to 8 bits using a histogram method. In addition images were resliced into coronal sections perpendicular to the bicommissural plane. Prefrontal cortex volumes were defined as all sections of the frontal lobe anterior to the anterior commissure. Ventricular volumes were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was volumetry by stereology can yield accurate and repeatable measurements. Small frontal lobe volume reductions in patients with brain disorders such as depression and schizophrenia can be efficiently assessed using this method.

  20. Localization of insulin receptor mRNA in rat brain by in situ hybridization

    International Nuclear Information System (INIS)

    Marks, J.L.; Porte, D. Jr.; Stahl, W.L.; Baskin, D.G.

    1990-01-01

    Insulin receptor mRNA was demonstrated in rat brain slices by in situ hybridization with three 35 S-oligonucleotide probes and contact film autoradiography. Specificity was confirmed by showing that (a) excess unlabeled probe abolished the signal, (b) an oligonucleotide probe for rat neuropeptide Y mRNA showed a different distribution of hybridization signal, and (c) the distribution of insulin receptor binding was consistent with the distribution of insulin receptor mRNA. Insulin receptor mRNA was most abundant in the granule cell layers of the olfactory bulb, cerebellum and dentate gyrus, in the pyramidal cell body layers of the pyriform cortex and hippocampus, in the choroid plexus and in the arcuate nucleus of the hypothalamus

  1. 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.

  2. 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.

  3. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Visual Categorization and the Parietal Cortex

    Directory of Open Access Journals (Sweden)

    Jamie K Fitzgerald

    2012-05-01

    Full Text Available The primate brain is adept at rapidly grouping items and events into functional classes, or categories, in order to recognize the significance of stimuli and guide behavior. Higher cognitive functions have traditionally been considered the domain of frontal areas. However, increasing evidence suggests that parietal cortex is also involved in categorical and associative processes. Previous work showed that the parietal cortex is highly involved in spatial processing, attention and saccadic eye movement planning, and more recent studies have found decision-making signals in LIP. We recently found that a subdivision of parietal cortex, the lateral intraparietal area (LIP, reflects learned categories for multiple types of visual stimuli. Additionally, a comparison of categorization signals in parietal and frontal areas found stronger and earlier categorization signals in parietal cortex, arguing that parietal abstract association or category signals are unlikely to arise via feedback from prefrontal cortex (PFC.

  5. Genomics, transcriptomics, and peptidomics of Daphnia pulex neuropeptides and protein hormones

    DEFF Research Database (Denmark)

    Dircksen, Heinrich; Neupert, Susanne; Predel, Reinhard

    2011-01-01

    , neuroparsin, two neuropeptide-F splice forms, three periviscerokinins (but no pyrokinins), pigment dispersing hormone, proctolin, Met(4)-proctolin, short neuropeptide-F, three RYamides, SIFamide, two sulfakinins, and three tachykinins. There are two genes for a preprohormone containing orcomyotropin...

  6. Drosophila DH31 Neuropeptide and PDF Receptor Regulate Night-Onset Temperature Preference.

    Science.gov (United States)

    Goda, Tadahiro; Tang, Xin; Umezaki, Yujiro; Chu, Michelle L; Hamada, Fumika N

    2016-11-16

    Body temperature exhibits rhythmic fluctuations over a 24 h period (Refinetti and Menaker, 1992) and decreases during the night, which is associated with sleep initiation (Gilbert et al., 2004; Kräuchi, 2007a,b). However, the underlying mechanism of this temperature decrease is largely unknown. We have previously shown that Drosophila exhibit a daily temperature preference rhythm (TPR), in which their preferred temperatures increase during the daytime and then decrease at the transition from day to night (night-onset) (Kaneko et al., 2012). Because Drosophila are small ectotherms, their body temperature is very close to that of the ambient temperature (Stevenson, 1985), suggesting that their TPR generates their body temperature rhythm. Here, we demonstrate that the neuropeptide diuretic hormone 31 (DH31) and pigment-dispersing factor receptor (PDFR) contribute to regulate the preferred temperature decrease at night-onset. We show that PDFR and tethered-DH31 expression in dorsal neurons 2 (DN2s) restore the preferred temperature decrease at night-onset, suggesting that DH31 acts on PDFR in DN2s. Notably, we previously showed that the molecular clock in DN2s is important for TPR. Although PDF (another ligand of PDFR) is a critical factor for locomotor activity rhythms, Pdf mutants exhibit normal preferred temperature decreases at night-onset. This suggests that DH31-PDFR signaling specifically regulates a preferred temperature decrease at night-onset. Thus, we propose that night-onset TPR and locomotor activity rhythms are differentially controlled not only by clock neurons but also by neuropeptide signaling in the brain. Body temperature rhythm (BTR) is fundamental for the maintenance of functions essential for homeostasis, such as generating metabolic energy and sleep. One major unsolved question is how body temperature decreases dramatically during the night. Previously, we demonstrated that a BTR-like mechanism, referred to as temperature preference rhythm (TPR

  7. Beta-amyloid peptides undergo regulated co-secretion with neuropeptide and catecholamine neurotransmitters.

    Science.gov (United States)

    Toneff, Thomas; Funkelstein, Lydiane; Mosier, Charles; Abagyan, Armen; Ziegler, Michael; Hook, Vivian

    2013-08-01

    Beta-amyloid (Aβ) peptides are secreted from neurons, resulting in extracellular accumulation of Aβ and neurodegeneration of Alzheimer's disease. Because neuronal secretion is fundamental for the release of neurotransmitters, this study assessed the hypothesis that Aβ undergoes co-release with neurotransmitters. Model neuronal-like chromaffin cells were investigated, and results illustrate regulated, co-secretion of Aβ(1-40) and Aβ(1-42) with peptide neurotransmitters (galanin, enkephalin, and NPY) and catecholamine neurotransmitters (dopamine, norepinephrine, and epinephrine). Regulated secretion from chromaffin cells was stimulated by KCl depolarization and nicotine. Forskolin, stimulating cAMP, also induced co-secretion of Aβ peptides with peptide and catecholamine neurotransmitters. These data suggested the co-localization of Aβ with neurotransmitters in dense core secretory vesicles (DCSV) that store and secrete such chemical messengers. Indeed, Aβ was demonstrated to be present in DCSV with neuropeptide and catecholamine transmitters. Furthermore, the DCSV organelle contains APP and its processing proteases, β- and γ-secretases, that are necessary for production of Aβ. Thus, Aβ can be generated in neurotransmitter-containing DCSV. Human IMR32 neuroblastoma cells also displayed regulated secretion of Aβ(1-40) and Aβ(1-42) with the galanin neurotransmitter. These findings illustrate that Aβ peptides are present in neurotransmitter-containing DCSV, and undergo co-secretion with neuropeptide and catecholamine neurotransmitters that regulate brain functions. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Tailless and Atrophin control Drosophila aggression by regulating neuropeptide signalling in the pars intercerebralis

    Science.gov (United States)

    Davis, Shaun M.; Thomas, Amanda L.; Nomie, Krystle J.; Huang, Longwen; Dierick, Herman A.

    2014-02-01

    Aggressive behaviour is widespread throughout the animal kingdom. However, its mechanisms are poorly understood, and the degree of molecular conservation between distantly related species is unknown. Here we show that knockdown of tailless (tll) increases aggression in Drosophila, similar to the effect of its mouse orthologue Nr2e1. Tll localizes to the adult pars intercerebralis (PI), which shows similarity to the mammalian hypothalamus. Knockdown of tll in the PI is sufficient to increase aggression and is rescued by co-expressing human NR2E1. Knockdown of Atrophin, a Tll co-repressor, also increases aggression, and both proteins physically interact in the PI. tll knockdown-induced aggression is fully suppressed by blocking neuropeptide processing or release from the PI. In addition, genetically activating PI neurons increases aggression, mimicking the aggression-inducing effect of hypothalamic stimulation. Together, our results suggest that a transcriptional control module regulates neuropeptide signalling from the neurosecretory cells of the brain to control aggressive behaviour.

  9. Pharmacological or genetic orexin 1 receptor inhibition attenuates MK-801 induced glutamate release in mouse cortex

    Directory of Open Access Journals (Sweden)

    Leah eAluisio

    2014-05-01

    Full Text Available The orexin/hypocretin neuropeptides are produced by a cluster of neurons within the lateral posterior hypothalamus and participate in neuronal regulation by activating their receptors (OX1 and OX2 receptors. The orexin system projects widely through the brain and functions as an interface between multiple regulatory systems including wakefulness, energy balance, stress, reward and emotion. Recent studies have demonstrated that orexins and glutamate interact at the synaptic level and that orexins facilitate glutamate actions. We tested the hypothesis that orexins modulate glutamate signaling via OX1 receptors by monitoring levels of glutamate in frontal cortex of freely moving mice using enzyme coated biosensors under inhibited OX1 receptor conditions. MK-801, an NMDA receptor antagonist, was administered subcutaneously (0.178 mg/kg to indirectly disinhibit pyramidal neurons and therefore increase cortical glutamate release. In wild-type mice, pretreatment with the OX1 receptor antagonist GSK-1059865 (10 mg/kg S.C. which had no effect by itself, significantly attenuated the cortical glutamate release elicited by MK-801. OX1 receptor knockout mice had a blunted glutamate release response to MK-801 and exhibited about half of the glutamate release observed in wild-type mice in agreement with the data obtained with transient blockade of OX1 receptors. These results indicate that pharmacological (transient or genetic (permanent inhibition of the OX1 receptor similarly interfere with glutamatergic function in the cortex. Selectively targeting the OX1 receptor with an antagonist may normalize hyperglutamatergic states and thus may represent a novel therapeutic strategy for the treatment of various psychiatric disorders associated with hyperactive states.

  10. Tuning afferent synapses of hippocampal interneurons by neuropeptide Y

    DEFF Research Database (Denmark)

    Ledri, Marco; Sørensen, Andreas Toft; Erdelyi, Ferenc

    2011-01-01

    Cholecystokinin (CCK)-expressing basket cells encompass a subclass of inhibitory GABAergic interneurons that regulate memory-forming oscillatory network activity of the hippocampal formation in accordance to the emotional and motivational state of the animal, conveyed onto these cells by respective...... are modulated by neuropeptide Y (NPY), one of the major local neuropeptides that strongly inhibits hippocampal excitability and has significant effect on its memory function. Here, using GAD65-GFP transgenic mice for prospective identification of CCK basket cells and whole-cell patch-clamp recordings, we show...

  11. Developmental and sex-specific differences in expression of neuropeptides derived from allatotropin gene in the silkmoth Bombyx mori.

    Science.gov (United States)

    Bednár, Branislav; Roller, Ladislav; Čižmár, Daniel; Mitrová, Diana; Žitňan, Dušan

    2017-05-01

    Allatotropin (AT) and related neuropeptides are widespread bioactive molecules that regulate development, food intake and muscle contractions in insects and other invertebrates. In moths, alternative splicing of the at gene generates three mRNA precursors encoding AT with different combinations of three structurally similar AT-like peptides (ATLI-III). We used in situ hybridization and immunohistochemistry to map the differential expression of these transcripts during the postembryonic development of Bombyx mori. Transcript encoding AT alone was expressed in numerous neurons of the central nervous system and frontal ganglion, whereas transcripts encoding AT with ATLs were produced by smaller specific subgroups of neurons in larval stages. Metamorphosis was associated with considerable developmental changes and sex-specific differences in the expression of all transcripts. The most notable was the appearance of AT/ATL transcripts (1) in the brain lateral neurosecretory cells producing prothoracicotropic hormone; (2) in the male-specific cluster of about 20 neurons in the posterior region of the terminal abdominal ganglion; (3) in the female-specific medial neurons in the abdominal ganglia AG2-7. Immunohistochemical staining showed that these neurons produced a mixture of various neuropeptides and innervated diverse peripheral organs. Our data suggest that AT/ATL neuropeptides are involved in multiple stage- and sex-specific functions during the development of B. mori.

  12. Immunohistochemical localization of cardio-active neuropeptides in the heart of a living fossil, Nautilus pompilius L. (Cephalopoda, Tetrabranchiata).

    Science.gov (United States)

    Springer, J; Ruth, P; Beuerlein, K; Westermann, B; Schipp, R

    2004-01-01

    Neuropeptides play an important role in modulating the effects of neurotransmitters such as acetylcholine and noradrenaline in the heart and the vascular system of vertebrates and invertebrates. Various neuropeptides, including substance P (SP), vasoactive intestinal polypeptide (VIP) and FMRFamide, have been localized in the brain in cephalopods and the neurosecretory system of the vena cava. Previous studies involving cephalopods have mainly focussed on the modern, coleoid cephalopods, whereas little attention was paid to the living fossil Nautilus. In this study, the distributions of the peptides related to tachykinins (TKs) and the high affinity receptor for the best characterized TK substance P (tachykinin NK-1), VIP, as well as FMRFamide were investigated in the heart of Nautilus pompilius L. by immunohistochemistry. TK-like immunoreactivity (TK-LI) was seen associated to a sub-population of hemocytes, VIP-LI glial cells in larger nerves entering the heart, whereas FMRFamide immunoreactivity was distributed throughout the entire heart, including the semilunar atrioventricular valves. The pattern of FMRFamide immunoreactivity matched that of Bodian silver staining for nervous tissue. The NK-1-LI receptor was located on endothelial cells, which were also positive for endothelial nitric oxide synthase-LI (eNOS). The results indicate that neuropeptides may be involved in the regulation of the Nautilus heart via different mechanisms, (1) by direct interaction with myocardial receptors (FMRFamide), (2) by interacting with the nervus cardiacus (VIP-related peptides) and (3) indirectly by stimulating eNOS in the endothelium throughout the heart (TK-related peptides).

  13. Total numbers of neurons and glial cells in cortex and basal ganglia of aged brains with Down syndrome--a stereological study.

    Science.gov (United States)

    Karlsen, Anna Schou; Pakkenberg, Bente

    2011-11-01

    The total numbers of neurons and glial cells in the neocortex and basal ganglia in adults with Down syndrome (DS) were estimated with design-based stereological methods, providing quantitative data on brains affected by delayed development and accelerated aging. Cell numbers, volume of regions, and densities of neurons and glial cell subtypes were estimated in brains from 4 female DS subjects (mean age 66 years) and 6 female controls (mean age 70 years). The DS subjects were estimated to have about 40% fewer neocortical neurons in total (11.1 × 10(9) vs. 17.8 × 10(9), 2p ≤ 0.001) and almost 30% fewer neocortical glial cells with no overlap to controls (12.8 × 10(9) vs. 18.2 × 10(9), 2p = 0.004). In contrast, the total number of neurons in the basal ganglia was the same in the 2 groups, whereas the number of oligodendrocytes in the basal ganglia was reduced by almost 50% in DS (405 × 10(6) vs. 816 × 10(6), 2p = 0.01). We conclude that trisomy 21 affects cortical structures more than central gray matter emphasizing the differential impairment of brain development. Despite concomitant Alzheimer-like pathology, the neurodegenerative outcome in a DS brain deviates from common Alzheimer disease.

  14. 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.

  15. 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

  16. Insulin sensitivity : modulation by neuropeptides and hormones

    NARCIS (Netherlands)

    Hoek, Anita van den

    2006-01-01

    Nowadays, obesity has reached epidemic proportions globally. It can lead to several chronic diseases, including insulin resistance/type 2 diabetes mellitus. Feeding behaviour is regulated in the hypothalamus of the brain by two opposing pathways: NPY/AgRP neurons vs. POMC/CART neurons. In addition,

  17. 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.

    Science.gov (United States)

    Qiao, Jun; Jin, Guixing; Lei, Licun; Wang, Lan; Du, Yaqiang; Wang, Xueyi

    2016-01-01

    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 ( 1 H-MRS) in recently detoxified alcohol-dependent patients. 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. 1 H-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. 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. High-frequency right DLPFC rTMS was associated with improvement in memory dysfunction, which is correlated with levels of hippocampal brain metabolites detected by 1 H-MRS in recently detoxified alcohol-dependent patients.

  18. Expression of GFSKLYFamide-like neuropeptide in the digestive ...

    African Journals Online (AJOL)

    Neuropeptides are key mediators of physiological processes in animals and a considerable amount of information has been accumulated on their diversity and functions across phyla. However, progress in echinoderm neurobiology has been much slower than others. The sea cucumber Holothuria scabra is an ...

  19. Third ventricle neuropeptide-Y infusion effect on metabolic ...

    African Journals Online (AJOL)

    The goal of this study was to determine whether neuropeptide-Y affects the mean plasma concentrations of metabolic parameters such as thyroxine (T4), triiodothyronine (T3), growth hormone (GH), insulin, glucagon, glucose, fatty acid and urea in the goats fed different energy content in diets. 16 goats were randomly ...

  20. Neuropeptides and social behavior of rats tested in dyadic encounters

    NARCIS (Netherlands)

    Niesink, R.J.M.; Ree, J.M. van

    1984-01-01

    The effects of various neuropeptides on social behavior was studied in a test procedure in which 7-day isolated animals were tested together with non-isolated partners in dyadic encounters. The short-term isolation procedure increased the frequency and duration of social activities of the rats, but

  1. Mice lacking neuropeptide Y show increased sensitivity to cocaine

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Woldbye, David Paul Drucker

    2012-01-01

    There is increasing data implicating neuropeptide Y (NPY) in the neurobiology of addiction. This study explored the possible role of NPY in cocaine-induced behavior using NPY knockout mice. The transgenic mice showed a hypersensitive response to cocaine in three animal models of cocaine addiction...

  2. Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: Meta-analysis of controlled trials.

    Science.gov (United States)

    Aleman, André; Enriquez-Geppert, Stefanie; Knegtering, Henderikus; Dlabac-de Lange, Jozarni J

    2018-06-01

    Negative symptoms in schizophrenia concern a clinically relevant reduction of goal-directed behavior that strongly and negatively impacts daily functioning. Existing treatments are of marginal effect and novel approaches are needed. Noninvasive neurostimulation by means of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are novel approaches that may hold promise. To provide a quantitative integration of the published evidence regarding effects of rTMS and tDCS over the frontal cortex on negative symptoms, including an analysis of effects of sham stimulation. Meta-analysis was applied, using a random effects model, to calculate mean weighted effect sizes (Cohen's d). Heterogeneity was assessed by using Cochrans Q and I 2 tests. For rTMS treatment, the mean weighted effect size compared to sham stimulation was 0.64 (0.32-0.96; k = 22, total N = 827). Studies with younger participants showed stronger effects as compared to studies with older participants. For tDCS studies a mean weighted effect size of 0.50 (-0.07 to 1.07; k = 5, total N = 134) was found. For all frontal noninvasive neurostimulation studies together (i.e., TMS and tDCS studies combined) active stimulation was superior to sham, the mean weighted effect size was 0.61 (24 studies, 27 comparisons, 95% confidence interval 0.33-0.89; total N = 961). Sham rTMS (baseline - posttreatment comparison) showed a significant improvement of negative symptoms, d = 0.31 (0.09-0.52; k = 16, total N = 333). Whereas previous meta-analyses were underpowered, our meta-analysis had a power of 0.87 to detect a small effect. The available evidence indicates that noninvasive prefrontal neurostimulation can improve negative symptoms. This finding suggests a causal role for the lateral frontal cortex in self-initiated goal-directed behavior. The evidence is stronger for rTMS than for tDCS, although this may be due to the small number of

  3. Neurosteroid biosynthesis: enzymatic pathways and neuroendocrine regulation by neurotransmitters and neuropeptides.

    Science.gov (United States)

    Do Rego, Jean Luc; Seong, Jae Young; Burel, Delphine; Leprince, Jerôme; Luu-The, Van; Tsutsui, Kazuyoshi; Tonon, Marie-Christine; Pelletier, Georges; Vaudry, Hubert

    2009-08-01

    Neuroactive steroids synthesized in neuronal tissue, referred to as neurosteroids, are implicated in proliferation, differentiation, activity and survival of nerve cells. Neurosteroids are also involved in the control of a number of behavioral, neuroendocrine and metabolic processes such as regulation of food intake, locomotor activity, sexual activity, aggressiveness, anxiety, depression, body temperature and blood pressure. In this article, we summarize the current knowledge regarding the existence, neuroanatomical distribution and biological activity of the enzymes responsible for the biosynthesis of neurosteroids in the brain of vertebrates, and we review the neuronal mechanisms that control the activity of these enzymes. The observation that the activity of key steroidogenic enzymes is finely tuned by various neurotransmitters and neuropeptides strongly suggests that some of the central effects of these neuromodulators may be mediated via the regulation of neurosteroid production.

  4. Molecular cloning of a preprohormone from sea anemones containing numerous copies of a metamorphosis-inducing neuropeptide: a likely role for dipeptidyl aminopeptidase in neuropeptide precursor processing

    DEFF Research Database (Denmark)

    Leviev, I; Grimmelikhuijzen, C J

    1995-01-01

    a polyp, a medusa, and a planula larva stage. Recently, a neuropeptide, metamorphosis in a hydroid planula larva to become a hydropolyp [Leitz, T., Morand, K. & Mann, M. (1994) Dev. Biol. 163, 440-446]. Here, we have cloned...... the precursor protein for this metamorphosis-inducing neuropeptide from sea anemones. The precursor protein is 514-amino acid residues long and contains 10 copies of the immature, authentic neuropeptide (Gln-Gln-Pro-Gly-Leu-Trp-Gly). All neuropeptide copies are preceded by Xaa-Pro or Xaa-Ala sequences...

  5. Connectivity changes underlying neurofeedback training of visual cortex activity.

    Directory of Open Access Journals (Sweden)

    Frank Scharnowski

    Full Text Available Neurofeedback based on real-time functional magnetic resonance imaging (fMRI is a new approach that allows training of voluntary control over regionally specific brain activity. However, the neural basis of successful neurofeedback learning remains poorly understood. Here, we assessed changes in effective brain connectivity associated with neurofeedback training of visual cortex activity. Using dynamic causal modeling (DCM, we found that training participants to increase visual cortex activity was associated with increased effective connectivity between the visual cortex and the superior parietal lobe. Specifically, participants who learned to control activity in their visual cortex showed increased top-down control of the superior parietal lobe over the visual cortex, and at the same time reduced bottom-up processing. These results are consistent with efficient employment of top-down visual attention and imagery, which were the cognitive strategies used by participants to increase their visual cortex activity.

  6. Grit and the brain: spontaneous activity of the dorsomedial prefrontal cortex mediates the relationship between the trait grit and academic performance

    Science.gov (United States)

    Zhou, Ming; Chen, Taolin; Yang, Xun; Chen, Guangxiang; Wang, Meiyun; Gong, Qiyong

    2017-01-01

    Abstract As a personality trait, grit involves the tendency to strive to achieve long-term goals with continual passion and perseverance and plays an extremely crucial role in personal achievement. However, the neural mechanisms of grit remain largely unknown. In this study, we aimed to explore the association between grit and the fractional amplitude of low-frequency fluctuations (fALFF) in 217 healthy adolescent students using resting-state functional magnetic resonance imaging (RS-fMRI). We found that an individual’s grit was negatively related to the regional fALFF in the right dorsomedial prefrontal cortex (DMPFC), which is involved in self-regulation, planning, goal setting and maintenance, and counterfactual thinking for reflecting on past failures. The results persisted even after the effects of general intelligence and the ‘big five’ personality traits were adjusted for. More importantly, the fALFF of the right DMPFC played a mediating role in the association between grit and academic performance. Overall, these findings reveal regional fALFF as a neural basis of grit and highlight the right DMPFC as a neural link between grit and academic performance. PMID:27672175

  7. Correlation between the Appearance of Neuropeptides in the Rat Trigeminal Ganglion and Reinnervation of the Healing Root Socket after Tooth Extraction

    International Nuclear Information System (INIS)

    Gunjigake, Kaori K.; Goto, Tetsuya; Nakao, Kayoko; Konoo, Tetsuro; Kobayashi, Shigeru; Yamaguchi, Kazunori

    2006-01-01

    The neuropeptide substance P (SP) modulates bone metabolism. This study examined the temporal appearance of the neuropeptides SP and brain-derived nerve growth factor (BDNF) and their receptors (neurokinin-1 receptor (NK 1 -R) and Trk B, respectively) in the rat trigeminal ganglion to investigate the role of neuropeptides in healing after tooth extraction. Rats were anesthetized and their upper right first molars were extracted; the rats were sacrificed 3 hours and 1–21 days after extraction. Their trigeminal ganglion and maxilla were removed, and cryosections were prepared and immunostained using specific antibodies against SP, BDNF, NK 1 -R, and Trk B. In the tooth sockets after extraction, new bone and a few SP-immunoreactive nerve fibers were first seen at day 7, and bone completely filled the sockets at day 21. In the trigeminal ganglion, the proportions of NK 1 -R-, BDNF-, and Trk B-immunoreactive neurons changed similarly, i.e., they initially decreased, increased rapidly to maximum levels by day 3, and then decreased gradually to control levels until 21 days. These findings suggest that the appearance of neuropeptides in the trigeminal ganglion, the reinnervation of SP-immunoreactive nerve fibers, and bone repair in the tooth socket during healing after extraction were correlated

  8. Tobacco dependence, the insular cortex and the hypocretin connection

    Science.gov (United States)

    Kenny, Paul J.

    2010-01-01

    Tobacco use is a major cause of disease and premature death in the United States. Nicotine is considered the key component of tobacco responsible for addiction in human smokers. Accumulating evidence supports an important role for the hypocretin (orexin) neuropeptide system in regulating the reinforcing properties of most major drugs of abuse, including nicotine. Here, data showing that nicotine activates hypocretin-producing neurons in the lateral hypothalamus, and that disruption of hypocretin transmission decreases nicotine self-administration behavior in rats will be reviewed. Recent findings suggesting that plasma hypocretin levels may be related to the magnitude of cigarette craving in abstinent smokers will be discussed. Finally, data suggesting that hypocretin transmission in the insular cortex may play an important role in regulating nicotine self-administration behavior in rats will be reviewed. This latter finding may provide mechanistic insight into the apparent disruption of tobacco addiction reported in human smokers with stroke-associated damage to the insular cortex. PMID:20816891

  9. Khat distorts the prefrontal cortex histology and function of adult ...

    African Journals Online (AJOL)

    Khat is a psychoactive herbal drug of pronounced ethno-pharmacological significance often abused due to its unregulated use. It affects many brain centers including the prefrontal cortex which is the anterior most part of the frontal lobe. The prefrontal cortex modulates working memory, planning complex cognitive ...

  10. Modality-specific involvement of occipital cortex in Early Blind?

    NARCIS (Netherlands)

    van der Lubbe, Robert Henricus Johannes; van Mierlo, C.M.; Postma, A.

    2008-01-01

    What happens in occipital cortex when neuronal activity is no longer evoked by regular visual stimulation? Studying brain activity induced by tactile and auditory stimuli in the blind may provide an answer. Several studies indicate that occipital cortex in the blind is recruited in simple tasks,

  11. Role of Nitric Oxide in Radioinduced Effects in Developing Brain Cortex; Rol del Oxido Nitrico en los Efectos Radioinducidos en Corteza Cerebral en Desarrollo

    Energy Technology Data Exchange (ETDEWEB)

    Robello, E [Instituto Balseiro, Universidad Nacional de Cuyo, Centro Atomico Bariloche, Universidad de Buenos Aires (Argentina)

    2001-07-01

    Nowadays, prenatal exposure is a very important topic in radiopathology.Unfortunately, pregnant women have been sometimes exposed or have to expose to ionising radiation, for example, during a medical treatment.There are lots of studies made by the International Commission of Radiation Protection (ICRP) about the effects of ionising radiation and the consequences that are suffered by the exposed foetus.Hence, it has been argued that developing mammalian brain is substantially more susceptible to teratogenic insult than most other embryonic and foetal structures.Presumably, this reflects its architectural complexity, its long developmental period, the vulnerability of the undifferentiated neural cell and the inability of the brain to replace lost neurones.Furthermore, there is abundant information on the biological effects caused by prenatal exposure of mammals to ionising radiation.Only two conspicuous effects on brain growth and development have emerged thus far in the study of atomic bomb survivors exposed prenatally in Hiroshima and Nagasaki.These are some cases of severe mental retardation and some of small head size without apparent metal retardation. Additionally, groups within the survivors have shown significantly reduced IQ scores.This increase would be dose-related and, if the shift of IQ had no clear dose threshold, might, in turn, show no threshold.Besides, it has been studied that ionising radiation implies molecular ionisation and excitation in the biological systems.When radiation has a high linear transfer energy (LET) damage may be produce trough energy absorbed directly by the target molecule (direct mechanism).However, when radiation has a low LET (like {gamma} and X radiation), and without forgetting that biological systems are basically aqueous, damage may be produce trough generation of species highly reactive (like free radicals and reactive oxygen species - ROS) by molecules of water which has adsorbed energy radiation (indirect mechanism

  12. 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

  13. Functional magnetic resonance imaging of the primary motor cortex ...

    Indian Academy of Sciences (India)

    Unknown

    brain is able to control the muscles in the body in a pre- cise and efficient ... which receives inputs from the prefrontal cortex and the ... This is based on the fact that oxygenated blood ... compared with deoxygenated blood (paramagnetic) and.

  14. 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.

  15. Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging.

    Science.gov (United States)

    Tarantini, Stefano; Tucsek, Zsuzsanna; Valcarcel-Ares, M Noa; Toth, Peter; Gautam, Tripti; Giles, Cory B; Ballabh, Praveen; Wei, Jeanne Y; Wren, Jonathan D; Ashpole, Nicole M; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2016-08-01

    Strong epidemiological and experimental evidence indicate that both age and hypertension lead to significant functional and structural impairment of the cerebral microcirculation, predisposing to the development of vascular cognitive impairment (VCI) and Alzheimer's disease. Preclinical studies establish a causal link between cognitive decline and microvascular rarefaction in the hippocampus, an area of brain important for learning and memory. Age-related decline in circulating IGF-1 levels results in functional impairment of the cerebral microvessels; however, the mechanistic role of IGF-1 deficiency in impaired hippocampal microvascularization remains elusive. The present study was designed to characterize the additive/synergistic effects of IGF-1 deficiency and hypertension on microvascular density and expression of genes involved in angiogenesis and microvascular regression in the hippocampus. To achieve that goal, we induced hypertension in control and IGF-1 deficient mice (Igf1 f/f  + TBG-Cre-AAV8) by chronic infusion of angiotensin II. We found that circulating IGF-1 deficiency is associated with decreased microvascular density and exacerbates hypertension-induced microvascular rarefaction both in the hippocampus and the neocortex. The anti-angiogenic hippocampal gene expression signature observed in hypertensive IGF-1 deficient mice in the present study provides important clues for subsequent studies to elucidate mechanisms by which hypertension may contribute to the pathogenesis and clinical manifestation of VCI. In conclusion, adult-onset, isolated endocrine IGF-1 deficiency exerts deleterious effects on the cerebral microcirculation, leading to a significant decline in cortical and hippocampal capillarity and exacerbating hypertension-induced cerebromicrovascular rarefaction. The morphological impairment of the cerebral microvasculature induced by IGF-1 deficiency and hypertension reported here, in combination with neurovascular uncoupling, increased

  16. Excessive oral intake caffeine altered cerebral cortex ...

    African Journals Online (AJOL)

    Caffeine is commonly consumed in an effort to enhance speed in performance and wakefulness. However, little is known about the deleterious effects it can produce on the brain, this study aimed at determining the extents of effects and damage that can be caused by excessive consumption of caffeine on the cerebral cortex ...

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

    Science.gov (United States)

    Sabihi, Sara; Dong, Shirley M.; Durosko, Nicole E.; Leuner, Benedetta

    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, but not virgin, females. In addition, OTR blockade in the postpartum mPFC impaired maternal care behaviors and enhanced maternal aggression. Overall, these results suggest that OT in the mPFC modulates maternal care and aggression, as well as anxiety-like behavior, during the postpartum period. Although the relationship among these behaviors is complicated and further investigation is required to refine our understanding of OT actions in the maternal mPFC, these data nonetheless provide new insights into neural circuitry of OT-mediated postpartum behaviors. PMID:25147513

  18. Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex.

    Science.gov (United States)

    Chiba, Shuichi; Numakawa, Tadahiro; Ninomiya, Midori; Richards, Misty C; Wakabayashi, Chisato; Kunugi, Hiroshi

    2012-10-01

    Stress and the resulting increase in glucocorticoid levels have been implicated in the pathophysiology of depressive disorders. We investigated the effects of chronic restraint stress (CRS: 6 hours × 28 days) on anxiety- and depression-like behaviors in rats and on the possible changes in glucocorticoid receptor (GR) expression as well as brain-derived neurotrophic factor (BDNF)-dependent neural function in the prefrontal cortex (PFC). We observed significant reductions in body weight gain, food intake and sucrose preference from 1 week after the onset of CRS. In the 5th week of CRS, we conducted open-field (OFT), elevated plus-maze (EPM) and forced swim tests (FST). We observed a decrease in the number of entries into open arms during the EPM (anxiety-like behavior) and increased immobility during the FST (depression-like behavior). When the PFC was removed after CRS and subject to western blot analysis, the GR expression reduced compared with control, while the levels of BDNF and its receptors remained unchanged. Basal glutamate concentrations in PFC acute slice which were measured by high performance liquid chromatography were not influenced by CRS. However, BDNF-induced glutamate release was attenuated after CRS. These results suggest that reduced GR expression and altered BDNF function may be involved in chronic stress-induced anxiety--and depression-like behaviors. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Mas-allatotropin in the developing antennal lobe of the sphinx moth Manduca sexta: distribution, time course, developmental regulation, and colocalization with other neuropeptides.

    Science.gov (United States)

    Utz, Sandra; Huetteroth, Wolf; Vömel, Matthias; Schachtner, Joachim

    2008-01-01

    The paired antennal lobes (ALs) of the sphinx moth Manduca sexta serve as a well-established model for studying development of the primary integration centers for odor information in the brain. To further reveal the role of neuropeptides during AL development, we have analyzed cellular distribution, developmental time course, and regulation of the neuropeptide M. sexta allatotropin (Mas-AT). On the basis of morphology and appearance during AL formation, seven major types of Mas-AT-immunoreactive (ir) cells could be distinguished. Mas-AT-ir cells are identified as local, projection, and centrifugal neurons, which are either persisting larval or newly added adult-specific neurons. Complementary immunostaining with antisera against two other neuropeptide families (A-type allatostatins, RFamides) revealed colocalization within three of the Mas-AT-ir cell types. On the basis of this neurochemistry, the most prominent type of Mas-AT-ir neurons, the local AT neurons (LATn), could be divided in three subpopulations. The appearance of the Mas-AT-ir cell types occurring during metamorphosis parallels the rising titer of the developmental hormone 20-hydroxyecdysone (20E). Artificially shifting the 20E titer to an earlier developmental time point resulted in the precocious occurrence of Mas-AT immunostaining. This result supports the hypothesis that the pupal rise of 20E is causative for Mas-AT expression during AL development. Comparing localization and developmental time course of Mas-AT and other neuropeptides with the time course of AL formation suggests various functions for these neuropeptides during development, including an involvement in the formation of the olfactory glomeruli.

  20. Prefrontal Cortex Dysfunction in Fragile X Mice Depends on the Continued Absence of Fragile X Mental Retardation Protein in the Adult Brain.

    Science.gov (United States)

    Siegel, Jennifer J; Chitwood, Raymond A; Ding, James M; Payne, Clayton; Taylor, William; Gray, Richard; Zemelman, Boris V; Johnston, Daniel

    2017-08-02

    Fragile X Syndrome (FX) is generally considered a developmental disorder, arising from a mutation that disrupts the transcription of Fragile X Mental Retardation Protein (FMRP). However, FMRP regulates the transcription of other proteins and participates in an unknown number of protein-protein interactions throughout life. In addition to known developmental issues, it is thus likely that some dysfunction is also due to the ongoing absence of FMRP. Dissociating dysfunction due to developmental dysregulation from dysfunction due to the continued absence of FMRP is necessary to understand the different roles of FMRP and to treat patients effectively throughout life. We show here that FX model mice display substantial deficits in a PFC-dependent task. We then use conditional knock-out mice to eliminate FMRP only in the PFC alone of adult mice. We observe an increase in the proportion of nonlearners and a delay in the onset of learning in both FX and conditional knock-out mice. The results suggest that these deficits (1) are due to the absence of FMRP in the PFC alone and (2) are not the result of developmental dysregulation. Furthermore, PFC-associated deficits are rescued by initiating production of FMRP in adult conditional restoration mice, suggesting that PFC dysfunction may persist as long as FMRP is absent and therefore can be rescued after development. The data suggest that it is possible to dissociate the roles of FMRP in neural function from developmental dysregulation, and that PFC function can be restored in the adult FX brain. SIGNIFICANCE STATEMENT The absence of Fragile X Mental Retardation Protein (FMRP) from birth results in developmental disabilities and lifelong impairments. We show here that in mouse models PFC dysfunction in Fragile X Syndrome (FX) can be attributed to the continued absence of FMRP from the PFC, independent of FMRP status during development. Furthermore, initiation of FMRP production in the PFC of adult FX animals rescues PFC

  1. Neuropeptide Y - an early biomarker for cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

    Schebesch, Karl-Michael; Brawanski, Alexander; Bele, Sylvia; Schödel, Petra; Herbst, Andreas; Bründl, Elisabeth; Kagerbauer, Simone Maria; Martin, Jan; Lohmeier, Anette; Stoerr, Eva-Maria; Proescholdt, Martin

    2013-12-01

    In the human brain, the potent vasoconstrictive neuropeptide Y (NPY) is abundantly expressed. Neuropeptide Y, which is stored in perivascular nerve fibers of the cerebral arteries, regulates the cerebral vascular diameter as well as cerebral blood flow. However, the role of NPY in the pathogenesis of cerebral vasospasm (CV) related to subarachnoid hemorrhage (SAH) is unclear. We prospectively analyzed and compared the release of endogenous NPY in the cerebrospinal fluid (CSF) of 66 patients with SAH to NPY release in a control group. Additionally, we correlated the levels of NPY with CV and consecutive ischemic stroke. Sixty-six consecutive patients (40 women, 26 men; mean age 53·1 years) with aneurysmal SAH were included. In the SAH group, CSF was drawn daily from day 1 to day 10 after the onset of SAH. The CSF of 29 patients undergoing spinal anesthesia for orthopedic surgery served as control samples. The NPY levels were determined in duplicate CSF samples by means of a competitive enzyme immunoassay (EIA). The levels of NPY in CSF were correlated with the development of CV over the 10-day period after the onset of SAH and to the occurrence of consecutive ischemic stroke. To evaluate CSF NPY levels as a predictive biomarker for vasospasm, we calculated the sensitivity and specificity as well as the positive and negative predictive values. The NPY levels were significantly higher in the SAH group than in the control group (p 0·05). Patients with CV showed significantly higher NPY levels than patients without CV during the entire observation period. The NPY levels of the non-CV group dissipated over time, whereas the CV group showed continuously increasing values. The NPY levels from day 4 to 10 were significantly higher in patients with CV-related stroke than in non-stroke patients. Using 0·3 ng/ml as a cut-off value, NPY levels on day 3 predicted the occurrence of CV with a sensitivity and specificity of 82% and 72%, respectively. High NPY levels, starting on

  2. Exploring the Sea Urchin Neuropeptide Landscape by Mass Spectrometry.

    Science.gov (United States)

    Monroe, Eric B; Annangudi, Suresh P; Wadhams, Andinet A; Richmond, Timothy A; Yang, Ning; Southey, Bruce R; Romanova, Elena V; Schoofs, Liliane; Baggerman, Geert; Sweedler, Jonathan V

    2018-05-01

    Neuropeptides are essential cell-to-cell signaling messengers and serve important regulatory roles in animals. Although remarkable progress has been made in peptide identification across the Metazoa, for some phyla such as Echinodermata, limited neuropeptides are known and even fewer have been verified on the protein level. We employed peptidomic approaches using bioinformatics and mass spectrometry (MS) to experimentally confirm 23 prohormones and to characterize a new prohormone in nervous system tissue from Strongylocentrotus purpuratus, the purple sea urchin. Ninety-three distinct peptides from known and novel prohormones were detected with MS from extracts of the radial nerves, many of which are reported or experimentally confirmed here for the first time, representing a large-scale study of neuropeptides from the phylum Echinodermata. Many of the identified peptides and their precursor proteins have low homology to known prohormones from other species/phyla and are unique to the sea urchin. By pairing bioinformatics with MS, the capacity to characterize novel peptides and annotate prohormone genes is enhanced. Graphical Abstract.

  3. Exploring the Sea Urchin Neuropeptide Landscape by Mass Spectrometry

    Science.gov (United States)

    Monroe, Eric B.; Annangudi, Suresh P.; Wadhams, Andinet A.; Richmond, Timothy A.; Yang, Ning; Southey, Bruce R.; Romanova, Elena V.; Schoofs, Liliane; Baggerman, Geert; Sweedler, Jonathan V.

    2018-04-01

    Neuropeptides are essential cell-to-cell signaling messengers and serve important regulatory roles in animals. Although remarkable progress has been made in peptide identification across the Metazoa, for some phyla such as Echinodermata, limited neuropeptides are known and even fewer have been verified on the protein level. We employed peptidomic approaches using bioinformatics and mass spectrometry (MS) to experimentally confirm 23 prohormones and to characterize a new prohormone in nervous system tissue from Strongylocentrotus purpuratus, the purple sea urchin. Ninety-three distinct peptides from known and novel prohormones were detected with MS from extracts of the radial nerves, many of which are reported or experimentally confirmed here for the first time, representing a large-scale study of neuropeptides from the phylum Echinodermata. Many of the identified peptides and their precursor proteins have low homology to known prohormones from other species/phyla and are unique to the sea urchin. By pairing bioinformatics with MS, the capacity to characterize novel peptides and annotate prohormone genes is enhanced. [Figure not available: see fulltext.

  4. Neuropeptides, neurogenic inflammation and complex regional pain syndrome (CRPS).

    Science.gov (United States)

    Birklein, Frank; Schmelz, Martin

    2008-06-06

    This review explains symptoms and nature of neuropeptide signaling and its importance for clinical symptoms of CRPS. Neurogenic inflammation regularly accompanies excitation of primary afferent nociceptors. It has two major components-plasma extravasation and vasodilatation. The most important mediators are the calcitonin gene-related peptide (CGRP) and substance P (SP). After peripheral trauma immune reaction (e.g. cytokines) and the attempts of the tissue to regenerate (e.g. growth factors) sensitize nociceptors and amplify neurogenic inflammation. This cascade of events has been demonstrated in rat models of CRPS. Clinical findings in these animals strongly resemble clinical findings in CRPS, and can be prevented by anti-cytokine and anti-neuropeptide treatment. In CRPS patients, there is meanwhile also plenty of evidence that neurogenic inflammation contributes to clinical presentation. Increased cytokine production was demonstrated, as well as facilitated neurogenic inflammation. Very recently even "non-inflammatory" signs of CRPS (hyperhidrosis, cold skin) have been linked to neuropeptide signaling. Surprisingly, there was even moderately increased neurogenic inflammation in unaffected body regions. This favors the possibility that CRPS patients share genetic similarities. The future search for genetic commonalities will help us to further unravel the "mystery" CRPS.

  5. Exploring the Sea Urchin Neuropeptide Landscape by Mass Spectrometry

    Science.gov (United States)

    Monroe, Eric B.; Annangudi, Suresh P.; Wadhams, Andinet A.; Richmond, Timothy A.; Yang, Ning; Southey, Bruce R.; Romanova, Elena V.; Schoofs, Liliane; Baggerman, Geert; Sweedler, Jonathan V.

    2018-05-01

    Neuropeptides are essential cell-to-cell signaling messengers and serve important regulatory roles in animals. Although remarkable progress has been made in peptide identification across the Metazoa, for some phyla such as Echinodermata, limited neuropeptides are known and even fewer have been verified on the protein level. We employed peptidomic approaches using bioinformatics and mass spectrometry (MS) to experimentally confirm 23 prohormones and to characterize a new prohormone in nervous system tissue from Strongylocentrotus purpuratus, the purple sea urchin. Ninety-three distinct peptides from known and novel prohormones were detected with MS from extracts of the radial nerves, many of which are reported or experimentally confirmed here for the first time, representing a large-scale study of neuropeptides from the phylum Echinodermata. Many of the identified peptides and their precursor proteins have low homology to known prohormones from other species/phyla and are unique to the sea urchin. By pairing bioinformatics with MS, the capacity to characterize novel peptides and annotate prohormone genes is enhanced. [Figure not available: see fulltext.

  6. Characterization of normal and supersensitive dopamine receptors: Effects of ergot drugs and neuropeptides

    International Nuclear Information System (INIS)

    Fuxe, K.; Agnati, L.F.; Koehler, C.; Kuonen, D.; Oegren, S.-O.; Andersson, K.; Hoekfelt, T.; Astra Pharmaceuticals AB, Soedertaelje; Modena Univ.

    1981-01-01

    Dopamine receptors have been characterized by use of radiolabelled dopamine agonists and antagonists. Using ibotenic acid induced lesions of the striatum, evidence was obtained that 3 H-N-propylnorapomorphine ( 3 H-NPA) binding sites and 3H-bromocriptine binding sites are located both on intrastriatal nerve cells and on extrinsic nerve terminals probably mainly originating in the cerebral cortex. Following a 6-hydroxydopamine induced lesion supersensitive dopamine receptors, an increase of binding sites for 3 H-NPA and after one year two different binding sites and behavioural supersensitivity have been observed. The dopamine receptor agonists and especially the dopaminergic ergot derivates have been characterized by studying their affinities for 3 H-bromocriptine, 3 H-spiperone 3 H-ADTN and 3 H-NPA binding sites in vitro and their effects on the specific in vivo binding of 3 H-spiperone and 3 H-NPA has been studied. There might exist 3 types of dopamine-receptors. Actions of dopaminergic ergot drugs have been evaluated at supersensitive dopamine receptors. There is a highly preferential action of CF25-397 at these receptors. Prolonged treatment with pergolide can produce a down regulation of normal dopamine receptors by reducing the density of such receptors. Colecystokinin peptides can in vitro reduce the number of 3 H-NPA binding sites in the striatum. Thus neuropeptides may represent neuromodulators in the dopamine synapses. (M.J.)

  7. A radial glia-specific role of RhoA in double cortex formation

    DEFF Research Database (Denmark)

    Cappello, Silvia; Böhringer, Christian R J; Bergami, Matteo

    2012-01-01

    disorders: subcortical band heterotopia (SBH), a heterotopic cortex underlying the normotopic cortex, and cobblestone lissencephaly, in which neurons protrude beyond layer I at the pial surface of the brain. Surprisingly, RhoA(-/-) neurons migrated normally when transplanted into wild-type cerebral cortex...

  8. Atypical brain lateralisation in the auditory cortex and language performance in 3- to 7-year-old children with high-functioning autism spectrum disorder: a child-customised magnetoencephalography (MEG) study.

    Science.gov (United States)

    Yoshimura, Yuko; Kikuchi, Mitsuru; Shitamichi, Kiyomi; Ueno, Sanae; Munesue, Toshio; Ono, Yasuki; Tsubokawa, Tsunehisa; Haruta, Yasuhiro; Oi, Manabu; Niida, Yo; Remijn, Gerard B; Takahashi, Tsutomu; Suzuki, Michio; Higashida, Haruhiro; Minabe, Yoshio

    2013-10-08

    significant predictor of shorter P50m latency in the right hemisphere. Using a child-customised MEG device, we studied the P50m component that was evoked through binaural human voice stimuli in young ASD and TD children to examine differences in auditory cortex function that are associated with language development. Our results suggest that there is atypical brain function in the auditory cortex in young children with ASD, regardless of language development.

  9. Peptide YY receptors in the brain

    International Nuclear Information System (INIS)

    Inui, A.; Oya, M.; Okita, M.

    1988-01-01

    Radiolabelled ligand binding studies demonstrated that specific receptors for peptide YY are present in the porcine as well as the canine brains. Peptide YY was bound to brain tissue membranes via high-affinity (dissociation constant, 1.39 X 10(-10)M) and low-affinity (dissociation constant, 3.72 X 10(-8)M) components. The binding sites showed a high specificity for peptide YY and neuropeptide Y, but not for pancreatic polypeptide or structurally unrelated peptides. The specific activity of peptide YY binding was highest in the hippocampus, followed by the pituitary gland, the hypothalamus, and the amygdala of the porcine brain, this pattern being similarly observed in the canine brain. The results suggest that peptide YY and neuropeptide Y may regulate the function of these regions of the brain through interaction with a common receptor site

  10. IGF-1 derived small neuropeptides and analogues: a novel strategy for the development of pharmaceuticals for neurological conditions.

    Science.gov (United States)

    Guan, Jian; Gluckman, Peter D

    2009-07-01

    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 it is also neuroprotective after ischemic injury, which provided a novel strategy of drug discovery for 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. G-2meth-PE, a GPE analogue designed to be more enzymatic resistant, has a prolonged plasma half-life and is more potent in neuroprotection. Neuroprotection by GPE and its analogue may involve modulation of inflammation, promotion of astrocytosis, inhibition of apoptosis and vascular remodelling. Acute administration of GPE also prevents 6-OHDA-induced nigrostrial dopamine depletion. Delayed treatment with GPE does not prevent dopamine loss, but improves long-term function. Cyclo-glycyl-proline (cyclic Gly-Pro) is an endogenous DKP that may be derived from GPE. Cyclic Gly-Pro and its analogue cyclo-L-glycyl-L-2-allylproline (NNZ 2591) are both neuroprotective after ischaemic injury. NNZ2591 is highly enzymatic resistant and centrally accessible. Its peripheral administration improves somatosensory-motor function and long-term histological outcome after brain injury. Our research suggests that small neuropeptides have advantages over growth factors in the treatment of brain injury, and that modified neuropeptides designed to overcome the limitations of their endogenous counterparts represent a novel strategy of pharmaceutical discovery for neurological disorders.

  11. A single-nucleotide polymorphism of human neuropeptide s gene originated from Europe shows decreased bioactivity.

    Directory of Open Access Journals (Sweden)

    Cheng Deng

    Full Text Available Using accumulating SNP (Single-Nucleotide Polymorphism data, we performed a genome-wide search for polypeptide hormone ligands showing changes in the mature regions to elucidate genotype/phenotype diversity among various human populations. Neuropeptide S (NPS, a brain peptide hormone highly conserved in vertebrates, has diverse physiological effects on anxiety, fear, hyperactivity, food intake, and sleeping time through its cognate receptor-NPSR. Here, we report a SNP rs4751440 (L(6-NPS causing non-synonymous substitution on the 6(th position (V to L of the NPS mature peptide region. L(6-NPS has a higher allele frequency in Europeans than other populations and probably originated from European ancestors ~25,000 yrs ago based on haplotype analysis and Approximate Bayesian Computation. Functional analyses indicate that L(6-NPS exhibits a significant lower bioactivity than the wild type NPS, with ~20-fold higher EC50 values in the stimulation of NPSR. Additional evolutionary and mutagenesis studies further demonstrate the importance of the valine residue in the 6(th position for NPS functions. Given the known physiological roles of NPS receptor in inflammatory bowel diseases, asthma pathogenesis, macrophage immune responses, and brain functions, our study provides the basis to elucidate NPS evolution and signaling diversity among human populations.

  12. Developmental Ethanol Exposure Causes Reduced Feeding and Reveals a Critical Role for Neuropeptide F in Survival

    Science.gov (United States)

    Guevara, Amanda; Gates, Hillary; Urbina, Brianna; French, Rachael

    2018-01-01

    Food intake is necessary for survival, and natural reward circuitry has evolved to help ensure that animals ingest sufficient food to maintain development, growth, and survival. Drugs of abuse, including alcohol, co-opt the natural reward circuitry in the brain, and this is a major factor in the reinforcement of drug behaviors leading to addiction. At the junction of these two aspects of reward are alterations in feeding behavior due to alcohol consumption. In particular, developmental alcohol exposure (DAE) results in a collection of physical and neurobehavioral disorders collectively referred to as Fetal Alcohol Spectrum Disorder (FASD). The deleterious effects of DAE include intellectual disabilities and other neurobehavioral changes, including altered feeding behaviors. Here we use Drosophila melanogaster as a genetic model organism to study the effects of DAE on feeding behavior and the expression and function of Neuropeptide F. We show that addition of a defined concentration of ethanol to food leads to reduced feeding at all stages of development. Further, genetic conditions that reduce or eliminate NPF signaling combine with ethanol exposure to further reduce feeding, and the distribution of NPF is altered in the brains of ethanol-supplemented larvae. Most strikingly, we find that the vast majority of flies with a null mutation in the NPF receptor die early in larval development when reared in ethanol, and provide evidence that this lethality is due to voluntary starvation. Collectively, we find a critical role for NPF signaling in protecting against altered feeding behavior induced by developmental ethanol exposure. PMID:29623043

  13. Agmatine attenuates nicotine induced conditioned place preference in mice through modulation of neuropeptide Y system.

    Science.gov (United States)

    Kotagale, Nandkishor R; Walke, Sonali; Shelkar, Gajanan P; Kokare, Dadasaheb M; Umekar, Milind J; Taksande, Brijesh G

    2014-04-01

    The purpose of the present study was to examine the effect of agmatine on nicotine induced conditioned place preference (CPP) in male albino mice. Intra-peritoneal (ip) administration of nicotine (1mg/kg) significantly increased time spent in drug-paired compartment. Agmatine (20 and 40 mg/kg, ip) co-administered with nicotine during the 6 days conditioning sessions completely abolished the acquisition of nicotine-induced CPP in mice. Concomitant administration of neuropeptide Y (NPY) (1 pg/mouse, icv) or [Leu(31), Pro(34)]-NPY (0.1 pg/mouse, icv), selective NPY Y1 receptor agonist potentiated the inhibitory effect of agmatine (10 mg/kg, ip) on nicotine CPP. Conversely, pretreatment with NPY Y1 receptor antagonist, BIBP3226 (0.01 ng/mouse, icv) blocked the effect of agmatine (20 mg/kg, ip) on nicotine induced CPP. In immunohistochemical study, nicotine decreased NPY-immunoreactivity in nucleus accumbens shell (AcbSh), bed nucleus of stria terminalis, lateral part (BNSTl), arcuate nucleus (ARC) and paraventricular nucleus (PVN). Conversely, administration of agmatine prior to the nicotine significantly reversed the effect of nicotine on NPY-immunoreactivity in the above brain nuclei. This data indicate that agmatine attenuate nicotine induced CPP via modulation of NPYergic neurotransmission in brain. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Oxytocin in the amygdala and not the prefrontal cortex enhances fear and impairs extinction in the juvenile rat.

    Science.gov (United States)

    Kritman, Milly; Lahoud, Nisrine; Maroun, Mouna

    2017-05-01

    A growing body of evidence suggests that the hypothalamic neuropeptide oxytocin (OT), aside from its central role in the regulation of social behavior, reduces fear and anxiety. The functional and opposing interactions of the medial prefrontal cortex (mPFC) and the amygdala in regulation of fear provide a unique experimental setting to examine the effects of OT on fear and extinction. Recent evidence suggests that in the adult animal OT can play a dual role in the regulation of fear leading to contrasting effects on fear depending on the manipulated brain region and the time of manipulations. The OT system is one of the systems that undergoes major changes throughout development, however, its role in regulating fear in young animals has not been widely explored. We recently showed that the mechanisms of extinction, and specifically engagement of the mPFC in extinction, are not identical in adult and juvenile animals. Thus, the purpose of this study was to elucidate the effects of OT on fear and extinction in juvenile animals. To that end, we determine extinction, by measuring freezing at different time points, following microinjection of the OT agonist, TGOT, into the mPFC, the basolateral and the central nuclei of the amygdala (BLA and CeA, respectively). The results show that whereas TGOT microinjections into the IL-mPFC did not affect extinction, microinjections into the amygdala were mainly associated with enhanced fear and impaired extinction. These results further emphasize the differences between adult and juvenile brains. Copyright © 2017. Published by Elsevier Inc.

  15. Reproductive neuropeptides that stimulate spawning in the Sydney Rock Oyster (Saccostrea glomerata).

    Science.gov (United States)

    In, Vu Van; Ntalamagka, Nikoleta; O'Connor, Wayne; Wang, Tianfang; Powell, Daniel; Cummins, Scott F; Elizur, Abigail

    2016-08-01

    The Sydney Rock Oyster, Saccostrea glomerata, is a socioeconomically important species in Australia, yet little is known about the molecular mechanism that regulates its reproduction. To address this gap, we have performed a combination of high throughput transcriptomic and peptidomic analysis, to identify genes and neuropeptides that are expressed in the key regulatory tissues of S. glomerata; the visceral ganglia and gonads. Neuropeptides are known to encompass a diverse class of peptide messengers that play functional roles in many aspects of an animal's life, including reproduction. Approximately 28 neuropeptide genes were identified, primarily within the visceral ganglia transcriptome, that encode precursor proteins containing numerous neuropeptides; some were confirmed through mass spectral peptidomics analysis of the visceral ganglia. Of those, 28 bioactive neuropeptides were synthesized, and then tested for their capacity to induce gonad development and spawning in S. glomerata. Egg laying hormone, gonadotropin-releasing hormone, APGWamide, buccalin, CCAP and LFRFamide were neuropeptides found to trigger spawning in ripe animals. Additional testing of APGWa and buccalin demonstrated their capacity to advance conditioning and gonadal maturation. In summary, our analysis of S. glomerata has identified neuropeptides that can influence the reproductive cycle of this species, specifically by accelerating gonadal maturation and triggering spawning. Other molluscan neuropeptides identified in this study will enable further research into understanding the neuroendocrinology of oysters, which may benefit their cultivation. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  16. Vesicle capture, not delivery, scales up neuropeptide storage in neuroendocrine terminals.

    Science.gov (United States)

    Bulgari, Dinara; Zhou, Chaoming; Hewes, Randall S; Deitcher, David L; Levitan, Edwin S

    2014-03-04

    Neurons vary in their capacity to produce, store, and release neuropeptides packaged in dense-core vesicles (DCVs). Specifically, neurons used for cotransmission have terminals that contain few DCVs and many small synaptic vesicles, whereas neuroendocrine neuron terminals contain many DCVs. Although the mechanistic basis for presynaptic variation is unknown, past research demonstrated transcriptional control of neuropeptide synthesis suggesting that supply from the soma limits presynaptic neuropeptide accumulation. Here neuropeptide release is shown to scale with presynaptic neuropeptide stores in identified Drosophila cotransmitting and neuroendocrine terminals. However, the dramatic difference in DCV number in these terminals occurs with similar anterograde axonal transport and DCV half-lives. Thus, differences in presynaptic neuropeptide stores are not explained by DCV delivery from the soma or turnover. Instead, greater neuropeptide accumulation in neuroendocrine terminals is promoted by dramatically more efficient presynaptic DCV capture. Greater capture comes with tradeoffs, however, as fewer uncaptured DCVs are available to populate distal boutons and replenish neuropeptide stores following release. Finally, expression of the Dimmed transcription factor in cotransmitting neurons increases presynaptic DCV capture. Therefore, DCV capture in the terminal is genetically controlled and determines neuron-specific variation in peptidergic function.

  17. Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures

    DEFF Research Database (Denmark)

    Gøtzsche, Casper René; Nikitidou, Litsa; Sørensen, Andreas Toft

    2012-01-01

    We recently demonstrated that recombinant adeno-associated viral vector-induced hippocampal overexpression of neuropeptide Y receptor, Y2, exerts a seizure-suppressant effect in kindling and kainate-induced models of epilepsy in rats. Interestingly, additional overexpression of neuropeptide Y...

  18. Short neuropeptide F acts as a functional neuromodulator for olfactory memory in Kenyon cells of Drosophila mushroom bodies.

    Science.gov (United States)

    Knapek, Stephan; Kahsai, Lily; Winther, Asa M E; Tanimoto, Hiromu; Nässel, Dick R

    2013-03-20

    In insects, many complex behaviors, including olfactory memory, are controlled by a paired brain structure, the so-called mushroom bodies (MB). In Drosophila, the development, neuroanatomy, and function of intrinsic neurons of the MB, the Kenyon cells, have been well characterized. Until now, several potential neurotransmitters or neuromodulators of Kenyon cells have been anatomically identified. However, whether these neuroactive substances of the Kenyon cells are functional has not been clarified yet. Here we show that a neuropeptide precursor gene encoding four types of short neuropeptide F (sNPF) is required in the Kenyon cells for appetitive olfactory memory. We found that activation of Kenyon cells by expressing a thermosensitive cation channel (dTrpA1) leads to a decrease in sNPF immunoreactivity in the MB lobes. Targeted expression of RNA interference against the sNPF precursor in Kenyon cells results in a highly significant knockdown of sNPF levels. This knockdown of sNPF in the Kenyon cells impairs sugar-rewarded olfactory memory. This impairment is not due to a defect in the reflexive sugar preference or odor response. Consistently, knockdown of sNPF receptors outside the MB causes deficits in appetitive memory. Altogether, these results suggest that sNPF is a functional neuromodulator released by Kenyon cells.

  19. Seasonal Variation in Group Size Is Related to Seasonal Variation in Neuropeptide Receptor Density.

    Science.gov (United States)

    Wilson, Leah C; Goodson, James L; Kingsbury, Marcy A

    2016-01-01

    In many species, seasonal variation in grouping behavior is widespread, with shifts towards territoriality in the breeding season and grouping in the winter. Compared to the hormonal and neural mechanisms of seasonal territorial aggression, the mechanisms that promote seasonal grouping have received little attention. We collected brains in spring and winter from wild-caught males of two species of emberizid sparrows that seasonally flock (the field sparrow, Spizella pusilla, and the dark-eyed junco, Junco hyemalis) and two species that do not seasonally flock (the song sparrow, Melospiza melodia, and the eastern towhee, Pipilo erythrophthalmus). We used receptor autoradiography to quantify seasonal plasticity in available binding sites for three neuropeptides known to influence social behavior. We examined binding sites for 125I-vasoactive intestinal polypeptide (VIP), 125I-sauvagine (SG, a ligand for corticotropin-releasing hormone receptors) and 125I-ornithine vasotocin analog (OVTA, a ligand for the VT3 nonapeptide). For all species and ligands, brain areas that exhibited a seasonal pattern in binding density were characterized by a winter increase. Compared to nonflocking species, seasonally flocking species showed different binding patterns in multiple brain areas. Furthermore, we found that winter flocking was associated with elevated winter 125I-VIP binding density in the medial amygdala, as well as 125I-VIP and 125I-OVTA binding density in the rostral arcopallium. While the functional significance of the avian rostral arcopallium is unclear, it may incorporate parts of the pallial amygdala. Our results point to this previously undescribed area as a likely hot spot of social modulation. © 2016 S. Karger AG, Basel.

  20. Bioacoustic Signal Classification in Cat Auditory Cortex

    Science.gov (United States)

    1994-01-01

    of the cat’s WINER. 1. A. Anatomy of layer IV in cat primary auditory cortex t4,1). J miedial geniculate body Ideintified by projections to binaural...34language" (see for example Tartter, 1986, chapter 8; and Lieberman, 1984). Attempts have been made to train animals (mainly apes, gorillas , _ _ ___I 3...gestures of a gorilla : Language acquisition in another Pongid. Brain and Language, 1978a, 5, 72-97. Patterson, F. Conversations with a gorilla

  1. Diversity of Neuropeptide Cell-Cell Signaling Molecules Generated by Proteolytic Processing Revealed by Neuropeptidomics Mass Spectrometry

    Science.gov (United States)

    Hook, Vivian; Lietz, Christopher B.; Podvin, Sonia; Cajka, Tomas; Fiehn, Oliver

    2018-04-01

    Neuropeptides are short peptides in the range of 3-40 residues that are secreted for cell-cell communication in neuroendocrine systems. In the nervous system, neuropeptides comprise the largest group of neurotransmitters. In the endocrine system, neuropeptides function as peptide hormones to coordinate intercellular signaling among target physiological systems. The diversity of neuropeptide functions is defined by their distinct primary sequences, peptide lengths, proteolytic processing of pro-neuropeptide precursors, and covalent modifications. Global, untargeted neuropeptidomics mass spectrometry is advantageous for defining the structural features of the thousands to tens of thousands of neuropeptides present in biological systems. Defining neuropeptide structures is the basis for defining the proteolytic processing pathways that convert pro-neuropeptides into active peptides. Neuropeptidomics has revealed that processing of pro-neuropeptides occurs at paired basic residues sites, and at non-basic residue sites. Processing results in neuropeptides with known functions and generates novel peptides representing intervening peptide domains flanked by dibasic residue processing sites, identified by neuropeptidomics. While very short peptide products of 2-4 residues are predicted from pro-neuropeptide dibasic processing sites, such peptides have not been readily identified; therefore, it will be logical to utilize metabolomics to identify very short peptides with neuropeptidomics in future studies. Proteolytic processing is accompanied by covalent post-translational modifications (PTMs) of neuropeptides comprising C-terminal amidation, N-terminal pyroglutamate, disulfide bonds, phosphorylation, sulfation, acetylation, glycosylation, and others. Neuropeptidomics can define PTM features of neuropeptides. In summary, neuropeptidomics for untargeted, global analyses of neuropeptides is essential for elucidation of proteases that generate diverse neuropeptides for cell

  2. Diversity of Neuropeptide Cell-Cell Signaling Molecules Generated by Proteolytic Processing Revealed by Neuropeptidomics Mass Spectrometry

    Science.gov (United States)

    Hook, Vivian; Lietz, Christopher B.; Podvin, Sonia; Cajka, Tomas; Fiehn, Oliver

    2018-05-01

    Neuropeptides are short peptides in the range of 3-40 residues that are secreted for cell-cell communication in neuroendocrine systems. In the nervous system, neuropeptides comprise the largest group of neurotransmitters. In the endocrine system, neuropeptides function as peptide hormones to coordinate intercellular signaling among target physiological systems. The diversity of neuropeptide functions is defined by their distinct primary sequences, peptide lengths, proteolytic processing of pro-neuropeptide precursors, and covalent modifications. Global, untargeted neuropeptidomics mass spectrometry is advantageous for defining the structural features of the thousands to tens of thousands of neuropeptides present in biological systems. Defining neuropeptide structures is the basis for defining the proteolytic processing pathways that convert pro-neuropeptides into active peptides. Neuropeptidomics has revealed that processing of pro-neuropeptides occurs at paired basic residues sites, and at non-basic residue sites. Processing results in neuropeptides with known functions and generates novel peptides representing intervening peptide domains flanked by dibasic residue processing sites, identified by neuropeptidomics. While very short peptide products of 2-4 residues are predicted from pro-neuropeptide dibasic processing sites, such peptides have not been readily identified; therefore, it will be logical to utilize metabolomics to identify very short peptides with neuropeptidomics in future studies. Proteolytic processing is accompanied by covalent post-translational modifications (PTMs) of neuropeptides comprising C-terminal amidation, N-terminal pyroglutamate, disulfide bonds, phosphorylation, sulfation, acetylation, glycosylation, and others. Neuropeptidomics can define PTM features of neuropeptides. In summary, neuropeptidomics for untargeted, global analyses of neuropeptides is essential for elucidation of proteases that generate diverse neuropeptides for cell

  3. Inhibition of systemic inflammation by central action of the neuropeptide alpha-melanocyte- stimulating hormone.

    Science.gov (United States)

    Delgado Hernàndez, R; Demitri, M T; Carlin, A; Meazza, C; Villa, P; Ghezzi, P; Lipton, J M; Catania, A

    1999-01-01

    The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) reduces fever and acute inflammation in the skin when administered centrally. The aim of the present research was to determine whether central alpha-MSH can also reduce signs of systemic inflammation in mice with endotoxemia. Increases in serum tumor necrosis factor-alpha and nitric oxide, induced by intraperitoneal administration of endotoxin, were modulated by central injection of a small concentration of alpha-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central alpha-MSH. Lung myeloperoxidase activity, a marker of neutrophil infiltration, was increased in endotoxemic mice; the increase was significantly less in lungs of mice treated with central alpha-MSH. Intraperitoneal administration of the small dose of alpha-MSH that was effective centrally did not alter any of the markers of inflammation. In experiments using immunoneutralization of central alpha-MSH, we tested the idea that endogenous peptide induced within the brain during systemic inflammation modulates host responses to endotoxic challenge in peripheral tissues. The data showed that proinflammatory agents induced by endotoxin in the circulation, lungs, and liver were significantly greater after blockade of central alpha-MSH. The results suggest that anti-inflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation.

  4. The orexin neuropeptide system: Physical activity and hypothalamic function throughout the aging process.

    Directory of Open Access Journals (Sweden)

    Anastasia N Zink

    2014-11-01

    Full Text Available There is a rising medical need for novel therapeutic targets of physical activity. Physical activity spans from spontaneous, low intensity movements to voluntary, high-intensity exercise. Regulation of spontaneous and voluntary movement is distributed over many brain areas and neural substrates, but the specific cellular and molecular mechanisms responsible for mediating overall activity levels are not well understood. The hypothalamus plays a central role in the control of physical activity, which is executed through coordination of multiple signaling systems, including the orexin neuropeptides. Orexin producing neurons integrate physiological and metabolic information to coordinate multiple behavioral states and modulate physical activity in response to the environment. This review is organized around three questions: (1 How do orexin peptides modulate physical activity? (2 What are the effects of aging and lifestyle choices on physical activity? (3 What are the effects of aging on hypothalamic function and the orexin peptides? Discussion of these questions will provide a summary of the current state of knowledge regarding hypothalamic orexin regulation of physical activity during aging and provide a platform on which to develop improved clinical outcomes in age-associated obesity and metabolic syndromes.

  5. Neuropeptide s alters anxiety but not depression-like behaviors in the flinders sensitive line rats, a genetic animal model

    DEFF Research Database (Denmark)

    Mathe, A.; Wegener, Gregers; Finger, B.

    2010-01-01

    Background: Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behavior in rodents. However, little knowledge is available to what extent the NPS system is involved in depression-related behaviors. The aim of the present work was to characterize...... the effects of centrally administered NPS on depression- and anxiety-related behaviors, using a well validated animal model of depression, the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL). Methods: Male and female were tested. Seven days following insertion....... In selected animals effect of NPS on home cage activity was explored. Finally, brains from separate groups of naive animals were harvested; hippocampi, amygdalae and PVN punched out, and mRNA transcripts measured with the real-time quantitative polymerase chain reaction (rt-qPCR). Results: The most salient...

  6. Myopic (HD-PTP, PTPN23) selectively regulates synaptic neuropeptide release.

    Science.gov (United States)

    Bulgari, Dinara; Jha, Anupma; Deitcher, David L; Levitan, Edwin S

    2018-02-13

    Neurotransmission is mediated by synaptic exocytosis of neuropeptide-containing dense-core vesicles (DCVs) and small-molecule transmitter-containing small synaptic vesicles (SSVs). Exocytosis of both vesicle types depends on Ca 2+ and shared secretory proteins. Here, we show that increasing or decreasing expression of Myopic (mop, HD-PTP, PTPN23), a Bro1 domain-containing pseudophosphatase implicated in neuronal development and neuropeptide gene expression, increases synaptic neuropeptide stores at the Drosophila neuromuscular junction (NMJ). This occurs without altering DCV content or transport, but synaptic DCV number and age are increased. The effect on synaptic neuropeptide stores is accounted for by inhibition of activity-induced Ca 2+ -dependent neuropeptide release. cAMP-evoked Ca 2+ -independent synaptic neuropeptide release also requires optimal Myopic expression, showing that Myopic affects the DCV secretory machinery shared by cAMP and Ca 2+ pathways. Presynaptic Myopic is abundant at early endosomes, but interaction with the endosomal sorting complex required for transport III (ESCRT III) protein (CHMP4/Shrub) that mediates Myopic's effect on neuron pruning is not required for control of neuropeptide release. Remarkably, in contrast to the effect on DCVs, Myopic does not affect release from SSVs. Therefore, Myopic selectively regulates synaptic DCV exocytosis that mediates peptidergic transmission at the NMJ.

  7. Effects of Neuropeptides and Mechanical Loading on Bone Cell Resorption in Vitro

    Directory of Open Access Journals (Sweden)

    Yeong-Min Yoo

    2014-04-01

    Full Text Available Neuropeptides such as vasoactive intestinal peptide (VIP and calcitonin gene-related peptide (CGRP are present in nerve fibers of bone tissues and have been suggested to potentially regulate bone remodeling. Oscillatory fluid flow (OFF-induced shear stress is a potent signal in mechanotransduction that is capable of regulating both anabolic and catabolic bone remodeling. However, the interaction between neuropeptides and mechanical induction in bone remodeling is poorly understood. In this study, we attempted to quantify the effects of combined neuropeptides and mechanical stimuli on mRNA and protein expression related to bone resorption. Neuropeptides (VIP or CGRP and/or OFF-induced shear stress were applied to MC3T3-E1 pre-osteoblastic cells and changes in receptor activator of nuclear factor kappa B (NF-κB ligand (RANKL and osteoprotegerin (OPG mRNA and protein levels were quantified. Neuropeptides and OFF-induced shear stress similarly decreased RANKL and increased OPG levels compared to control. Changes were not further enhanced with combined neuropeptides and OFF-induced shear stress. These results suggest that neuropeptides CGRP and VIP have an important role in suppressing bone resorptive activities through RANKL/OPG pathway, similar to mechanical loading.

  8. C. elegans Stress-Induced Sleep Emerges from the Collective Action of Multiple Neuropeptides.

    Science.gov (United States)

    Nath, Ravi D; Chow, Elly S; Wang, Han; Schwarz, Erich M; Sternberg, Paul W

    2016-09-26

    The genetic basis of sleep regulation remains poorly understood. In C. elegans, cellular stress induces sleep through epidermal growth factor (EGF)-dependent activation of the EGF receptor in the ALA neuron. The downstream mechanism by which this neuron promotes sleep is unknown. Single-cell RNA sequencing of ALA reveals that the most highly expressed, ALA-enriched genes encode neuropeptides. Here we have systematically investigated the four most highly enriched neuropeptides: flp-7, nlp-8, flp-24, and flp-13. When individually removed by null mutation, these peptides had little or no effect on stress-induced sleep. However, stress-induced sleep was abolished in nlp-8; flp-24; flp-13 triple-mutant animals, indicating that these neuropeptides work collectively in controlling stress-induced sleep. We tested the effect of overexpression of these neuropeptide genes on five behaviors modulated during sleep-pharyngeal pumping, defecation, locomotion, head movement, and avoidance response to an aversive stimulus-and we found that, if individually overexpressed, each of three neuropeptides (nlp-8, flp-24, or flp-13) induced a different suite of sleep-associated behaviors. These overexpression results raise the possibility that individual components of sleep might be specified by individual neuropeptides or combinations of neuropeptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal.

    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

    2013-10-01

    The neuropeptide oxytocin has been implicated in a variety of social processes. However, recent studies indicate that oxytocin does not enhance prosocial behavior in all people in all circumstances. Here, we investigate effects of intranasal oxytocin administration on intrinsic functional brain connectivity with resting state functional magnetic resonance imaging. Participants were 42 women who received a nasal spray containing either 16 IU of oxytocin or a placebo and reported how often their mother used love withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior. We found that oxytocin changes functional connectivity between the posterior cingulate cortex (PCC) and the brainstem. In the oxytocin group there was a positive connectivity between these regions, whereas the placebo group showed negative connectivity. In addition, oxytocin induced functional connectivity changes between the PCC, the cerebellum and the postcentral gyrus, but only for those participants who experienced low levels of maternal love withdrawal. We speculate that oxytocin enhances prosocial behavior by influencing complex brain networks involved in self-referential processing and affectionate touch, most prominently in individuals with supportive family backgrounds. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  10. Dorsomedial prefontal cortex supports spontaneous thinking per se.

    Science.gov (United States)

    Raij, T T; Riekki, T J J

    2017-06-01

    Spontaneous thinking, an action to produce, consider, integrate, and reason through mental representations, is central to our daily experience and has been suggested to serve crucial adaptive purposes. Such thinking occurs among other experiences during mind wandering that is associated with activation of the default mode network among other brain circuitries. Whether and how such brain activation is linked to the experience of spontaneous thinking per se remains poorly known. We studied 51 healthy subjects using a comprehensive experience-sampling paradigm during 3T functional magnetic resonance imaging. In comparison with fixation, the experiences of spontaneous thinking and spontaneous perception were related to activation of wide-spread brain circuitries, including the cortical midline structures, the anterior cingulate cortex and the visual cortex. In direct comparison of the spontaneous thinking versus spontaneous perception, activation was observed in the anterior dorsomedial prefrontal cortex. Modality congruence of spontaneous-experience-related brain activation was suggested by several findings, including association of the lingual gyrus with visual in comparison with non-verbal-non-visual thinking. In the context of current literature, these findings suggest that the cortical midline structures are involved in the integrative core substrate of spontaneous thinking that is coupled with other brain systems depending on the characteristics of thinking. Furthermore, involvement of the anterior dorsomedial prefrontal cortex suggests the control of high-order abstract functions to characterize spontaneous thinking per se. Hum Brain Mapp 38:3277-3288, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. A neuroprotective brain-penetrating endopeptidase fusion protein ameliorates Alzheimer disease pathology and restores neurogenesis.

    Science.gov (United States)

    Spencer, Brian; Verma, Inder; Desplats, Paula; Morvinski, Dinorah; Rockenstein, Ed; Adame, Anthony; Masliah, Eliezer

    2014-06-20

    Alzheimer disease (AD) is characterized by widespread neurodegeneration throughout the association cortex and limbic system, deposition of amyloid-β peptide (Aβ) in the neuropil and around the blood vessels, and formation of neurofibrillary tangles. The endopeptidase neprilysin has been successfully used to reduce the accumulation of Aβ following intracranial viral vector delivery or ex vivo manipulated intracranial delivery. These therapies have relied on direct injections into the brain, whereas a clinically desirable therapy would involve i.v. infusion of a recombinant enzyme. We previously characterized a recombinant neprilysin that contained a 38-amino acid brain-targeting domain. Recombinant cell lines have been generated expressing this brain-targeted enzyme (ASN12). In this report, we characterize the ASN12 recombinant protein for pharmacology in a mouse as well as efficacy in two APPtg mouse models of AD. The recombinant ASN12 transited to the brain with a t½ of 24 h and accumulated to 1.7% of injected dose at 24 h following i.v. delivery. We examined pharmacodynamics in the tg2576 APPtg mouse with the prion promoter APP695 SWE mutation and in the Line41 mThy1 APP751 mutation mouse. Treatment of either APPtg mouse resulted in reduced Aβ, increased neuronal synapses, and improved learning and memory. In addition, the Line41 APPtg mice showed increased levels of C-terminal neuropeptide Y fragments and increased neurogenesis. These results suggest that the recombinant brain-targeted neprilysin, ASN12, may be an effective treatment for AD and warrant further investigation in clinical trials. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Neuropeptide K is present in human cerebrospinal fluid

    International Nuclear Information System (INIS)

    Toresson, G.; de las Carreras, C.; Brodin, E.; Bertilsson, L.

    1990-01-01

    Neurokinin A-like immunoreactivity (NKA-LI) in human cerebrospinal fluid (CSF) was determined by radioimmuno assay (RIA) combined with high performance liquid chromatography (HPLC). The major immunoreactive component did not coelute with NKA, but coeluted with neuropeptide K (NPK), which contains the NKA sequence in its C-terminus. Trypsin treatment of this component from human CSF and of synthetic NPK, produced a substance which coeluted with NKA in the HPLC system. When the NKA-LI was oxidized with hydrogen peroxide and rechromatographed, the immunoreactivity coeluted with NPK sulfoxide. The results indicate that the main part of the NKA-LI in CSF is identical with NPK. The mean concentration of NPK measured in CSF from 6 healthy subjects by HPLC-RIA was 23 + 11 (SD) pmol/L

  13. The prefrontal cortex shows context-specific changes in effective connectivity to motor or visual cortex during the selection of action or colour

    DEFF Research Database (Denmark)

    Rowe, James B.; Stephan, Klaas E.; Friston, Karl

    2005-01-01

    The role of the prefrontal cortex remains controversial. Neuroimaging studies support modality-specific and process-specific functions related to working memory and attention. Its role may also be defined by changes in its influence over other brain regions including sensory and motor cortex. We...... used functional magnetic imaging (fMRI) to study the free selection of actions and colours. Control conditions used externally specified actions and colours. The prefrontal cortex was activated during free selection, regardless of modality, in contrast to modality-specific activations outside...... included high-order interactions between modality, selection and regional activity. There was greater coupling between prefrontal cortex and motor cortex during free selection and action tasks, and between prefrontal cortex and visual cortex during free selection of colours. The results suggest...

  14. Laparoscopic adrenal cortex

    International Nuclear Information System (INIS)

    Peyrolou, A.; Salom, A.; Harguindeguy; Taroco, L.; Ardao, G.; Broli, F. . E mail: andresssss@adinet.com.uy

    2005-01-01

    The paper presents the case of a female patient who carried an aldosterone-secreting tumor of adrenal cortex.In the analysis of diagnosis and para clinical examinations there is particular reference to the laparoscopic surgery mode of treatment.Diagnosis should be established on the basis of clinical and laboratory tests (hypopotassemia and hyperaldosteronism).Tumor topography was confirmed through CT scan, MRI and Scintiscan in left adrenal cortex.Resection was consequently made through laparoscopic surgery.The patients evolution was excellent from the surgical viewpoint,with I levels of blood pressure, potassium and aldosterone returned to normal

  15. Plasticity in the Prefrontal Cortex of Adult Rats

    Directory of Open Access Journals (Sweden)

    Bryan eKolb

    2015-02-01

    Full Text Available We review the plastic changes of the prefrontal cortex of the rat in response to a wide range of experiences including sensory and motor experience, gonadal hormones, psychoactive drugs, learning tasks, stress, social experience, metaplastic experiences, and brain injury. Our focus is on synaptic changes (dendritic morphology and spine density in pyramidal neurons and the relationship to behavioral changes. The most general conclusion we can reach is that the prefrontal cortex is extremely plastic and that the medial and orbital prefrontal regions frequently respond very differently to the same experience in the same brain and the rules that govern prefrontal plasticity appear to differ for those of other cortical regions.

  16. Analytic framework for peptidomics applied to large-scale neuropeptide identification

    DEFF Research Database (Denmark)

    Secher, Anna; Kelstrup, Christian D; Conde-Frieboes, Kilian W

    2016-01-01

    was integrated with publically available databases. We developed and applied an algorithm that reduces the peptide complexity for identification of biologically relevant peptides. The developed pipeline was applied to rat hypothalamus and identifies thousands of neuropeptides and their post...

  17. Clinical significance of serum neuropeptide Y levels changes in chronic obstructive pulmonary diseases

    International Nuclear Information System (INIS)

    Jin Yuanhong; Pan Jiongwei; Cao Zhuo; Ji Naijun

    2004-01-01

    Objective: To study the clinical significance of serum neuropeptide Y level changes in patients with chronic obstructive pulmonary diseases (COPD). Methods: The serum neuropeptide Y levels were determined by radioimmunoassay in 40 patients with chronic obstructive pulmonary diseases (COPD) and 30 patients without COPD. Results: Mean serum neuropeptide Y level in patients with COPD was significantly higher than that in patients without COPD (130.36 ± 20.58 pg/ml vs 86.62 ± 13.02 pg/ml; t=10.201, p<0.01). Moreover, the levels in patients of the different stages (I, II, III) of COPD were significantly different from one another (F=20.334, p<0.01). Conclusion: the serum neuropeptide Y levels increased significantly in patients with COPD and were correlated to the different disease stages

  18. Localization of neuropeptide gene expression in larvae of an echinoderm, the starfish Asterias rubens

    Directory of Open Access Journals (Sweden)

    Tatiana D Mayorova

    2016-12-01

    Full Text Available Neuropeptides are an ancient class of neuronal signaling molecules that regulate a variety of physiological and behavioral processes in animals. The life cycle of many animals includes a larval stage(s that precedes metamorphic transition to a reproductively active adult stage but, with the exception of Drosophila melanogaster and other insects, research on neuropeptide signaling has hitherto largely focused on adult animals. However, recent advances in genome/transcriptome sequencing have facilitated investigation of neuropeptide expression/function in the larvae of protostomian (e.g. the annelid Platynereis dumerilii and deuterostomian (e.g. the urochordate Ciona intestinalis invertebrates. Accordingly, here we report the first multi-gene investigation of larval neuropeptide precursor expression in a species belonging to the phylum Echinodermata - the starfish Asterias rubens. Whole-mount mRNA in situ hybridization was used to visualize in bipinnaria and brachiolaria stage larvae the expression of eight neuropeptide precursors: L-type SALMFamide (S1, F-type SALMFamide (S2, vasopressin/oxytocin-type, NGFFYamide, thyrotropin-releasing hormone-type, gonadotropin-releasing hormone-type, calcitonin-type and corticotropin-releasing hormone-type. Expression of only three of the precursors (S1, S2, NGFFYamide was observed in bipinnaria larvae but by the brachiolaria stage expression of all eight precursors was detected. An evolutionarily conserved feature of larval nervous systems is the apical organ and in starfish larvae this comprises the bilaterally symmetrical lateral ganglia, but only the S1 and S2 precursors were found to be expressed in these ganglia. A prominent feature of brachiolaria larvae is the attachment complex, comprising the brachia and adhesive disk, which mediates larval attachment to a substratum prior to metamorphosis. Interestingly, all of the neuropeptide precursors examined here are expressed in the attachment complex, with

  19. Brain imaging during seizure: ictal brain SPECT

    International Nuclear Information System (INIS)

    Kottamasu, Sambasiva Rao

    1997-01-01

    The role of single photon computed tomography (SPECT) in presurgical localization of medically intractable complex partial epilepsy (CPE) in children is reviewed. 99m Technetium neurolite, a newer lipophylic agent with a high first pass brain extraction and little or no redistribution is injected during a seizure, while the child is monitored with a video recording and continuous EEG and SPECT imaging is performed in the next 1-3 hours with the images representing regional cerebral profusion at the time of injection. On SPECT studies performed with radiopharmaceutical injected during a seizure, ictal focus is generally hypervascular. Other findings on ictal brain SPECT include hypoperfusion of adjacent cerebral cortex and white matter, hyperperfusion of contralateral motor cortex, hyperperfusion of ipsilateral basal ganglia and thalamus, brain stem and contralateral cerebellum. Ictal brain SPECT is non-invasive, cost effective and highly sensitive for localization of epileptic focus in patients with intractable CPE. (author)

  20. Using imaging to target the prefrontal cortex for transcranial magnetic stimulation studies in treatment-resistant depression

    OpenAIRE

    Johnson, Kevin A.; Ramsey, Dave; Kozel, Frank A.; Bohning, Daryl E.; Anderson, Berry; Nahas, Ziad; Sacke?m, Harold A.; George, Mark S.

    2006-01-01

    Structural imaging studies of the brains of patients with treatment-resistant depression (TRD) have found several abnormalities, including smaller hippocampus, orbitofrontal cortex, or pre?frontal cortex. Transcranial magnetic stimulation (TMS) is a noninvasive means of modulating brain activity, and has shown antidepressant treatment efficacy. 1 The initial methods used for targeting the prefrontal cortex are most likely insufficient. Herwig et al found that a common rule-based approach (the...

  1. Prevention of Stress-Impaired Fear Extinction Through Neuropeptide S Action in the Lateral Amygdala

    OpenAIRE

    Chauveau, Frédéric; Lange, Maren Denise; Jüngling, Kay; Lesting, Jörg; Seidenbecher, Thomas; Pape, Hans-Christian

    2012-01-01

    Stressful and traumatic events can create aversive memories, which are a predisposing factor for anxiety disorders. The amygdala is critical for transforming such stressful events into anxiety, and the recently discovered neuropeptide S transmitter system represents a promising candidate apt to control these interactions. Here we test the hypothesis that neuropeptide S can regulate stress-induced hyperexcitability in the amygdala, and thereby can interact with stress-induced alterations of fe...

  2. The effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women

    OpenAIRE

    Khoshdel, Abolfazl; Kheiri, Soleiman; Nasiri, Jafar; Tehran, Hoda Ahmari; Heidarian, Esfandiar

    2014-01-01

    Background: Many pregnant Muslim women choose to fast during Ramadan every year worldwide. This study aimed to examine the effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women and find whether fasting during pregnancy could have a negative effect on the health of mothers and fetuses. Methods: This cross-sectional study was conducted on 39 healthy volunteer fasting pregnant women. Serum leptin, neuropeptide Y, insulin levels, body mass index and weight were m...

  3. Genomics and peptidomics of neuropeptides and protein hormones present in the parasitic wasp Nasonia vitripennis

    DEFF Research Database (Denmark)

    Hauser, Frank; Neupert, Susanne; Williamson, Michael

    2010-01-01

    Neuropeptides and protein hormones constitute a very important group of signaling molecules, regulating central physiological processes such as reproduction, development, and behavior. Using a bioinformatics approach, we screened the recently sequenced genome of the parasitic wasp, Nasonia vitrip...... melanogaster, Aedes aegypti (both Diptera), Bombyx mori (Lepidoptera), Tribolium castaneum (Coleoptera), Apis mellifera (Hymenoptera), and Acyrthosiphon pisum (Hemiptera). This lower number of neuropeptide genes might be related to Nasonia's parasitic life....

  4. Role of plasma neuropeptide Y in patients with different thyroid functional status

    International Nuclear Information System (INIS)

    Zhong Chongming

    2004-01-01

    Objective: To investigate the plasma neuropeptide Y levels in patients with different thyroid functional status (hypo, hyperthyroidism as well as euthyroid status). Methods: Plasma neuropeptide Y levels in 55 hyperthyroid patients, 47 hypothyroid patients and 57 euthyroid controls were measured with radioimmunoassay. Results: Plasma neuropeptide Y levels in hyperthyroid patients (71.5 ± 14.7) ng/L, were significantly higher than those in controls (71.5 ± 14.7) ng/L, (0.001< P<0.05). Plasma neuropeptide Y levels in hypothyroid patients (42.2 ± 24.3) ng/L were lower than those in controls (71.5 ± 14.7) ng/L, were significantly higher than those in hypothyroid patients (42.2 ± 24.3) ng/L; Plasma neuropeptide Y levels were negatively correlated with leptin levels in all samples (r=-0.58, P=0.015). Conclusion: Both neuropeptide Y and thyroid hormones were important factors of energy metabolism and they might work together to maintain encrgy balance. (authors)

  5. Grammatical distinctions in the left frontal cortex.

    Science.gov (United States)

    Shapiro, K A; Pascual-Leone, A; Mottaghy, F M; Gangitano, M; Caramazza, A

    2001-08-15

    Selective deficits in producing verbs relative to nouns in speech are well documented in neuropsychology and have been associated with left hemisphere frontal cortical lesions resulting from stroke and other neurological disorders. The basis for these impairments is unresolved: Do they arise because of differences in the way grammatical categories of words are organized in the brain, or because of differences in the neural representation of actions and objects? We used repetitive transcranial magnetic stimulation (rTMS) to suppress the excitability of a portion of left prefrontal cortex and to assess its role in producing nouns and verbs. In one experiment subjects generated real words; in a second, they produced pseudowords as nouns or verbs. In both experiments, response latencies increased for verbs but were unaffected for nouns following rTMS. These results demonstrate that grammatical categories have a neuroanatomical basis and that the left prefrontal cortex is selectively engaged in processing verbs as grammatical objects.

  6. An integrative theory of prefrontal cortex function.

    Science.gov (United States)

    Miller, E K; Cohen, J D

    2001-01-01

    The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed

  7. Monkey cortex through fMRI glasses.

    Science.gov (United States)

    Vanduffel, Wim; Zhu, Qi; Orban, Guy A

    2014-08-06

    In 1998 several groups reported the feasibility of fMRI experiments in monkeys, with the goal to bridge the gap between invasive nonhuman primate studies and human functional imaging. These studies yielded critical insights in the neuronal underpinnings of the BOLD signal. Furthermore, the technology has been successful in guiding electrophysiological recordings and identifying focal perturbation targets. Finally, invaluable information was obtained concerning human brain evolution. We here provide a comprehensive overview of awake monkey fMRI studies mainly confined to the visual system. We review the latest insights about the topographic organization of monkey visual cortex and discuss the spatial relationships between retinotopy and category- and feature-selective clusters. We briefly discuss the functional layout of parietal and frontal cortex and continue with a summary of some fascinating functional and effective connectivity studies. Finally, we review recent comparative fMRI experiments and speculate about the future of nonhuman primate imaging. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. [Neuroanatomy of Frontal Association Cortex].

    Science.gov (United States)

    Takada, Masahiko

    2016-11-01

    The frontal association cortex is composed of the prefrontal cortex and the motor-related areas except the primary motor cortex (i.e., the so-called higher motor areas), and is well-developed in primates, including humans. The prefrontal cortex receives and integrates large bits of diverse information from the parietal, temporal, and occipital association cortical areas (termed the posterior association cortex), and paralimbic association cortical areas. This information is then transmitted to the primary motor cortex via multiple motor-related areas. Given these facts, it is likely that the prefrontal cortex exerts executive functions for behavioral control. The functional input pathways from the posterior and paralimbic association cortical areas to the prefrontal cortex are classified primarily into six groups. Cognitive signals derived from the prefrontal cortex are conveyed to the rostral motor-related areas to transform them into motor signals, which finally enter the primary motor cortex via the caudal motor-related areas. Furthermore, it has been shown that, similar to the primary motor cortex, areas of the frontal association cortex form individual networks (known as "loop circuits") with the basal ganglia and cerebellum via the thalamus, and hence are extensively involved in the expression and control of behavioral actions.

  9. Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats.

    OpenAIRE

    Schubring-Giese Maximilian; Leemburg Susan; Luft Andreas Rüdiger; Hosp Jonas Aurel

    2016-01-01

    Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of ...

  10. Neuropeptide Y in Alcohol Addiction and Affective Disorders

    Directory of Open Access Journals (Sweden)

    Annika Thorsell

    2017-07-01

    Full Text Available Neuropeptide Y (NPY, a neuropeptide highly conserved throughout evolution, is present at high levels in the central nervous system (CNS, as well as in peripheral tissues such as the gut and cardiovascular system. The peptide exerts its effects via multiple receptor subtypes, all belonging to the G-protein-coupled receptor superfamily. Of these subtypes, the Y1 and the Y2 are the most thoroughly characterized, followed by the Y5 subtype. NPY and its receptors have been shown to be of importance in central regulation of events underlying, for example, affective disorders, drug/alcohol use disorders, and energy homeostasis. Furthermore, within the CNS, NPY also affects sleep regulation and circadian rhythm, memory function, tissue growth, and plasticity. The potential roles of NPY in the etiology and pathophysiology of mood and anxiety disorders, as well as alcohol use disorders, have been extensively studied. This focus was prompted by early indications for an involvement of NPY in acute responses to stress, and, later, also data pointing to a role in alterations within the CNS during chronic, or repeated, exposure to adverse events. These functions of NPY, in addition to the peptide’s regulation of disease states, suggest that modulation of the activity of the NPY system via receptor agonists/antagonists may be a putative treatment mechanism in affective disorders as well as alcohol use disorders. In this review, we present an overview of findings with regard to the NPY system in relation to anxiety and stress, acute as well as chronic; furthermore we discuss post-traumatic stress disorder and, in part depression. In addition, we summarize findings on alcohol use disorders and related behaviors. Finally, we briefly touch upon genetic as well as epigenetic mechanisms that may be of importance for NPY function and regulation. In conclusion, we suggest that modulation of NPY-ergic activity within the CNS, via ligands aimed at different receptor

  11. [Raman spectra of monkey cerebral cortex tissue].

    Science.gov (United States)

    Zhu, Ji-chun; Guo, Jian-yu; Cai, Wei-ying; Wang, Zu-geng; Sun, Zhen-rong

    2010-01-01

    Monkey cerebral cortex, an important part in the brain to control action and thought activities, is mainly composed of grey matter and nerve cell. In the present paper, the in situ Raman spectra of the cerebral cortex of the birth, teenage and aged monkeys were achieved for the first time. The results show that the Raman spectra for the different age monkey cerebral cortex exhibit most obvious changes in the regions of 1000-1400 and 2800-3000 cm(-1). With monkey growing up, the relative intensities of the Raman bands at 1313 and 2885 cm(-1) mainly assigned to CH2 chain vibrational mode of lipid become stronger and stronger whereas the relative intensities of the Raman bands at 1338 and 2932 cm(-1) mainly assigned to CH3 chain vibrational mode of protein become weaker and weaker. In addition, the two new Raman bands at 1296 and 2850 cm(-1) are only observed in the aged monkey cerebral cortex, therefore, the two bands can be considered as a character or "marker" to differentiate the caducity degree with monkey growth In order to further explore the changes, the relative intensity ratios of the Raman band at 1313 cm(-1) to that at 1338 cm(-1) and the Raman band at 2885 cm(-1) to that at 2 932 cm(-1), I1313/I1338 and I2885/I2932, which are the lipid-to-protein ratios, are introduced to denote the degree of the lipid content. The results show that the relative intensity ratios increase significantly with monkey growth, namely, the lipid content in the cerebral cortex increases greatly with monkey growth. So, the authors can deduce that the overmuch lipid is an important cause to induce the caducity. Therefore, the results will be a powerful assistance and valuable parameter to study the order of life growth and diagnose diseases.

  12. Live Imaging of Mitosis in the Developing Mouse Embryonic Cortex

    OpenAIRE

    Pilaz, Louis-Jan; Silver, Debra L.

    2014-01-01

    Although of short duration, mitosis is a complex and dynamic multi-step process fundamental for development of organs including the brain. In the developing cerebral cortex, abnormal mitosis of neural progenitors can cause defects in brain size and function. Hence, there is a critical need for tools to understand the mechanisms of neural progenitor mitosis. Cortical development in rodents is an outstanding model for studying this process. Neural progenitor mitosis is commonly examined in fixe...

  13. Distribution of nitric oxide synthase and neuropeptide Y neurones during the development of the hippocampal formation in the rat.

    Science.gov (United States)

    Moryś, Joanna M; Kowiański, Przemysław; Moryś, Janusz

    2002-01-01

    Nitric oxide (NO) is a short-lived radical, which modulates synaptic plasticity, neuronal oscillations and cerebral blood flow. NOS-containing neurones can be detected anatomically by nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry or by NOS immunohistochemistry. Neuropeptide Y(NPY) is the most abundant peptide in the brain. NPY is connected with several vital functions, such as a feeding behaviour, sexual maturation, regulation of circadian rhythms, body temperature, blood pressure and neuroendocrine secretions. Neuropeptide Y also modulates anxiety-related disorders, limbic epileptic seizures as well as learning and memory processes. The study was performed on 45 Wistar rats of various ages (PO, P4, P7, P10, P14, P21, P30, P60, and P120; P--postnatal day). The free-floating sections were stained with standard immunohistochemistry methods. Thereafter the histological sections were studied using the confocal laser microscope equipped. For 3D reconstruction the image analysis program LaserSharp 2000v. 2.0 (Bio-Rad, UK) was used. We found that in the newborn rat both NOS- and NPY-immunoreactivity was weak. It had been increasing gradually until the 7th day of postnatal life, after that until P14 it was maintained on the similar level, and then the number of immunolabelled cells deceased. The developmental changes concerned cell morphology as well--until the 10th day of life the immunoreactive cells were immature, with round or oval bodies and had only a few fibres. From P14 the cells' morphology became similar to that in adult.

  14. The Role of the Neuropeptide Somatostatin on Methamphetamine and Glutamate-Induced Neurotoxicity in the Striatum of Mice

    Science.gov (United States)

    Afanador, Lauriaselle; Mexhitaj, Ina; Diaz, Carolyn; Ordonez, Dalila; Baker, Lisa; Angulo, Jesus A.

    2014-01-01

    A large body of evidence shows that methamphetamine (METH) causes sustained damage to the brain in animal models and human METH users. In chronic users there are indications of cognitive and motor deficits. Striatal neuropeptides are in a position to modulate the neurochemical effects of METH and consequently striatal neural damage. Somatostatin (SST) is an intrinsic striatal neuropeptide that has been shown to inhibit glutamate transmission; glutamate is integral to METH toxicity and contributes to nitric oxide (NO) synthesis. We hypothesize that SST will protect from METH by inhibition of NO synthesis and thus reducing oxidative stress. To this end, the SST analogue octreotide (OCT) was microinjected into the striatum prior to a systemic injection of METH (30 mg/kg). We then assessed 3-nitrotyrosine (3-NT), an indirect index of NO production, tyrosine hydroxylase (TH) protein levels (dopamine terminal marker) and Fluoro-Jade C positive cells (degenerating cells). The SST agonist OCT dose dependently attenuated the METH-induced accumulation of striatal 3-NT. Moreover, pretreatment with OCT effectively mitigated cell death but failed to protect dopamine terminals. Next we co-infused OCT and NMDA and measured 3-NT and Fluoro-Jade C staining. Treatment with OCT had no effect on these parameters. The data demonstrate that SST attenuates the METH-induced production of NO protecting the striatum from the METH-induced cell loss. However, SST failed to prevent the toxicity of the dopamine terminals suggesting that pre- and post-synaptic striatal damage occur via independent mechanisms. PMID:23524190

  15. Morphological and functional correlates of VIP neurons in cerebral cortex

    International Nuclear Information System (INIS)

    Magistretti, P.J.; Morrison, J.H.; Shoemaker, W.J.; Bloom, F.E.

    1984-01-01

    Vasoactive Intestinal Polypeptide (VIP) promotes the hydrolysis of 3H-glycogen newly synthesized from 3H-glucose by mouse cortical slices. This effect occurs rapidly, approximately 50% of the maximal effect being reached within one minute. The maximal effect is achieved after 5 minutes and maintained for at least 25 minutes. Furthermore the glycogenolytic effect of VIP is reversible, and pharmacologically specific. Thus several neuropeptides present in cerebral cortex such as cholecystokinin-8, somatostatin-28, somatostatin-14, met-enkephalin, leu-enkephalin, do not affect 3H-glycogen levels. VIP fragments 6-28, 16-28 and 21-28 are similarly inactive. Furthermore, among the peptides which share structural homologies with VIP, such as glucagon, secretin, PHI-27 and Gastric Inhibitory Peptide, only secretin and PHI-27 promote 3H-glycogen hydrolysis, with EC50 of 500 and 300 nM respectively, compared to an EC50 of 25 nM for VIP. Immunohistochemical observations indicate that each VIP-containing bipolar cell is identified with a unique radical cortical volume, which is generally between 15-60 micrograms in diameter and overlaps with the contiguous domains of neighbouring VIP-containing bipolar cells. Thus this set of biochemical and morphological observations support the notion that VIP neurons have the capacity to regulate the availability of energy substrates in cerebral cortex locally, within circumscribed, contiguous, radial domains

  16. Extending the scope of neuropeptidomics in the mammalian brain

    Directory of Open Access Journals (Sweden)

    Xiaozhe Zhang

    2014-06-01

    Full Text Available Neuropeptides are signaling molecules of intermediate size that are involved in neurotransmission and endocrine regulation. Complete monitoring of neuropeptides using neuropeptidomics approaches remains an important goal for describing targeted physiological regulation pathways. Considerable effort has been expended, particularly in terms of technique and methodology development, to extend the scope of neuropeptidomics. The capability of peptide characterization has been gradually improved, thus responding to increasing demands for broad detection and determination of various peptides. In this review, we discuss some achievements for the improvement of peptide identification coverage and their application for brain diseases and studying consequences of drug applications.

  17. Auditory cortex involvement in emotional learning and memory.

    Science.gov (United States)

    Grosso, A; Cambiaghi, M; Concina, G; Sacco, T; Sacchetti, B

    2015-07-23

    Emotional memories represent the core of human and animal life and drive future choices and behaviors. Early research involving brain lesion studies in animals lead to the idea that the auditory cortex participates in emotional learning by processing the sensory features of auditory stimuli paired with emotional consequences and by transmitting this information to the amygdala. Nevertheless, electrophysiological and imaging studies revealed that, following emotional experiences, the auditory cortex undergoes learning-induced changes that are highly specific, associative and long lasting. These studies suggested that the role played by the auditory cortex goes beyond stimulus elaboration and transmission. Here, we discuss three major perspectives created by these data. In particular, we analyze the possible roles of the auditory cortex in emotional learning, we examine the recruitment of the auditory cortex during early and late memory trace encoding, and finally we consider the functional interplay between the auditory cortex and subcortical nuclei, such as the amygdala, that process affective information. We conclude that, starting from the early phase of memory encoding, the auditory cortex has a more prominent role in emotional learning, through its connections with subcortical nuclei, than is typically acknowledged. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Forelimb training drives transient map reorganization in ipsilateral motor cortex.

    Science.gov (United States)

    Pruitt, David T; Schmid, Ariel N; Danaphongse, Tanya T; Flanagan, Kate E; Morrison, Robert A; Kilgard, Michael P; Rennaker, Robert L; Hays, Seth A

    2016-10-15

    Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Conflict processing in the anterior cingulate cortex constrains response priming.

    Science.gov (United States)

    Pastötter, Bernhard; Hanslmayr, Simon; Bäuml, Karl-Heinz T

    2010-05-01

    A prominent function of the anterior cingulate cortex (ACC) is to process conflict between competing response options. In this study, we investigated the role of conflict processing in a response-priming task in which manual responses were either validly or invalidly cued. Examining electrophysiological measurements of oscillatory brain activity on the source level, we found response priming to be related to a beta power decrease in the premotor cortex and conflict processing to be linked to a theta power increase in the ACC. In particular, correlation of oscillatory brain activities in the ACC and the premotor cortex showed that conflict processing reduces response priming by slowing response time in valid trials and lowering response errors in invalid trials. This relationship emerged on a between subjects level as well as within subjects, on a single trial level. These findings suggest that conflict processing in the ACC constrains the automatic priming process. 2010 Elsevier Inc. All rights reserved.

  20. Altered intrinsic connectivity of the auditory cortex in congenital amusia.

    Science.gov (United States)

    Leveque, Yohana; Fauvel, Baptiste; Groussard, Mathilde; Caclin, Anne; Albouy, Philippe; Platel, Hervé; Tillmann, Barbara

    2016-07-01

    Congenital amusia, a neurodevelopmental disorder of music perception and production, has been associated with abnormal anatomical and functional connectivity in a right frontotemporal pathway. To investigate whether spontaneous connectivity in brain networks involving the auditory cortex is altered in the amusic brain, we ran a seed-based connectivity analysis, contrasting at-rest functional MRI data of amusic and matched control participants. Our results reveal reduced frontotemporal connectivity in amusia during resting state, as well as an overconnectivity between the auditory cortex and the default mode network (DMN). The findings suggest that the auditory cortex is intrinsically more engaged toward internal processes and less available to external stimuli in amusics compared with controls. Beyond amusia, our findings provide new evidence for the link between cognitive deficits in pathology and abnormalities in the connectivity between sensory areas and the DMN at rest. Copyright © 2016 the American Physiological Society.

  1. Plasma neuropeptide Y levels differ in distinct diabetic conditions.

    Science.gov (United States)

    Ilhan, Aysegül; Rasul, Sazan; Dimitrov, Alexander; Handisurya, Ammon; Gartner, Wolfgang; Baumgartner-Parzer, Sabina; Wagner, Ludwig; Kautzky-Willer, Alexandra; Base, Wolfgang

    2010-12-01

    Neuropeptide Y (NPY) is an important hormone in appetite regulation. Although the contribution of NPY to metabolic disease has been previously demonstrated, there are only a few reports addressing NPY plasma levels under distinct diabetic conditions. In this study we evaluated NPY plasma levels in diabetes mellitus type 2 (DM2) patients with (n=34) and without (n=34) diabetic polyneuropathy (PNP) and compared these with age and gender matched healthy controls (n=34). We also analyzed NPY plasma levels in gestational diabetes mellitus (GDM) patients with age and pregnancy-week matched controls with normal glucose tolerance (NGT). NPY concentration was determined using a commercially available radioimmunoassay kit. In addition, metabolic parameters of DM2 and GDM patients were recorded. One-way ANOVA tests with appropriate post hoc corrections showed elevated levels of NPY in DM2 patients with and without PNP when compared with those of healthy controls (122.32±40.86 and 117.33±29.92 vs. 84.65±52.17 pmol/L; pwomen with NGT (74.87±14.36 vs. 84.82±51.13 pmol/L, respectively). Notably, the NPY concentration correlated positively with insulin levels in DM2 patients (R=0.35, pDM2 pathology. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Neuropeptides as endogenous neuronal growth regulatory factors on serotonergic maturation

    International Nuclear Information System (INIS)

    Davila-Garcia, M.I.

    1989-01-01

    Products of the proopiomelanocortin molecule as well as leu- and met-enkephalin were tested for their effects on serotonergic neuronal maturation. High affinity uptake of ( 3 H)5-HT and morphometrics using immunocytochemistry specific for serotonergic neurons were used to monitor neuronal maturation. Cultured brainstem raphe neurons from 14 day fetuses, in the presence or absence of target tissue, were administered neuropeptides at various concentrations for 1,3 or 5 days in culture. ACTH peptides stimulate neurite length and, with the endorphins, the expression of ( 3 H)5-HT uptake by serotonergic fetal neurons cultured alone but had no effect when these neurons were cocultured with hippocampal target cells. A daily dose of leu-enkephalin to these cells inhibited neuronal uptake after 5 days of exposure and decreased neurite cell length in 24 hr cultures. In contrast, a single dose of leu-enkephalin at plating stimulated uptake after 5 days while co-administration of bacitracin inhibited uptake expression. Naloxone reversed the opioid effect and stimulated uptake when administered alone. Desulfated-CCK, which resembles leu-enkephalin, was equally potent as leu-enkephalin in inhibiting uptake

  3. Neuropeptides as endogenous neuronal growth regulatory factors on serotonergic maturation

    Energy Technology Data Exchange (ETDEWEB)

    Davila-Garcia, M.I.

    1989-01-01

    Products of the proopiomelanocortin molecule as well as leu- and met-enkephalin were tested for their effects on serotonergic neuronal maturation. High affinity uptake of ({sup 3}H)5-HT and morphometrics using immunocytochemistry specific for serotonergic neurons were used to monitor neuronal maturation. Cultured brainstem raphe neurons from 14 day fetuses, in the presence or absence of target tissue, were administered neuropeptides at various concentrations for 1,3 or 5 days in culture. ACTH peptides stimulate neurite length and, with the endorphins, the expression of ({sup 3}H)5-HT uptake by serotonergic fetal neurons cultured alone but had no effect when these neurons were cocultured with hippocampal target cells. A daily dose of leu-enkephalin to these cells inhibited neuronal uptake after 5 days of exposure and decreased neurite cell length in 24 hr cultures. In contrast, a single dose of leu-enkephalin at plating stimulated uptake after 5 days while co-administration of bacitracin inhibited uptake expression. Naloxone reversed the opioid effect and stimulated uptake when administered alone. Desulfated-CCK, which resembles leu-enkephalin, was equally potent as leu-enkephalin in inhibiting uptake.

  4. Mast cell subsets and neuropeptides in leprosy reactions

    Directory of Open Access Journals (Sweden)

    Antunes Sérgio Luiz Gomes

    2003-01-01

    Full Text Available The immunohistochemical identification of neuropeptides (calcitonin gene-related peptide, vasoactive intestinal polypeptide, substance P, alpha-melanocyte stimulating hormone and gamma-melanocyte stimulating hormone quantification of mast cells and their subsets (tryptase/chymase-immunoreactive mast cells = TCMC and tryptase-immunoreactive mast cells = TMC were determined in biopsies of six patients with leprosy reactions (three patients with type I reaction and three with type II. Biopsies were compared with those taken from the same body site in the remission stage of the same patient. We found a relative increase of TMC in the inflammatory infiltrate of the reactional biopsies compared to the post-reactional biopsy. Also, the total number of mast cells and the TMC/TCMC ratio in the inflammatory infiltrate was significantly higher than in the intervening dermis of the biopsies of both periods. No significant difference was found regarding neuroptide expression in the reactional and post-reactional biopsies. The relative increase of TMC in the reactional infiltrates could implicate this mast cell subset in the reported increase of the immune response in leprosy reactions.

  5. Electropuncture influences on learning, memory, and neuropeptide expression in a rat model of vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Ying Shao; Yanqian Fu; Lihua Qiu; Bing Yan; Xinsheng Lai; Chunzhi Tang

    2008-01-01

    BACKGROUND: Studies in recent years have indicated that several neuropeptide-like substances, such as arginine vasopressin (AVP), somatostatin (SS), and β-endorphine (β-EP), are involved in the process of cerebral ischemic damage to cranial nerves.OBJECTIVE: To observe the effects of electropuncture on back-shu points, as well as the influence on learning and memory, AVP, SS, and β-EP levels in plasma and brain were measured in a rat model of vascular dementia (VD). DESIGN: Randomized controlled trial.SETTING: College of Acupuncture and Massage of Guangzhou University of Chinese Medicine.MATERIALS: This experiment was performed at the Animal Experiment Center of Guangzhou University of TCM from December 2005 to December 2006. A total of 48 healthy adult male Sprague Dawley rats of SPF-grade, 180-220 g, were provided by The Animal Experiment Center of Guangzhou University of Traditional Chinese Medicine. The following instruments were used: SDQ-30 Dipolar Radio-frequency Electrocoagulator (Shanghai Operation Instrument Factory), Morris Water Maze (The Animal Experiment Center of Guangzhou University of Traditional Chinese Medicine), Type G6805-1 Treating Equipment (Huasheng Equipment Factory, Qingdao, China).METHODS: ① Eight rats were randomly selected for the control group; the remaining 40 rats underwent 4-vascular occlusion to establish a cerebral ischemia model. Due to the death of 13 rats and 2 hemiplegies during model establishment, there was a total of 25 model rats available for testing. The model rats were divided randomly into 3 groups according to their body weight: electropuncture group (n = 9), medication group (n = 8), and VD group (n = 8). ② Electropuncture group: 25 mm needles (28 gauge) were used to electropuncture (150 Hz, continuous waves, 1.0-2.0 mA, duration of 20 minutes) the following acupoints: Baihui (GV20), Geshu (BL17), Pishu (BL20), and Shenshu (BL23). The acupoints were located according to Experimental acupuncturology and were

  6. Orbitofrontal cortex contribution to working memory. N-back ERP study

    International Nuclear Information System (INIS)

    Nakao, Yoshiaki; Tamura, Toshiyo; Kodabashi, Atsushi; Fujimoto, Toshiro; Yarita, Masaru

    2011-01-01

    Remarkable progress in cognitive neuroscience has revealed the involvement of the prefrontal cortex and the orbitofrontal cortex in human working memory, but the orbitofrontal cortex is still one of the least understood regions in the human brain. To elucidate the contribution of the orbitofrontal cortex to human working memory, we studied electroencephalography (EEG) P300 activity in n-back task. We elicited early P3 around 300 ms and late P3 around 360 ms of P300 components in n-back event related potentials (ERP). The amplitudes of the respective peaks changed depending on the working memory load (0-back, 1-back, 2-back, 3-back). We used source analysis to evaluate the orbitofrontal cortex in P3 components. A source model was constructed with the sources seeded from fMRI meta-analysis of n-back task and additional sources in the orbitofrontal cortex and the visual cortex estimated with P100 and late P3 components in the n-back ERP. This source model had more than 99% of GOF (goodness of fit) in n-back ERP. It gave us an insight of brain activity at the positions where sources existed. Early P3 was mainly produced by the dorsolateral prefrontal cortex, the ventrolateral prefrontal cortex, the inferior parietal lobule, the medial posterior parietal and the visual cortex. Late P3 was mainly produced by the medial premotor, the lateral premotor, the frontal pole and the orbitofrontal cortex. The contribution of the frontal pole and the orbitofrontal cortex had peaks around 390 ms which were later than late P3 component. In this study, the method to evaluate the orbitofrontal cortex activity in n-back ERP was provided. Our results elicited the involvement of the orbitofrontal cortex in late P3 component of n-back ERP. (author)

  7. khat distorts the prefrontal cortex histology and function of adult

    African Journals Online (AJOL)

    2018-02-28

    Feb 28, 2018 ... It affects many brain centers including the prefrontal cortex which is the ... cognitive behaviors however; it is linked to many psychological ... by traumatic events while others experience ... scientific research in exposing the effects. ... between 3 to 5pm daily. ... needle attached a plastic tubing was connected.

  8. Comparison of (stereotactic) parcellations in mouse prefrontal cortex

    NARCIS (Netherlands)

    van de Werd, H.J.J.M.; Uylings, H.B.M.

    2014-01-01

    This study compares the cytoarchitectonic parcellation of the prefrontal cortex (PFC) in the mouse as presented in publications that are commonly used for identifying brain areas. Agreement was found to be greater for boundaries in the medial PFC than in the lateral PFC and lowest for those in the

  9. Transcranial magnetic stimulation and the human brain

    Science.gov (United States)

    Hallett, Mark

    2000-07-01

    Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non-invasive tool for studying the human brain. A pulsed magnetic field creates current flow in the brain and can temporarily excite or inhibit specific areas. TMS of motor cortex can produce a muscle twitch or block movement; TMS of occipital cortex can produce visual phosphenes or scotomas. TMS can also alter the functioning of the brain beyond the time of stimulation, offering potential for therapy.

  10. A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder.

    Science.gov (United States)

    Sayed, Sehrish; Van Dam, Nicholas T; Horn, Sarah R; Kautz, Marin M; Parides, Michael; Costi, Sara; Collins, Katherine A; Iacoviello, Brian; Iosifescu, Dan V; Mathé, Aleksander A; Southwick, Steven M; Feder, Adriana; Charney, Dennis S; Murrough, James W

    2018-01-01

    Anxiety and trauma-related disorders are among the most prevalent and disabling medical conditions in the United States, and posttraumatic stress disorder in particular exacts a tremendous public health toll. We examined the tolerability and anxiolytic efficacy of neuropeptide Y administered via an intranasal route in patients with posttraumatic stress disorder. Twenty-six individuals were randomized in a cross-over, single ascending dose study into 1 of 5 cohorts: 1.4 mg (n=3), 2.8 mg (n=6), 4.6 mg (n=5), 6.8 mg (n=6), and 9.6 mg (n=6). Each individual was dosed with neuropeptide Y or placebo on separate treatment days 1 week apart in random order under double-blind conditions. Assessments were conducted at baseline and following a trauma script symptom provocation procedure subsequent to dosing. Occurrence of adverse events represented the primary tolerability outcome. The difference between treatment conditions on anxiety as measured by the Beck Anxiety Inventory and the State-Trait Anxiety Inventory immediately following the trauma script represented efficacy outcomes. Twenty-four individuals completed both treatment days. Neuropeptide Y was well tolerated up to and including the highest dose. There was a significant interaction between treatment and dose; higher doses of neuropeptide Y were associated with a greater treatment effect, favoring neuropeptide Y over placebo on Beck Anxiety Inventory score (F1,20=4.95, P=.038). There was no significant interaction for State-Trait Anxiety Inventory score. Our study suggests that a single dose of neuropeptide Y is well tolerated up to 9.6 mg and may be associated with anxiolytic effects. Future studies exploring the safety and efficacy of neuropeptide Y in stress-related disorders are warranted. The reported study is registered at: http://clinicaltrials.gov (ID: NCT01533519). © The Author(s) 2017. Published by Oxford University Press on behalf of CINP.

  11. mammalian brain system

    Directory of Open Access Journals (Sweden)

    Alan Kania

    2014-06-01

    Full Text Available Relaxin-3, a member of the relaxin peptide family, was discovered in 2001 as a homologue of relaxin – a well-known reproductive hormone. However, it is the brain which turned out to be a major expression site of this newly discovered peptide. Both its molecular structure and expression pattern were shown to be very conserved among vertebrates. Extensive research carried out since the discovery of relaxin-3 contributed to the significant progress in our knowledge regarding this neuropeptide. The endogenous relaxin-3 receptor (RXFP3 was identified and the anatomy of the yet uncharacterized mammalian brain system was described, with nucleus incertus as the main center of relaxin-3 expression. Not only its diffusive projections throughout the whole brain, which reach various brain structures such as the hippocampus, septum, intergeniculate leaflet or amygdala, but also functional studies of the relaxin-3/RXFP3 signaling system, allowed this brain network to be classified as one of the ascending nonspecific brain systems. Thus far, research depicts the connection of relaxin-3 with phenomena such as feeding behavior, spatial memory, sleep/wake cycle or modulation of pituitary gland hormone secretion. Responsiveness of relaxin-3 neurons to stress factors and the strong orexigenic effect exerted by this peptide suggest its participation in modulation of feeding by stress, in particular of the chronic type. The discovery of relaxin-3 opened a new research field which will contribute to our better understanding of the neurobiological basis of feeding disorders.

  12. MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject

    Directory of Open Access Journals (Sweden)

    Andreas A Ioannides

    2013-08-01

    Full Text Available Cross-modal activity in visual cortex of blind subjects has been reported during performance of variety of non-visual tasks. A key unanswered question is through which pathways non-visual inputs are funneled to the visual cortex. Here we used tomographic analysis of single trial magnetoencephalography (MEG data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified reproducible brain responses in the primary somatosensory (S1 and motor (M1 cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45 to 70 Hz activity at latencies of 20 to 50 ms in S1 and M1, and posterior parietal cortex Brodmann areas (BA 7 and 40, which compared to lower frequencies, were substantially more pronounced in the blind than the sighted subjects. Critically, at frequencies from α-band up to 100 Hz we found clear, strong and widespread responses in the visual cortex of the blind subject, which increased with the intensity of the somatosensory stimuli. Time-delayed mutual information (MI revealed that in blind subject the stimulus information is funneled from the early somatosensory to visual cortex through posterior parietal BA 7 and 40, projecting first to visual areas V5 and V3, and eventually V1. The flow of information through this pathway occured in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first evidence from MEG that in blind subjects, tactile information is routed from primary somatosensory to occipital cortex via the posterior parietal cortex.

  13. MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject.

    Science.gov (United States)

    Ioannides, Andreas A; Liu, Lichan; Poghosyan, Vahe; Saridis, George A; Gjedde, Albert; Ptito, Maurice; Kupers, Ron

    2013-01-01

    Cross-modal activity in visual cortex of blind subjects has been reported during performance of variety of non-visual tasks. A key unanswered question is through which pathways non-visual inputs are funneled to the visual cortex. Here we used tomographic analysis of single trial magnetoencephalography (MEG) data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified reproducible brain responses in the primary somatosensory (S1) and motor (M1) cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45-70 Hz activity at latencies of 20-50 ms in S1 and M1, and posterior parietal cortex Brodmann areas (BA) 7 and 40, which compared to lower frequencies, were substantially more pronounced in the blind than the sighted subjects. Critically, at frequencies from α-band up to 100 Hz we found clear, strong, and widespread responses in the visual cortex of the blind subject, which increased with the intensity of the somatosensory stimuli. Time-delayed mutual information (MI) revealed that in blind subject the stimulus information is funneled from the early somatosensory to visual cortex through posterior parietal BA 7 and 40, projecting first to visual areas V5 and V3, and eventually V1. The flow of information through this pathway occurred in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first evidence from MEG that in blind subjects, tactile information is routed from primary somatosensory to occipital cortex via the posterior parietal cortex.

  14. The Role of Medial Frontal Cortex in Action Anticipation in Professional Badminton Players.

    Science.gov (United States)

    Xu, Huan; Wang, Pin; Ye, Zhuo'er; Di, Xin; Xu, Guiping; Mo, Lei; Lin, Huiyan; Rao, Hengyi; Jin, Hua

    2016-01-01

    Some studies show that the medial frontal cortex is associated with more skilled action anticipation, while similar findings are not observed in some other studies, possibly due to the stimuli employed and the participants used as the control group. In addition, no studies have investigated whether there is any functional connectivity between the medial frontal cortex and other brain regions in more skilled action anticipation. Therefore, the present study aimed to re-investigate how the medial frontal cortex is involved in more skilled action anticipation by circumventing the limitations of previous research and to investigate that the medial frontal cortex functionally connected with other brain regions involved in action processing in more skilled action anticipation. To this end, professional badminton players and novices were asked to anticipate the landing position of the shuttlecock while watching badminton match videos or to judge the gender of the players in the matches. The video clips ended right at the point that the shuttlecock and the racket came into contact to reduce the effect of information about the trajectory of the shuttlecock. Novices who lacked training and watching experience were recruited for the control group to reduce the effect of sport-related experience on the medial frontal cortex. Blood oxygenation level-dependent activation was assessed by means of functional magnetic resonance imaging. Compared to novices, badminton players exhibited stronger activation in the left medial frontal cortex during action anticipation and greater functional connectivity between left medial frontal cortex and some other brain regions (e.g., right posterior cingulate cortex). Therefore, the present study supports the position that the medial frontal cortex plays a role in more skilled action anticipation and that there is a specific brain network for more skilled action anticipation that involves right posterior cingulate cortex, right fusiform gyrus

  15. The Role of Medial Frontal Cortex in Action Anticipation in Professional Badminton Players

    Science.gov (United States)

    Xu, Huan; Wang, Pin; Ye, Zhuo’er; Di, Xin; Xu, Guiping; Mo, Lei; Lin, Huiyan; Rao, Hengyi; Jin, Hua

    2016-01-01

    Some studies show that the medial frontal cortex is associated with more skilled action anticipation, while similar findings are not observed in some other studies, possibly due to the stimuli employed and the participants used as the control group. In addition, no studies have investigated whether there is any functional connectivity between the medial frontal cortex and other brain regions in more skilled action anticipation. Therefore, the present study aimed to re-investigate how the medial frontal cortex is involved in more skilled action anticipation by circumventing the limitations of previous research and to investigate that the medial frontal cortex functionally connected with other brain regions involved in action processing in more skilled action anticipation. To this end, professional badminton players and novices were asked to anticipate the landing position of the shuttlecock while watching badminton match videos or to judge the gender of the players in the matches. The video clips ended right at the point that the shuttlecock and the racket came into contact to reduce the effect of information about the trajectory of the shuttlecock. Novices who lacked training and watching experience were recruited for the control group to reduce the effect of sport-related experience on the medial frontal cortex. Blood oxygenation level-dependent activation was assessed by means of functional magnetic resonance imaging. Compared to novices, badminton players exhibited stronger activation in the left medial frontal cortex during action anticipation and greater functional connectivity between left medial frontal cortex and some other brain regions (e.g., right posterior cingulate cortex). Therefore, the present study supports the position that the medial frontal cortex plays a role in more skilled action anticipation and that there is a specific brain network for more skilled action anticipation that involves right posterior cingulate cortex, right fusiform gyrus

  16. Oxytocin and Estrogen Receptor β in the Brain: An Overview

    OpenAIRE

    Acevedo-Rodriguez, Alexandra; Mani, Shaila K.; Handa, Robert J.

    2015-01-01

    Oxytocin is a neuropeptide synthesized primarily by neurons of the paraventricular and supraoptic nuclei of the hypothalamus. These neurons have axons that project into the posterior pituitary and release oxytocin into the bloodstream to promote labor and lactation; however, oxytocin neurons also project to other brain areas where it plays a role in numerous brain functions. Oxytocin binds to the widely expressed oxytocin receptor, and, in doing so, it regulates homeostatic processes, social ...

  17. cDNA cloning and sequence determination of the pheromone biosynthesis activating neuropeptide from the seabuckthorn carpenterworm, Holcocerus hippophaecolus (Lepidoptera: Cossidae).

    Science.gov (United States)

    Li, Juan; Zhou, Jiao; Sun, Rongbo; Zhang, Haolin; Zong, Shixiang; Luo, Youqing; Sheng, Xia; Weng, Qiang

    2013-04-01

    The PBAN (pheromone biosynthesis activating neuropeptide)/pyrokinin peptides comprise a major neuropeptide family characterized by a common FXPRL amide at the C-terminus. These peptides are actively involved in many essential endocrine functions. For the first time, we reported the cDNA cloning and sequence determination of the PBAN from the seabuckthorn carpenterworm, Holcocerus hippophaecolus, by using rapid amplification of cDNA ends. The full-length cDNA of Hh-DH-PBAN contained five peptides: diapause hormone (DH) homolog, α-neuropeptide (NP), β-NP, PBAN, and γ-NP. All of the peptides were amidated at their C-terminus and shared a conserved motif, FXPR (or K) L. Moreover, Hh-DH-PBAN had high homology to the other members of the PBAN peptide family: 56% with Manduca sexta, 66% with Bombyx mori, 77% with Helicoverpa zea, and 47% with Plutella xylostella. Phylogenetic analysis revealed that Hh-DH-PBAN was closely related to PBANs from Noctuidae, demonstrated by the relatively higher similarity compared with H. zea. In addition, real-time quantitative PCR (qRT-PCR) analysis showed that Hh-DH-PBAN mRNA expression peaked in the brain-subesophageal ganglion (Br-SOG) complex, and was also detected at high levels during larval and adult stages. The expression decreased significantly after pupation. These results provided information concerning molecular structure characteristics of Hh-DH-PBAN, whose expression profile suggested that the Hh-DH-PBAN gene might be correlated with larval development and sex pheromone biosynthesis in females of the H. hippophaecolus. 2013 Wiley Periodicals, Inc

  18. Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors

    Science.gov (United States)

    Reyes, T. M.; Lewis, K.; Perrin, M. H.; Kunitake, K. S.; Vaughan, J.; Arias, C. A.; Hogenesch, J. B.; Gulyas, J.; Rivier, J.; Vale, W. W.; Sawchenko, P. E.

    2001-01-01

    Here we describe the cloning and initial characterization of a previously unidentified CRF-related neuropeptide, urocortin II (Ucn II). Searches of the public human genome database identified a region with significant sequence homology to the CRF neuropeptide family. By using homologous primers deduced from the human sequence, a mouse cDNA was isolated from whole brain poly(A)+ RNA that encodes a predicted 38-aa peptide, structurally related to the other known mammalian family members, CRF and Ucn. Ucn II binds selectively to the type 2 CRF receptor (CRF-R2), with no appreciable activity on CRF-R1. Transcripts encoding Ucn II are expressed in discrete regions of the rodent central nervous system, including stress-related cell groups in the hypothalamus (paraventricular and arcuate nuclei) and brainstem (locus coeruleus). Central administration of 1–10 μg of peptide elicits activational responses (Fos induction) preferentially within a core circuitry subserving autonomic and neuroendocrine regulation, but whose overall pattern does not broadly mimic the CRF-R2 distribution. Behaviorally, central Ucn II attenuates nighttime feeding, with a time course distinct from that seen in response to CRF. In contrast to CRF, however, central Ucn II failed to increase gross motor activity. These findings identify Ucn II as a new member of the CRF family of neuropeptides, which is expressed centrally and binds selectively to CRF-R2. Initial functional studies are consistent with Ucn II involvement in central autonomic and appetitive control, but not in generalized behavioral activation. PMID:11226328

  19. Activity Induces Fmr1-Sensitive Synaptic Capture of Anterograde Circulating Neuropeptide Vesicles.

    Science.gov (United States)

    Cavolo, Samantha L; Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

    2016-11-16

    Synaptic neuropeptide and neurotrophin stores are maintained by constitutive bidirectional capture of dense-core vesicles (DCVs) as they circulate in and out of the nerve terminal. Activity increases DCV capture to rapidly replenish synaptic neuropeptide stores following release. However, it is not known whether this is due to enhanced bidirectional capture. Here experiments at the Drosophila neuromuscular junction, where DCVs contain neuropeptides and a bone morphogenic protein, show that activity-dependent replenishment of synaptic neuropeptides following release is evident after inhibiting the retrograde transport with the dynactin disruptor mycalolide B or photobleaching DCVs entering a synaptic bouton by retrograde transport. In contrast, photobleaching anterograde transport vesicles entering a bouton inhibits neuropeptide replenishment after activity. Furthermore, tracking of individual DCVs moving through boutons shows that activity selectively increases capture of DCVs undergoing anterograde transport. Finally, upregulating fragile X mental retardation 1 protein (Fmr1, also called FMRP) acts independently of futsch/MAP-1B to abolish activity-dependent, but not constitutive, capture. Fmr1 also reduces presynaptic neuropeptide stores without affecting activity-independent delivery and evoked release. Therefore, presynaptic motoneuron neuropeptide storage is increased by a vesicle capture mechanism that is distinguished from constitutive bidirectional capture by activity dependence, anterograde selectivity, and Fmr1 sensitivity. These results show that activity recruits a separate mechanism than used at rest to stimulate additional synaptic capture of DCVs for future release of neuropeptides and neurotrophins. Synaptic release of neuropeptides and neurotrophins depends on presynaptic accumulation of dense-core vesicles (DCVs). At rest, DCVs are captured bidirectionally as they circulate through Drosophila motoneuron terminals by anterograde and retrograde

  20. Amodal processing in human prefrontal cortex.

    Science.gov (United States)

    Tamber-Rosenau, Benjamin J; Dux, Paul E; Tombu, Michael N; Asplund, Christopher L; Marois, René

    2013-07-10

    Information enters the cortex via modality-specific sensory regions, whereas actions are produced by modality-specific motor regions. Intervening central stages of information processing map sensation to behavior. Humans perform this central processing in a flexible, abstract manner such that sensory information in any modality can lead to response via any motor system. Cognitive theories account for such flexible behavior by positing amodal central information processing (e.g., "central executive," Baddeley and Hitch, 1974; "supervisory attentional system," Norman and Shallice, 1986; "response selection bottleneck," Pashler, 1994). However, the extent to which brain regions embodying central mechanisms of information processing are amodal remains unclear. Here we apply multivariate pattern analysis to functional magnetic resonance imaging (fMRI) data to compare response selection, a cognitive process widely believed to recruit an amodal central resource across sensory and motor modalities. We show that most frontal and parietal cortical areas known to activate across a wide variety of tasks code modality, casting doubt on the notion that these regions embody a central processor devoid of modality representation. Importantly, regions of anterior insula and dorsolateral prefrontal cortex consistently failed to code modality across four experiments. However, these areas code at least one other task dimension, process (instantiated as response selection vs response execution), ensuring that failure to find coding of modality is not driven by insensitivity of multivariate pattern analysis in these regions. We conclude that abstract encoding of information modality is primarily a property of subregions of the prefrontal cortex.

  1. Loss of Huntingtin stimulates capture of retrograde dense-core vesicles to increase synaptic neuropeptide stores.

    Science.gov (United States)

    Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

    2017-08-01

    The Huntington's disease protein Huntingtin (Htt) regulates axonal transport of dense-core vesicles (DCVs) containing neurotrophins and neuropeptides. DCVs travel down axons to reach nerve terminals where they are either captured in synaptic boutons to support later release or reverse direction to reenter the axon as part of vesicle circulation. Currently, the impact of Htt on DCV dynamics in the terminal is unknown. Here we report that knockout of Drosophila Htt selectively reduces retrograde DCV flux at proximal boutons of motoneuron terminals. However, initiation of retrograde transport at the most distal bouton and transport velocity are unaffected suggesting that synaptic capture rate of these retrograde DCVs could be altered. In fact, tracking DCVs shows that retrograde synaptic capture efficiency is significantly elevated by Htt knockout or knockdown. Furthermore, synaptic boutons contain more neuropeptide in Htt knockout larvae even though bouton size, single DCV fluorescence intensity, neuropeptide release in response to electrical stimulation and subsequent activity-dependent capture are unaffected. Thus, loss of Htt increases synaptic capture as DCVs travel by retrograde transport through boutons resulting in reduced transport toward the axon and increased neuropeptide in the terminal. These results therefore identify native Htt as a regulator of synaptic capture and neuropeptide storage. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. Primary structure of an adipokinetic neuropeptide from the rhinoceros beetle, Oryctes rhinoceros L (Coleoptera: Dynastidae).

    Science.gov (United States)

    Ajay Kumar, A P; Gokuldas, M

    2011-07-01

    Neuropeptides play an important role in cellular communication in vertebrates. This is also true for insects in which many physiological, developmental and behavioral processes are affected by neuropeptides produced in neurosecretory cells of the retrocerebral complex. Small neuropeptides of the adipokinetic hormone/red pigment concentrating hormone family (AKH/RPCH) are one of the important groups of peptides that regulate physiological homeostasis. The present investigation was carried out to elucidate the primary structure of adipokinetic neuropeptides in the rhinoceros beetle, O. rhinoceros. In the present investigation, an adipokinetic neuropeptide from the coconut pest, Oryctes rhinoceros was isolated from corpora cardiaca by HPLC; the chromatographic fractions were tested for adipokinetic activity in the plant bug, Iphita limbata in vivo. Two UV absorbance peaks were found to be significantly active in elevating haemolymph lipid levels. MALDI-MS analysis of the extract indicated that the molecular mass, 1003.70 Da is similar to the already known AKH from another beetle, Melolontha melolontha. MALDI-MS/MS analysis confirmed that its primary structure is exactly similar to the structure reported for the Melme-AKH (pE-L-N-Y-S-P-D-W-NH2). The findings suggest that the distribution of AKH peptides has shown that there exists a taxonomic order or family specificity. This data can be used as additional information to aid in the construction of phylogenetic trees by means of computer programme and protein parsimony algorithms.

  3. Development of neuropeptide Y-mediated heart innervation in rats.

    Science.gov (United States)

    Masliukov, Petr M; Moiseev, Konstantin; Emanuilov, Andrey I; Anikina, Tatyana A; Zverev, Alexey A; Nozdrachev, Alexandr D

    2016-02-01

    Neuropeptide Y (NPY) plays a trophic role in the nervous and vascular systems and in cardiac hypertrophy. However, there is no report concerning the expression of NPY and its receptors in the heart during postnatal development. In the current study, immunohistochemistry and Western blot analysis was used to label NPY, and Y1R, Y2R, and Y5R receptors in the heart tissue and intramural cardiac ganglia from rats of different ages (newborn, 10 days old, 20 days old, 30 days old, 60 days old, 1 year old, and 2 years old).The obtained data suggest age-dependent changes of NPY-mediated heart innervation. The density of NPY-immunoreactive (IR) fibers was the least in newborn animals and increased in the first 20 days of life. In the atria of newborn and 10-day-old rats, NPY-IR fibers were more abundant compared with the ventricles. The vast majority of NPY-IR fibers also contained tyrosine hydroxylase, a key enzyme in catecholamine synthesis.The expression of Y1R increased between 10 and 20 days of life. Faint Y2R immunoreactivity was observed in the atria and ventricles of 20-day-old and older rats. In contrast, the highest level of the expression of Y5R was found in newborn pups comparing with more adult rats. All intramural ganglionic neurons were also Y1R-IR and Y5R-IR and Y2R-negative in all studied animals.Thus, the increasing of density of NPY-containing nerve fibers accompanies changes in relation of different subtypes of NPY receptors in the heart during development.

  4. The Neuropeptide Oxytocin Induces a Social Altruism Bias.

    Science.gov (United States)

    Marsh, Nina; Scheele, Dirk; Gerhardt, Holger; Strang, Sabrina; Enax, Laura; Weber, Bernd; Maier, Wolfgang; Hurlemann, René

    2015-11-25

    Current psychological concepts of social and ecological responsibility emphasize the relevance of altruism, suggesting that more altruistic individuals are more likely to engage in sustainable behaviors. Emerging evidence indicates a central role of the neuropeptide oxytocin in promoting altruism. Whether this influence extends to ecological responsibility or is limited to the social domain remains unknown. In two independent experiments involving 172 human participants, we addressed this question by exposing subjects to a sustainability-related monetary donation task, with the option to support either socially or ecologically framed charities. We found that oxytocin induced a context-dependent change in altruistic behavior away from pro-environmental toward pro-social donations, while keeping constant the overall proportion of donated money. This pro-social bias transcended to the domain of sustainable consumption. Collectively, our findings demonstrate that altruistic priorities vary as a function of oxytocin system activity, which has implications for the promotion of pro-environmental attitudes and eco-friendly behaviors. Individual responses to ecological and social sustainability require a shift in personal priorities away from selfish to more altruistic behaviors. Emerging evidence indicates a central role of the hypothalamic peptide oxytocin in promoting altruism, but whether the influence of oxytocin benefits altruistic decision-making in the context of ecological and social sustainability is unclear. In two independent behavioral experiments involving 172 human subjects, we show that heightened oxytocin system activity induces a social altruism bias at the cost of ecological responsibility. Our results have fundamental implications for policy interventions and business strategies designed to sustain ecological resources by suggesting that a social framing may attract more individuals to engage in pro-environmental and eco-friendly behaviors. Copyright

  5. Role of sympathetic nervous system and neuropeptides in obesity hypertension

    Directory of Open Access Journals (Sweden)

    J.E. Hall

    2000-06-01

    Full Text Available Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium retention and hypertension since adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the hypothalamus may link excess weight gain with increased sympathetic activity. Leptin is produced mainly in adipocytes and is believed to regulate energy balance by acting on the hypothalamus to reduce food intake and to increase energy expenditure via sympathetic activation. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term leptin infusion at rates that mimic plasma concentrations found in obesity raises arterial pressure and heart rate via adrenergic activation in non-obese rodents. Transgenic mice overexpressing leptin also develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including the melanocortin-4 receptor (MC4-R. However, the role of this pathway in mediating the long-term effects of leptin on blood pressure is unclear. Also, it is uncertain whether there is resistance to the chronic renal sympathetic and blood pressure effects of leptin in obese subjects. In addition, leptin also has other cardiovascular and renal actions, such as stimulation of nitric oxide formation and improvement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the role of these mechanisms in human obesity has not been elucidated, this

  6. Effects of a skin neuropeptide (substance p on cutaneous microflora.

    Directory of Open Access Journals (Sweden)

    Lily Mijouin

    Full Text Available BACKGROUND: Skin is the largest human neuroendocrine organ and hosts the second most numerous microbial population but the interaction of skin neuropeptides with the microflora has never been investigated. We studied the effect of Substance P (SP, a peptide released by nerve endings in the skin on bacterial virulence. METHODOLOGY/PRINCIPAL FINDINGS: Bacillus cereus, a member of the skin transient microflora, was used as a model. Exposure to SP strongly stimulated the cytotoxicity of B. cereus (+553±3% with SP 10(-6 M and this effect was rapid (<5 min. Infection of keratinocytes with SP treated B. cereus led to a rise in caspase1 and morphological alterations of the actin cytoskeleton. Secretome analysis revealed that SP stimulated the release of collagenase and superoxide dismutase. Moreover, we also noted a shift in the surface polarity of the bacteria linked to a peel-off of the S-layer and the release of S-layer proteins. Meanwhile, the biofilm formation activity of B. cereus was increased. The Thermo unstable ribosomal Elongation factor (Ef-Tu was identified as the SP binding site in B. cereus. Other Gram positive skin bacteria, namely Staphylococcus aureus and Staphylococcus epidermidis also reacted to SP by an increase of virulence. Thermal water from Uriage-les-Bains and an artificial polysaccharide (Teflose® were capable to antagonize the effect of SP on bacterial virulence. CONCLUSIONS/SIGNIFICANCE: SP is released in sweat during stress and is known to be involved in the pathogenesis of numerous skin diseases through neurogenic inflammation. Our study suggests that a direct effect of SP on the skin microbiote should be another mechanism.

  7. Effects of ghrelin on circulating neuropeptide Y levels in humans.

    Science.gov (United States)

    Coiro, Vittorio; Saccani-Jotti, Gloria; Rubino, Pasquale; Manfredi, Guido; Melani, Andrea; Chiodera, Paolo

    2006-12-01

    Ghrelin is a 28 amino-acid peptide with a strong GH-releasing activity and a complex role in regulation of appetite, fuel utilization, body weight and composition. Neuropeptide Y (NPY) is a well-known stimulator of pathways favouring food intake and energy storage. Recently, studies in rodents suggested a possible mediation of ghrelin action by NPY. In contrast, until now no evidence of ghrelin-NPY interaction in humans has been provided. In the present study, we examined whether ghrelin influences NPY secretion in normal men. Twelve healthy normal men (aged 24-35 years; body mass index (BMI) 22.3+/-0.93 kg/m2) were tested twice at 08.00 AM on two different days, in random order at weekly intervals, after an overnight fast and rest in bed. An intravenous bolus of 1 microg/kg body weight ghrelin (esperimental test) or an equal amount of normal saline (control test) was injected at time 0. Blood was taken before and over 90 minutes after injections, and was used for the measurement of plasma NPY levels. Plasma levels of NPY slightly, but significantly rose in response to ghrelin, with a mean peak level at 15 min after injection, whereas no significant change was observed after saline administration. Our results show a significant enhancement of plasma NPY levels under ghrelin stimulation. To our knowledge, this is the first demonstration of a ghrelin-NPY interaction in humans, which may suggest a possible mediation of ghrelin action by NPY in humans.

  8. The anterior cingulate cortex

    Directory of Open Access Journals (Sweden)

    Pavlović D.M.

    2009-01-01

    Full Text Available The anterior cingulate cortex (ACC has a role in attention, analysis of sensory information, error recognition, problem solving, detection of novelty, behavior, emotions, social relations, cognitive control, and regulation of visceral functions. This area is active whenever the individual feels some emotions, solves a problem, or analyzes the pros and cons of an action (if it is a right decision. Analogous areas are also found in higher mammals, especially whales, and they contain spindle neurons that enable complex social interactions. Disturbance of ACC activity is found in dementias, schizophrenia, depression, the obsessive-compulsive syndrome, and other neuropsychiatric diseases.

  9. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

    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...... 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...... of a regulatory effect of the PFC on the emotional control of our actions....

  10. Neural mechanisms of memory retrieval: role of the prefrontal cortex.

    Science.gov (United States)

    Hasegawa, I

    2000-01-01

    In the primate brain, long-term memory is stored in the neocortical association area which is also engaged in sensory perception. The coded representation of memory is retrieved via interactions of hierarchically different cortical areas along bottom-up and top-down anatomical connections. The functional significance of the fronto-cortical top-down neuronal projections has been relevantly assessed in a new experimental paradigm using posterior-split-brain monkeys. When the splenium of the corpus callosum and the anterior commissure were selectively split, the bottom-up visual signal originating from the unilateral striate cortex could not reach the contralateral visual cortical areas. In this preparation, long-term memory acquired through visual stimulus-stimulus association learning was prevented from transferring across hemispheres. Nonetheless, following the presentation of a visual cue to one hemisphere, the prefrontal cortex could instruct the contralateral hemisphere to retrieve the correct stimulus specified by the cue. These results support the hypothesis that the prefrontal cortex can regulate memory recall in the absence of bottom-up sensory input. In humans, functional neuroimaging studies have revealed activation of a distributed neural network, including the prefrontal cortex, during memory retrieval tasks. Thus, the prefrontal cortex is consistently involved in retrieval of long-term memory in primates.

  11. [Brodmann Areas 20, 21, and 22 in the Cerebral Cortex].

    Science.gov (United States)

    Kaga, Kimitaka; Minami, Shujiro B

    2017-04-01

    The 20, 21, and 22 areas in the temporal lobe as classified by Brodmann are almost identical with Economo and Koskinas's TA, TE1, and TE2, and, generally, with the gyrus, middle temporal gyrus, and inferior temporal gyrus according to brain anatomy. Before Brodmann's classification, Flechsig published his book "Soul and Brain" in 1897, in which primary, secondary, and association areas in the brain were classified. More recently, results from research using magnetic resonance imaging (MRI) and fMRI support the parcellation of the cerebral cortex proposed by Flechsig, Brodmann, and Economo more than one century ago.

  12. MRI of the brain: malformations

    International Nuclear Information System (INIS)

    Treguier, C.; Heautot, J.F.; Gandon, Y.; Carsin, M.; Buhe, T.; Weppe, V.

    1990-01-01

    Brain malformations include occlusion, diverticula, neuronal migration abnormalities, cystic malformations, and histogenetic disorders in neurocutaneous syndromes. The multiple planes of section, excellent white/gray matter differentiation and accurate delineation of the brain cortex available with magnetic resonance imaging make it a tool of choice for the diagnosis of malformations, as well as for prognosis and genetic counseling [fr

  13. The primary motor and premotor areas of the human cerebral cortex.

    Science.gov (United States)

    Chouinard, Philippe A; Paus, Tomás

    2006-04-01

    Brodmann's cytoarchitectonic map of the human cortex designates area 4 as cortex in the anterior bank of the precentral sulcus and area 6 as cortex encompassing the precentral gyrus and the posterior portion of the superior frontal gyrus on both the lateral and medial surfaces of the brain. More than 70 years ago, Fulton proposed a functional distinction between these two areas, coining the terms primary motor area for cortex in Brodmann area 4 and premotor area for cortex in Brodmann area 6. The parcellation of the cortical motor system has subsequently become more complex. Several nonprimary motor areas have been identified in the brain of the macaque monkey, and associations between anatomy and function in the human brain are being tested continuously using brain mapping techniques. In the present review, the authors discuss the unique properties of the primary motor area (M1), the dorsal portion of the premotor cortex (PMd), and the ventral portion of the premotor cortex (PMv). They end this review by discussing how the premotor areas influence M1.

  14. Rat Brain Biogenic Amine Levels during Acute and Sub- acute ...

    African Journals Online (AJOL)

    User

    2011-05-20

    May 20, 2011 ... substances in rat brain regions are altered during acute and sub-acute .... Different areas of the brain such as cerebral cortex (CC), cerebellum (CB), .... dopamine metabolism and differential motor behavioral tolerance.

  15. Auditory and visual connectivity gradients in frontoparietal cortex.

    Science.gov (United States)

    Braga, Rodrigo M; Hellyer, Peter J; Wise, Richard J S; Leech, Robert

    2017-01-01

    A frontoparietal network of brain regions is often implicated in both auditory and visual information processing. Although it is possible that the same set of multimodal regions subserves both modalities, there is increasing evidence that there is a differentiation of sensory function within frontoparietal cortex. Magnetic resonance imaging (MRI) in humans was used to investigate whether different frontoparietal regions showed intrinsic biases in connectivity with visual or auditory modalities. Structural connectivity was assessed with diffusion tractography and functional connectivity was tested using functional MRI. A dorsal-ventral gradient of function was observed, where connectivity with visual cortex dominates dorsal frontal and parietal connections, while connectivity with auditory cortex dominates ventral frontal and parietal regions. A gradient was also observed along the posterior-anterior axis, although in opposite directions in prefrontal and parietal cortices. The results suggest that the location of neural activity within frontoparietal cortex may be influenced by these intrinsic biases toward visual and auditory processing. Thus, the location of activity in frontoparietal cortex may be influenced as much by stimulus modality as the cognitive demands of a task. It was concluded that stimulus modality was spatially encoded throughout frontal and parietal cortices, and was speculated that such an arrangement allows for top-down modulation of modality-specific information to occur within higher-order cortex. This could provide a potentially faster and more efficient pathway by which top-down selection between sensory modalities could occur, by constraining modulations to within frontal and parietal regions, rather than long-range connections to sensory cortices. Hum Brain Mapp 38:255-270, 2017. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  16. Effect of incubation temperature on neuropeptide Y and neuropeptide Y receptors in turkey and chicken satellite cells.

    Science.gov (United States)

    Clark, Daniel L; McCormick, Janet L; Velleman, Sandra G

    2018-05-01

    Neuropeptide Y (NPY) is an appetite stimulating peptide released from the central nervous system and impacts the function of many different cell types. A recent transcriptome study showed that NPY expression was altered when turkey breast muscle satellite cells were incubated at low or high temperatures, suggesting NPY may mediate temperature effects on satellite cells. However, to date minimal information exists describing the expression and function of NPY in satellite cells. The objective of this study was to determine how temperature impacts NPY and NPY receptor gene expression in satellite cells isolated from turkeys and chickens with differing genetic lineages. Two broiler and two turkey breast muscle satellite cell lines were incubated at 35, 38 or 41 °C during proliferation and differentiation. In both turkey lines, NPY, and receptors NPY2R and NPY5R expression increased at elevated temperatures after 72 h of proliferation. During differentiation NPY and NPY5R expression increased in both turkey lines with higher temperatures, whereas NPY2R was minimally affected by temperature. In contrast, in both chicken cell lines there were few significant differences for NPY and NPY receptor expression across temperature during proliferation. During differentiation, the temperature effect was different in the two chicken cell lines. In the BPM8 chicken line, there were few differences in NPY and NPY receptors across temperature; whereas elevated temperatures increased NPY, NPY2R, and NPY5R expression in the 708 line. The differences between turkey and chicken lines suggest NPY has species specific satellite cell functions in response to heat stress. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. The Role of the Insular Cortex in Retaliation.

    Directory of Open Access Journals (Sweden)

    Franziska Emmerling

    Full Text Available The insular cortex has consistently been associated with various aspects of emotion regulation and social interaction, including anger processing and overt aggression. Aggression research distinguishes proactive or instrumental aggression from retaliation, i.e. aggression in response to provocation. Here, we investigated the specific role of the insular cortex during retaliation, employing a controlled behavioral aggression paradigm implementing different levels of provocation. Fifteen healthy male volunteers underwent whole brain functional magnetic resonance imaging (fMRI to identify brain regions involved in interaction with either a provoking or a non-provoking opponent. FMRI group analyses were complemented by examining the parametric modulations of brain activity related to the individual level of displayed aggression. These analyses identified a hemispheric lateralization as well as an anatomical segregation of insular cortex with specifically the left posterior part being involved in retaliation. The left-lateralization of insular activity during retaliation is in accordance with evidence from electro-physiological studies, suggesting left-lateralized fronto-cortical dominance during anger processing and aggressive acts. The posterior localization of insular activity, on the other hand, suggests a spatial segregation within insular cortex with particularly the posterior part being involved in the processing of emotions that trigger intense bodily sensations and immediate action tendencies.

  18. Adeno-Associated Viral Vector-Induced Overexpression of Neuropeptide Y Y2 Receptors in the Hippocampus Suppresses Seizures

    Science.gov (United States)

    Woldbye, David P. D.; Angehagen, Mikael; Gotzsche, Casper R.; Elbrond-Bek, Heidi; Sorensen, Andreas T.; Christiansen, Soren H.; Olesen, Mikkel V.; Nikitidou, Litsa; Hansen, Thomas v. O.; Kanter-Schlifke, Irene; Kokaia, Merab

    2010-01-01

    Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure suppression by neuropeptide Y in the hippocampus is…

  19. Phosphopeptidomics Reveals Differential Phosphorylation States and Novel SxE Phosphosite Motifs of Neuropeptides in Dense Core Secretory Vesicles

    Science.gov (United States)

    Lietz, Christopher B.; Toneff, Thomas; Mosier, Charles; Podvin, Sonia; O'Donoghue, Anthony J.; Hook, Vivian

    2018-03-01

    Neuropeptides are vital for cell-cell communication and function in the regulation of the nervous and endocrine systems. They are generated by post-translational modification (PTM) steps resulting in small active peptides generated from prohormone precursors. Phosphorylation is a significant PTM for the bioactivity of neuropeptides. From the known diversity of distinct neuropeptide functions, it is hypothesized that the extent of phosphorylation varies among different neuropeptides. To assess this hypothesis, neuropeptide-containing dense core secretory vesicles from bovine adrenal medullary chromaffin cells were subjected to global phosphopeptidomics analyses by liquid chromatography (LC)-mass spectrometry (MS/MS). Phosphopeptides were identified directly by LC-MS/MS and indirectly by phosphatase treatment followed by LC-MS/MS. The data identified numerous phosphorylated peptides derived from neuropeptide precursors such as chromogranins, secretogranins, proenkephalin and pro-NPY. Phosphosite occupancies were observed at high and low levels among identified peptides and many of the high occupancy phosphopeptides represent prohormone-derived peptides with currently unknown bioactivities. Peptide sequence analyses demonstrated SxE as the most prevalent phosphorylation site motif, corresponding to phosphorylation sites of the Fam20C protein kinase known to be present in the secretory pathway. The range of high to low phosphosite occupancies for neuropeptides demonstrates cellular regulation of neuropeptide phosphorylation. [Figure not available: see fulltext.

  20. Isolation of L-3-phenyllactyl-Phe-Lys-Ala-NH2 (Antho-KAamide), a novel neuropeptide from sea anemones

    DEFF Research Database (Denmark)

    Nothacker, H P; Rinehart, K L; Grimmelikhuijzen, C J

    1991-01-01

    sea anemones. We propose that the L-3-phenyllactyl residue renders Antho-KAamide resistant to nonspecific aminopeptidases, thereby increasing the stability of the neuropeptide after neuronal release. The existence of the L-3-phenyllactyl residue in 3 neuropeptides isolated so far suggests...

  1. Phosphopeptidomics Reveals Differential Phosphorylation States and Novel SxE Phosphosite Motifs of Neuropeptides in Dense Core Secretory Vesicles

    Science.gov (United States)

    Lietz, Christopher B.; Toneff, Thomas; Mosier, Charles; Podvin, Sonia; O'Donoghue, Anthony J.; Hook, Vivian

    2018-05-01

    Neuropeptides are vital for cell-cell communication and function in the regulation of the nervous and endocrine systems. They are generated by post-translational modification (PTM) steps resulting in small active peptides generated from prohormone precursors. Phosphorylation is a significant PTM for the bioactivity of neuropeptides. From the known diversity of distinct neuropeptide functions, it is hypothesized that the extent of phosphorylation varies among different neuropeptides. To assess this hypothesis, neuropeptide-containing dense core secretory vesicles from bovine adrenal medullary chromaffin cells were subjected to global phosphopeptidomics analyses by liquid chromatography (LC)-mass spectrometry (MS/MS). Phosphopeptides were identified directly by LC-MS/MS and indirectly by phosphatase treatment followed by LC-MS/MS. The data identified numerous phosphorylated peptides derived from neuropeptide precursors such as chromogranins, secretogranins, proenkephalin and pro-NPY. Phosphosite occupancies were observed at high and low levels among identified peptides and many of the high occupancy phosphopeptides represent prohormone-derived peptides with currently unknown bioactivities. Peptide sequence analyses demonstrated SxE as the most prevalent phosphorylation site motif, corresponding to phosphorylation sites of the Fam20C protein kinase known to be present in the secretory pathway. The range of high to low phosphosite occupancies for neuropeptides demonstrates cellular regulation of neuropeptide phosphorylation. [Figure not available: see fulltext.

  2. Prevention of stress-impaired fear extinction through neuropeptide s action in the lateral amygdala.

    Science.gov (United States)

    Chauveau, Frédéric; Lange, Maren Denise; Jüngling, Kay; Lesting, Jörg; Seidenbecher, Thomas; Pape, Hans-Christian

    2012-06-01

    Stressful and traumatic events can create aversive memories, which are a predisposing factor for anxiety disorders. The amygdala is critical for transforming such stressful events into anxiety, and the recently discovered neuropeptide S transmitter system represents a promising candidate apt to control these interactions. Here we test the hypothesis that neuropeptide S can regulate stress-induced hyperexcitability in the amygdala, and thereby can interact with stress-induced alterations of fear memory. Mice underwent acute immobilization stress (IS), and neuropeptide S and a receptor antagonist were locally injected into the lateral amygdala (LA) during stress exposure. Ten days later, anxiety-like behavior, fear acquisition, fear memory retrieval, and extinction were tested. Furthermore, patch-clamp recordings were performed in amygdala slices prepared ex vivo to identify synaptic substrates of stress-induced alterations in fear responsiveness. (1) IS increased anxiety-like behavior, and enhanced conditioned fear responses during extinction 10 days after stress, (2) neuropeptide S in the amygdala prevented, while an antagonist aggravated, these stress-induced changes of aversive behaviors, (3) excitatory synaptic activity in LA projection neurons was increased on fear conditioning and returned to pre-conditioning values on fear extinction, and (4) stress resulted in sustained high levels of excitatory synaptic activity during fear extinction, whereas neuropeptide S supported the return of synaptic activity during fear extinction to levels typical of non-stressed animals. Together these results suggest that the neuropeptide S system is capable of interfering with mechanisms in the amygdala that transform stressful events into anxiety and impaired fear extinction.

  3. Settlement induction of Acropora palmata planulae by a GLW-amide neuropeptide

    Science.gov (United States)

    Erwin, P. M.; Szmant, A. M.

    2010-12-01

    Complex environmental cues dictate the settlement of coral planulae in situ; however, simple artificial cues may be all that is required to induce settlement of ex situ larval cultures for reef re-seeding and restoration projects. Neuropeptides that transmit settlement signals and initiate the metamorphic cascade have been isolated from hydrozoan taxa and shown to induce metamorphosis of reef-building Acropora spp. in the Indo-Pacific, providing a reliable and efficient settlement cue. Here, the metamorphic activity of six GLW-amide cnidarian neuropeptides was tested on larvae of the Caribbean corals Acropora palmata, Montastraea faveolata and Favia fragum. A. palmata planulae were induced to settle by the exogenous application of the neuropeptide Hym-248 (concentrations ≥1 × 10-6 M), achieving 40-80% attachment and 100% metamorphosis of competent planulae (≥6 days post-fertilization) during two spawning seasons; the remaining neuropeptides exhibited no activity. Hym-248 exposure rapidly altered larval swimming behavior (96% metamorphosis after 6 h. In contrast , M. faveolata and F. fragum planulae did not respond to any GLW-amides tested, suggesting a high specificity of neuropeptide activators on lower taxonomic scales in corals. Subsequent experiments for A. palmata revealed that (1) the presence of a biofilm did not enhance attachment efficiency when coupled with Hym-248 treatment, (2) neuropeptide-induced settlement had no negative effects on early life-history developmental processes: zooxanthellae acquisition and skeletal secretion occurred within 12 days, colonial growth occurred within 36 days, and (3) Hym-248 solutions maintained metamorphic activity following storage at room temperature (10 days), indicating its utility in remote field settings. These results corroborate previous studies on Indo-Pacific Acropora spp. and extend the known metamorphic activity of Hym-248 to Caribbean acroporids. Hym-248 allows for directed and reliable settlement of

  4. Expression Profiles of Neuropeptides, Neurotransmitters, and Their Receptors in Human Keratocytes In Vitro and In Situ.

    Science.gov (United States)

    Słoniecka, Marta; Le Roux, Sandrine; Boman, Peter; Byström, Berit; Zhou, Qingjun; Danielson, Patrik

    2015-01-01

    Keratocytes, the quiescent cells of the corneal stroma, play a crucial role in corneal wound healing. Neuropeptides and neurotransmitters are usually associated with neuronal signaling, but have recently been shown to be produced also by non-neuronal cells and to be involved in many cellular processes. The aim of this study was to assess the endogenous intracellular and secreted levels of the neuropeptides substance P (SP) and neurokinin A (NKA), and of the neurotransmitters acetylcholine (ACh), catecholamines (adrenaline, noradrenaline and dopamine), and glutamate, as well as the expression profiles of their receptors, in human primary keratocytes in vitro and in keratocytes of human corneal tissue sections in situ. Cultured keratocytes expressed genes encoding for SP and NKA, and for catecholamine and glutamate synthesizing enzymes, as well as genes for neuropeptide, adrenergic and ACh (muscarinic) receptors. Keratocytes in culture produced SP, NKA, catecholamines, ACh, and glutamate, and expressed neurokinin-1 and -2 receptors (NK-1R and NK-2R), dopamine receptor D2, muscarinic ACh receptors, and NDMAR1 glutamate receptor. Human corneal sections expressed SP, NKA, NK-1R, NK-2R, receptor D2, choline acetyl transferase (ChAT), M3, M4 and M5 muscarinic ACh receptors, glutamate, and NMDAR1, but not catecholamine synthesizing enzyme or the α1 and β2 adrenoreceptors, nor M1 receptor. In addition, expression profiles assumed significant differences between keratocytes from the peripheral cornea as compared to those from the central cornea, as well as differences between keratocytes cultured under various serum concentrations. In conclusion, human keratocytes express an array of neuropeptides and neurotransmitters. The cells furthermore express receptors for neuropeptides/neurotransmitters, which suggests that they are susceptible to stimulation by these substances in the cornea, whether of neuronal or non-neuronal origin. As it has been shown that neuropeptides

  5. Expression of Neuropeptides and Cytokines in a Rabbit Model of Diabetic Neuroischemic Wound-Healing

    Science.gov (United States)

    Nabzdyk, Leena Pradhan; Kuchibhotla, Sarada; Guthrie, Patrick; Chun, Maggie; Auster, Michael E; Nabzdyk, Christoph; Deso, Steven; Andersen, Nicholas; LoGerfo, Frank W.; Veves, Aristidis

    2013-01-01

    Objective The present study is designed to understand the contribution of peripheral vascular disease and peripheral neuropathy to the wound-healing impairment associated with diabetes. Using a rabbit model of diabetic neuroischemic wound-healing we investigated rate of healing, leukocyte infiltration and expression of cytokines, Interleukin (IL)-8 and IL-6, and, neuropeptides, Substance P (SP) and Neuropeptide Y (NPY). Design of study Diabetes was induced in White New Zealand rabbits by administering alloxan while control rabbits received saline. Ten days later animals in both groups underwent surgery. One ear served as a sham and the other was made ischemic (ligation of central+rostral arteries), or neuroischemic (ischemia+ resection of central+rostral nerves). Four, 6mm punch biopsy wounds were created in both ears and wound-healing was followed for ten days using computerized planimetry. Results Non-diabetic sham and ischemic wounds healed significantly more rapidly than diabetic sham and ischemic wounds. Healing was slowest in neuroischemic wounds, irrespective of diabetic status. A high M1/M2 macrophage ratio and a high pro-inflammatory cytokine expression, both indicators of chronic-proinflammatory state, and low neuropeptide expression were seen in pre-injury diabetic skin. Post-injury, in diabetic wounds M1/M2 ratio remained high, the reactive increase in cytokine expression was low and neuropeptide expression was further decreased in neuroischemic wounds. Conclusion This rabbit model illustrates how a combination of a high M1/M2 ratio, a failure to mount post-injury cytokine response as well as a diminished neuropeptide expression contribute to wound-healing impairment in diabetes. The addition of neuropathy to ischemia leads to equivalently severe impaired wound-healing irrespective of diabetes status, suggesting that in the presence of ischemia, loss of neuropeptide function contributes to the impaired healing associated with diabetes. PMID:23755976

  6. Anorexia in human and experimental animal models: physiological aspects related to neuropeptides.

    Science.gov (United States)

    Yoshimura, Mitsuhiro; Uezono, Yasuhito; Ueta, Yoichi

    2015-09-01

    Anorexia, a loss of appetite for food, can be caused by various physiological and pathophysiological conditions. In this review, firstly, clinical aspects of anorexia nervosa are summarized in brief. Secondly, hypothalamic neuropeptides responsible for feeding regulation in each hypothalamic nucleus are discussed. Finally, three different types of anorexigenic animal models; dehydration-induced anorexia, cisplatin-induced anorexia and cancer anorexia-cachexia, are introduced. In conclusion, hypothalamic neuropeptides may give us novel insight to understand and find effective therapeutics strategy essential for various kinds of anorexia.

  7. Identifying neuropeptide and protein hormone receptors in Drosophila melanogaster by exploiting genomic data

    DEFF Research Database (Denmark)

    Hauser, Frank; Williamson, Michael; Cazzamali, Giuseppe

    2006-01-01

    insect genome, that of the fruitfly Drosophila melanogaster, was sequenced in 2000, and about 200 GPCRs have been annnotated in this model insect. About 50 of these receptors were predicted to have neuropeptides or protein hormones as their ligands. Since 2000, the cDNAs of most of these candidate...... receptors have been cloned and for many receptors the endogenous ligand has been identified. In this review, we will give an update about the current knowledge of all Drosophila neuropeptide and protein hormone receptors, and discuss their phylogenetic relationships. Udgivelsesdato: 2006-Feb...

  8. Word Recognition in Auditory Cortex

    Science.gov (United States)

    DeWitt, Iain D. J.

    2013-01-01

    Although spoken word recognition is more fundamental to human communication than text recognition, knowledge of word-processing in auditory cortex is comparatively impoverished. This dissertation synthesizes current models of auditory cortex, models of cortical pattern recognition, models of single-word reading, results in phonetics and results in…

  9. Effect of skull type on the relative size of cerebral cortex and lateral ventricles in dogs

    DEFF Research Database (Denmark)

    Pilegaard, Anders M.; Berendt, Mette; Holst, Pernille

    2017-01-01

    Volume measurements of the brain are of interest in the diagnosis of brain pathology. This is particularly so in the investigation hydrocephalus and canine cognitive dysfunction (CCD), both of which result in thinning of the cerebral cortex and enlarged ventricles. Volume assessment can be made...

  10. Understanding the Dorsal and Ventral Systems of the Human Cerebral Cortex: Beyond Dichotomies

    Science.gov (United States)

    Borst, Gregoire; Thompson, William L.; Kosslyn, Stephen M.

    2011-01-01

    Traditionally, characterizations of the macrolevel functional organization of the human cerebral cortex have focused on the left and right cerebral hemispheres. However, the idea of left brain versus right brain functions has been shown to be an oversimplification. We argue here that a top-bottom divide, rather than a left-right divide, is a more…

  11. Glucagon-like peptide-1 (GLP-1) raises blood-brain glucose transfer capacity and hexokinase activity in human brain

    DEFF Research Database (Denmark)

    Gejl, Michael; Lerche, Susanne; Egefjord, Lærke

    2013-01-01

    phosphorylation velocity (V max) in the gray matter regions of cerebral cortex, thalamus, and cerebellum, as well as increased blood-brain glucose transport capacity (T max) in gray matter, white matter, cortex, thalamus, and cerebellum. In hypoglycemia, GLP-1 had no effects on net glucose metabolism, brain...

  12. Interplay of hippocampus and prefrontal cortex in memory

    Science.gov (United States)

    Preston, Alison R.; Eichenbaum, Howard

    2013-01-01

    Recent studies on the hippocampus and the prefrontal cortex have considerably advanced our understanding of the distinct roles of these brain areas in the encoding and retrieval of memories, and of how they interact in the prolonged process by which new memories are consolidated into our permanent storehouse of knowledge. These studies have led to a new model of how the hippocampus forms and replays memories and how the prefrontal cortex engages representations of the meaningful contexts in which related memories occur, as well as how these areas interact during memory retrieval. Furthermore, they have provided new insights into how interactions between the hippocampus and prefrontal cortex support the assimilation of new memories into pre-existing networks of knowledge, called schemas, and how schemas are modified in this process as the foundation of memory consolidation. PMID:24028960

  13. Initial brain aging

    DEFF Research Database (Denmark)

    Thomsen, Kirsten; Yokota, Takashi; Hasan-Olive, Md Mahdi

    2018-01-01

    Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB(m/m)) and C57Bl/6 (WT......) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB(m/m) hippocampus, but not in CSB(m/m) cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased....... Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSB(m/m) compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event...

  14. Receptor subtypes Y1 and Y5 are involved in the renal effects of neuropeptide Y

    NARCIS (Netherlands)

    Bischoff, A.; Avramidis, P.; Erdbrügger, W.; Münter, K.; Michel, M. C.

    1997-01-01

    1. Systemic infusion of neuropeptide Y (NPY) reduces renal blood flow and can concomitantly increase diuresis, natriuresis and calciuresis in anaesthetized rats. The present study was designed to investigate whether the apparently contradictory NPY effects on renal blood flow and urine formation and

  15. Anorexigenní neuropeptid CART v regulaci příjmu potravy

    Czech Academy of Sciences Publication Activity Database

    Nagelová, Veronika; Železná, Blanka; Maletínská, Lenka

    2014-01-01

    Roč. 108, č. 4 (2014), s. 354-357 ISSN 0009-2770 R&D Projects: GA ČR GAP303/10/1368 Institutional support: RVO:61388963 Keywords : CART * cocaine and amphetamine regulated transcript * anorexigenic neuropeptide Subject RIV: CE - Biochemistry Impact factor: 0.272, year: 2014

  16. Study of plasma neuropeptide levels in patients with acute cardiovascular and cerebrovascular disease

    International Nuclear Information System (INIS)

    Xu Youfen; Lan Suixin; Chen Yu; He Ling; Huang Yuan; Ma Yaling

    2003-01-01

    Objective: To explore the relationship between the dynamic changes of plasma neuropeptide (β-EP, NT, NPY) levels and the pathogenesis as well as clinical outcomes of acute cardiovascular and cerebrovascular diseases. Methods: The concentrations of serum neuropeptides (β-EP, NT, NPY) were measured on the 1 st, 3 rd, 7 th, 14 th day after the onset of disease with RIA in 103 patients with acute cardiovascular and cerebrovascular diseases (38 cases of acute cerebral infarction, 32 cases of cerebral hemorrhage, 33 cases of acute myocardial infarction and acute heart failure) and 66 controls. Results: 1. NPY, NT and β-EP levels in patients with acute cardiovascular and cerebrovascular disease were significantly higher than those in controls (p<0.01). (F=39.54, p<0.01; F=33.38, p<0.01; F=8.38, p<0.01 For β-EP, NPY and NT respectively). 2. The plasma neuropeptide levels were highest at onset and gradually lowered till to normal levels on the 14 th day. Conclusion: Plasma neuropeptide levels were closely related to the pathogenesis and clinical outcome of acute cardiovascular and cerebrovascular diseases, study of which might be useful in the clinical management of the diseases

  17. Differential suppression of seizures via Y2 and Y5 neuropeptide Y receptors

    DEFF Research Database (Denmark)

    Woldbye, David P D; Nanobashvili, Avtandil; Sørensen, Andreas Vehus

    2005-01-01

    Neuropeptide Y (NPY) prominently inhibits epileptic seizures in different animal models. The NPY receptors mediating this effect remain controversial partially due to lack of highly selective agonists and antagonists. To circumvent this problem, we used various NPY receptor knockout mice with the...

  18. Vulnerability to psychogenic non-epileptic seizures is linked to low neuropeptide Y levels

    DEFF Research Database (Denmark)

    Winterdahl, Michael; Miani, Alessandro; Vercoe, Moana

    2017-01-01

    Psychogenic non-epileptic seizures (PNES) is a conversion disorder that reflects underlying psychological distress. Female patients with PNES often present with a history of prolonged stressors, especially sexual abuse. In the current study, we studied the relationship between neuropeptide Y (NPY...

  19. [Hormones and osteoporosis update. Regulation of bone remodeling by neuropeptides and neurotransmitters].

    Science.gov (United States)

    Takeda, Shu

    2009-07-01

    From the discovery of the regulation of bone remodelling by leptin, much attention has been focused on neurogenic control of bone remodelling. Various hypothalamic neuropeptides, which are involved in appetite regulation, are now revealed to be important regulators of bone remodelling. More recently, neurotransmitters, such as serotonin or catecholamines, are proven to be bone remodelling regulators.

  20. Molecular cloning and functional expression of a Drosophila receptor for the neuropeptides capa-1 and -2

    DEFF Research Database (Denmark)

    Iversen, Annette; Cazzamali, Giuseppe; Williamson, Michael

    2002-01-01

    the malaria mosquito Anopheles gambiae (58% amino acid residue identities; 76% conserved residues; and 5 introns at identical positions within the two insect genes). Because capa-1 and -2 and related insect neuropeptides stimulate fluid secretion in insect Malpighian (renal) tubules, the identification...

  1. Localisation of the neuropeptide PACAP and its receptors in the rat parathyroid and thyroid glands

    DEFF Research Database (Denmark)

    Fahrenkrug, Jan; Hannibal, Jens

    2011-01-01

    PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2). Here we examined the localisation and nature of PACAP-immunoreactive nerves in the rat thyroid and parathyroid glands and defined the ...

  2. A phosphoproteomics approach to elucidate neuropeptide signal transduction controlling insect metamorphosis

    DEFF Research Database (Denmark)

    Rewitz, Kim F; Larsen, Martin R; Lobner-Olesen, Anders

    2009-01-01

    In insects, the neuropeptide prothoracicotropic hormone (PTTH) stimulates production of ecdysone (E) in the prothoracic glands (PGs). E is the precursor of the principal steroid hormone, 20-hydroxyecdysone (20E), that is responsible for eliciting molting and metamorphosis. In this study, we used...

  3. Early vertebrate chromosome duplications and the evolution of the neuropeptide Y receptor gene regions

    Directory of Open Access Journals (Sweden)

    Brenner Sydney

    2008-06-01

    Full Text Available Abstract Background One of the many gene families that expanded in early vertebrate evolution is the neuropeptide (NPY receptor family of G-protein coupled receptors. Earlier work by our lab suggested that several of the NPY receptor genes found in extant vertebrates resulted from two genome duplications before the origin of jawed vertebrates (gnathostomes and one additional genome duplication in the actinopterygian lineage, based on their location on chromosomes sharing several gene families. In this study we have investigated, in five vertebrate genomes, 45 gene families with members close to the NPY receptor genes in the compact genomes of the teleost fishes Tetraodon nigroviridis and Takifugu rubripes. These correspond to Homo sapiens chromosomes 4, 5, 8 and 10. Results Chromosome regions with conserved synteny were identified and confirmed by phylogenetic analyses in H. sapiens, M. musculus, D. rerio, T. rubripes and T. nigroviridis. 26 gene families, including the NPY receptor genes, (plus 3 described recently by other labs showed a tree topology consistent with duplications in early vertebrate evolution and in the actinopterygian lineage, thereby supporting expansion through block duplications. Eight gene families had complications that precluded analysis (such as short sequence length or variable number of repeated domains and another eight families did not support block duplications (because the paralogs in these families seem to have originated in another time window than the proposed genome duplication events. RT-PCR carried out with several tissues in T. rubripes revealed that all five NPY receptors were expressed in the brain and subtypes Y2, Y4 and Y8 were also expressed in peripheral organs. Conclusion We conclude that the phylogenetic analyses and chromosomal locations of these gene families support duplications of large blocks of genes or even entire chromosomes. Thus, these results are consistent with two early vertebrate

  4. Cerebral cortex modulation of pain

    Institute of Scientific and Technical Information of China (English)

    Yu-feng XIE; Fu-quan HUO; Jing-shi TANG

    2009-01-01

    Pain is a complex experience encompassing sensory-discriminative, affective-motivational and cognitiv e-emotional com-ponents mediated by different mechanisms. Contrary to the traditional view that the cerebral cortex is not involved in pain perception, an extensive cortical network associated with pain processing has been revealed using multiple methods over the past decades. This network consistently includes, at least, the anterior cingulate cortex, the agranular insular cortex, the primary (SⅠ) and secondary somatosensory (SⅡ) cortices, the ventrolateral orbital cortex and the motor cortex. These corti-cal structures constitute the medial and lateral pain systems, the nucleus submedius-ventrolateral orbital cortex-periaque-ductal gray system and motor cortex system, respectively. Multiple neurotransmitters, including opioid, glutamate, GABA and dopamine, are involved in the modulation of pain by these cortical structures. In addition, glial cells may also be in-volved in cortical modulation of pain and serve as one target for pain management research. This review discusses recent studies of pain modulation by these cerebral cortical structures in animals and human.

  5. Using Gelatin Nanoparticle Mediated Intranasal Delivery of Neuropeptide Substance P to Enhance Neuro-Recovery in Hemiparkinsonian Rats.

    Directory of Open Access Journals (Sweden)

    Ying-Zheng Zhao

    Full Text Available Intranasal administration of phospholipid-based gelatin nanoparticles (GNP was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP on hemiparkinsonian rats.The SP-loaded gelatin nanoparticles (SP-GNP were prepared by a water-in-water emulsion method and possessed high stability, encapsulating efficiency and loading capacity. PC-12 cells were used to examine the growth enhancement of SP-GNP in vitro by MTT assays and flow cytometry (FCM. The therapeutic effects of SP-GNP on 6-hydroxydopamine (6-OHDA induced hemiparkinsonian rats were assessed by quantifying rotational behavior and the levels of tyrosine hydroxylase (TH, phosphorylated c-Jun protein (p-c-Jun and Caspase-3 (Cas-3 expressed in substantia nigra (SN region of hemiparkinsonian rats.PC-12 cells under SP-GNP treatment showed better cell viability and lower degree of apoptosis than those under SP solution treatment. Hemiparkinsonian rats under intranasal SP-GNP administration demonstrated better behavioral improvement, higher level of TH in SN along with much lower extent of p-c-Jun and Cas-3 than those under intranasal SP solution administration and intravenous SP-GNP administration.With the advantages of GNP and nose-to-brain pathway, SP can be effectively delivered into the damaged SN region and exhibit its neuro-recovery function through the inhibition on JNK pathway and dopaminergic neuron apoptosis.

  6. Activation of sensory cortex by imagined genital stimulation: an fMRI analysis

    Directory of Open Access Journals (Sweden)

    Nan J. Wise

    2016-10-01

    Full Text Available Background: During the course of a previous study, our laboratory made a serendipitous finding that just thinking about genital stimulation resulted in brain activations that overlapped with, and differed from, those generated by physical genital stimulation. Objective: This study extends our previous findings by further characterizing how the brain differentially processes physical ‘touch’ stimulation and ‘imagined’ stimulation. Design: Eleven healthy women (age range 29–74 participated in an fMRI study of the brain response to imagined or actual tactile stimulation of the nipple and clitoris. Two additional conditions – imagined dildo self-stimulation and imagined speculum stimulation – were included to characterize the effects of erotic versus non-erotic imagery. Results: Imagined and tactile self-stimulation of the nipple and clitoris each activated the paracentral lobule (the genital region of the primary sensory cortex and the secondary somatosensory cortex. Imagined self-stimulation of the clitoris and nipple resulted in greater activation of the frontal pole and orbital frontal cortex compared to tactile self-stimulation of these two bodily regions. Tactile self-stimulation of the clitoris and nipple activated the cerebellum, primary somatosensory cortex (hand region, and premotor cortex more than the imagined stimulation of these body regions. Imagining dildo stimulation generated extensive brain activation in the genital sensory cortex, secondary somatosensory cortex, hippocampus, amygdala, insula, nucleus accumbens, and medial prefrontal cortex, whereas imagining speculum stimulation generated only minimal activation. Conclusion: The present findings provide evidence of the potency of imagined stimulation of the genitals and that the following brain regions may participate in erogenous experience: primary and secondary sensory cortices, sensory-motor integration areas, limbic structures, and components of the

  7. Activation of sensory cortex by imagined genital stimulation: an fMRI analysis.

    Science.gov (United States)

    Wise, Nan J; Frangos, Eleni; Komisaruk, Barry R

    2016-01-01

    During the course of a previous study, our laboratory made a serendipitous finding that just thinking about genital stimulation resulted in brain activations that overlapped with, and differed from, those generated by physical genital stimulation. This study extends our previous findings by further characterizing how the brain differentially processes physical 'touch' stimulation and 'imagined' stimulation. Eleven healthy women (age range 29-74) participated in an fMRI study of the brain response to imagined or actual tactile stimulation of the nipple and clitoris. Two additional conditions - imagined dildo self-stimulation and imagined speculum stimulation - were included to characterize the effects of erotic versus non-erotic imagery. Imagined and tactile self-stimulation of the nipple and clitoris each activated the paracentral lobule (the genital region of the primary sensory cortex) and the secondary somatosensory cortex. Imagined self-stimulation of the clitoris and nipple resulted in greater activation of the frontal pole and orbital frontal cortex compared to tactile self-stimulation of these two bodily regions. Tactile self-stimulation of the clitoris and nipple activated the cerebellum, primary somatosensory cortex (hand region), and premotor cortex more than the imagined stimulation of these body regions. Imagining dildo stimulation generated extensive brain activation in the genital sensory cortex, secondary somatosensory cortex, hippocampus, amygdala, insula, nucleus accumbens, and medial prefrontal cortex, whereas imagining speculum stimulation generated only minimal activation. The present findings provide evidence of the potency of imagined stimulation of the genitals and that the following brain regions may participate in erogenous experience: primary and secondary sensory cortices, sensory-motor integration areas, limbic structures, and components of the 'reward system'. In addition, these results suggest a mechanism by which some individuals may

  8. The effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women.

    Science.gov (United States)

    Khoshdel, Abolfazl; Kheiri, Soleiman; Nasiri, Jafar; Tehran, Hoda Ahmari; Heidarian, Esfandiar

    2014-01-01

    Many pregnant Muslim women choose to fast during Ramadan every year worldwide. This study aimed to examine the effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women and find whether fasting during pregnancy could have a negative effect on the health of mothers and fetuses. This cross-sectional study was conducted on 39 healthy volunteer fasting pregnant women. Serum leptin, neuropeptide Y, insulin levels, body mass index and weight were measured five times on 0, 7th, 14th and 28th days of Ramadan and on the 14th day post-Ramadan. The data were analyzed by SPSS software (version 11.5) using repeated measures ANOVA to find whether any changes occurred in the variables of interest during the study, and Pearson correlation coefficient was used to examine the relations among the variables. A significant change in fasting blood sugar, neuropeptide Y and leptin was observed during the study (pRamadan and increased after Ramadan, with the lowest value at the end of Ramadan. Neuropeptide Y increased both during Ramadan and two weeks after Ramadan. Also, leptin decreased significantly two weeks after Ramadan compared to the end of Ramadan. No significant change was observed in insulin level during the study (p>0.05). The result of this study revealed the important role of leptin and neuropeptide Y in the long term regulation of energy balance in pregnant women with chronic diurnal fasting, and it further revealed that Ramadan fasting did not significantly change the serum insulin level.

  9. Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal

    NARCIS (Netherlands)

    Riem, M.M.E.; van IJzendoorn, M.H.; Tops, M.; Boksem, M.A.S.; Rombouts, S.A.R.B.; Bakermans-Kranenburg, M.J.

    2013-01-01

    The neuropeptide oxytocin has been implicated in a variety of social processes. However, recent studies indicate that oxytocin does not enhance prosocial behavior in all people in all circumstances. Here, we investigate effects of intranasal oxytocin administration on intrinsic functional brain

  10. Neuropeptide B in Nile tilapia Oreochromis niloticus: molecular cloning and its effects on the regulation of food intake and mRNA expression of growth hormone and prolactin.

    Science.gov (United States)

    Yang, Lu; Sun, Caiyun; Li, Wensheng

    2014-05-01

    Neuropeptide B (NPB) regulates food intake, energy homeostasis and hormone secretion in mammals via two G-protein coupled receptors, termed as GPR 7 and GPR 8. However, there is no study that reports the function of NPB in teleosts. In this study, the full-length cDNA of prepro-NPB with the size of 663bp was cloned from the hypothalamus of Nile tilapia. The CDS of the prepro-NPB is 387bp which encodes a precursor protein with the size of 128a.a. This precursor contains a mature peptide with the size of 29a.a, and it was named as NPB29. Tissue distribution study showed that this gene was mainly expressed in different parts of brain, especially in the diencephalon as well as hypothalamus, and the spinal cord in Nile tilapia. Fasting significantly stimulated the mRNA expression of NPB in the brain area without hypothalamus, and refeeding after fasting for 3 and 14days also showed similar effects on NPB expression. While, only short-term fasting (3days) and refeeding after fasting for 7 and 14days induced mRNA expression of NPB in the hypothalamus. Intraperitoneal (i.p.) injection of NPB remarkably elevated the mRNA expression of hypothalamic neuropeptide Y (NPY), cholecystokinin 1 (CCK1) and pituitary prolactin (PRL), whereas significantly inhibited growth hormone (GH) expression in pituitary. These observations in the present study suggested that NPB may participate in the regulation of feeding and gene expression of pituitary GH and PRL in Nile tilapia. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Arginine Vasotocin, the Social Neuropeptide of Amphibians and Reptiles.

    Science.gov (United States)

    Wilczynski, Walter; Quispe, Maricel; Muñoz, Matías I; Penna, Mario

    2017-01-01

    Arginine vasotocin (AVT) is the non-mammalian homolog of arginine vasopressin (AVP) and, like vasopressin, serves as an important modulator of social behavior in addition to its peripheral functions related to osmoregulation, reproductive physiology, and stress hormone release. In amphibians and reptiles, the neuroanatomical organization of brain AVT cells and fibers broadly resembles that seen in mammals and other taxa. Both parvocellular and magnocellular AVT-containing neurons are present in multiple populations located mainly in the basal forebrain from the accumbens-amygdala area to the preoptic area and hypothalamus, from which originate widespread fiber connections spanning the brain with a particularly heavy innervation of areas associated with social behavior and decision-making. As for mammalian AVP, AVT is present in greater amounts in males in many brain areas, and its presence varies seasonally, with hormonal state, and in males with differing social status. AVT's social influence is also conserved across herpetological taxa, with significant effects on social signaling and aggression, and, based on the very small number of studies investigating more complex social behaviors in amphibians and reptiles, AVT may also modulate parental care and social bonding when it is present in these vertebrates. Within this conserved pattern, however, both AVT anatomy and social behavior effects vary significantly across species. Accounting for this diversity represents a challenge to understanding the mechanisms by which AVT exerts its behavioral effects, as well are a potential tool for discerning the structure-function relationships underlying AVT's many effects on behavior.

  12. Prefrontal Cortex, Emotion, and Approach/Withdrawal Motivation.

    Science.gov (United States)

    Spielberg, Jeffrey M; Stewart, Jennifer L; Levin, Rebecca L; Miller, Gregory A; Heller, Wendy

    2008-01-01

    This article provides a selective review of the literature and current theories regarding the role of prefrontal cortex, along with some other critical brain regions, in emotion and motivation. Seemingly contradictory findings have often appeared in this literature. Research attempting to resolve these contradictions has been the basis of new areas of growth and has led to more sophisticated understandings of emotional and motivational processes as well as neural networks associated with these processes. Progress has, in part, depended on methodological advances that allow for increased resolution in brain imaging. A number of issues are currently in play, among them the role of prefrontal cortex in emotional or motivational processes. This debate fosters research that will likely lead to further refinement of conceptualizations of emotion, motivation, and the neural processes associated with them.

  13. Sensory experience modifies feature map relationships in visual cortex

    Science.gov (United States)

    Cloherty, Shaun L; Hughes, Nicholas J; Hietanen, Markus A; Bhagavatula, Partha S

    2016-01-01

    The extent to which brain structure is influenced by sensory input during development is a critical but controversial question. A paradigmatic system for studying this is the mammalian visual cortex. Maps of orientation preference (OP) and ocular dominance (OD) in the primary visual cortex of ferrets, cats and monkeys can be individually changed by altered visual input. However, the spatial relationship between OP and OD maps has appeared immutable. Using a computational model we predicted that biasing the visual input to orthogonal orientation in the two eyes should cause a shift of OP pinwheels towards the border of OD columns. We then confirmed this prediction by rearing cats wearing orthogonally oriented cylindrical lenses over each eye. Thus, the spatial relationship between OP and OD maps can be modified by visual experience, revealing a previously unknown degree of brain plasticity in response to sensory input. DOI: http://dx.doi.org/10.7554/eLife.13911.001 PMID:27310531

  14. TRH regulates action potential shape in cerebral cortex pyramidal neurons.

    Science.gov (United States)

    Rodríguez-Molina, Víctor; Patiño, Javier; Vargas, Yamili; Sánchez-Jaramillo, Edith; Joseph-Bravo, Patricia; Charli, Jean-Louis

    2014-07-07

    Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5µM of TRH induced a small increase in spike half-width, while 1 and 5µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5µM TRH; layer II neurons response was small. The effect of 1µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Orosensory and Homeostatic Functions of the Insular Taste Cortex.

    Science.gov (United States)

    de Araujo, Ivan E; Geha, Paul; Small, Dana M

    2012-03-01

    The gustatory aspect of the insular cortex is part of the brain circuit that controls ingestive behaviors based on chemosensory inputs. However, the sensory properties of foods are not restricted to taste and should also include salient features such as odor, texture, temperature, and appearance. Therefore, it is reasonable to hypothesize that specialized circuits within the central taste pathways must be involved in representing several other oral sensory modalities in addition to taste. In this review, we evaluate current evidence indicating that the insular gustatory cortex functions as an integrative circuit, with taste-responsive regions also showing heightened sensitivity to olfactory, somatosensory, and even visual stimulation. We also review evidence for modulation of taste-responsive insular areas by changes in physiological state, with taste-elicited neuronal responses varying according to the nutritional state of the organism. We then examine experimental support for a functional map within the insular cortex that might reflect the various sensory and homeostatic roles associated with this region. Finally, we evaluate the potential role of the taste insular cortex in weight-gain susceptibility. Taken together, the current experimental evidence favors the view that the insular gustatory cortex functions as an orosensory integrative system that not only enables the formation of complex flavor representations but also mediates their modulation by the internal state of the body, playing therefore a central role in food intake regulation.

  16. Ventromedial prefrontal cortex mediates visual attention during facial emotion recognition.

    Science.gov (United States)

    Wolf, Richard C; Philippi, Carissa L; Motzkin, Julian C; Baskaya, Mustafa K; Koenigs, Michael

    2014-06-01

    The ventromedial prefrontal cortex is known to play a crucial role in regulating human social and emotional behaviour, yet the precise mechanisms by which it subserves this broad function remain unclear. Whereas previous neuropsychological studies have largely focused on the role of the ventromedial prefrontal cortex in higher-order deliberative processes related to valuation and decision-making, here we test whether ventromedial prefrontal cortex may also be critical for more basic aspects of orienting attention to socially and emotionally meaningful stimuli. Using eye tracking during a test of facial emotion recognition in a sample of lesion patients, we show that bilateral ventromedial prefrontal cortex damage impairs visual attention to the eye regions of faces, particularly for fearful faces. This finding demonstrates a heretofore unrecognized function of the ventromedial prefrontal cortex-the basic attentional process of controlling eye movements to faces expressing emotion. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Interpretation of the function of the striate cortex

    Science.gov (United States)

    Garner, Bernardette M.; Paplinski, Andrew P.

    2000-04-01

    Biological neural networks do not require retraining every time objects move in the visual field. Conventional computer neural networks do not share this shift-invariance. The brain compensates for movements in the head, body, eyes and objects by allowing the sensory data to be tracked across the visual field. The neurons in the striate cortex respond to objects moving across the field of vision as is seen in many experiments. It is proposed, that the neurons in the striate cortex allow continuous angle changes needed to compensate for changes in orientation of the head, eyes and the motion of objects in the field of vision. It is hypothesized that the neurons in the striate cortex form a system that allows for the translation, some rotation and scaling of objects and provides a continuity of objects as they move relative to other objects. The neurons in the striate cortex respond to features which are fundamental to sight, such as orientation of lines, direction of motion, color and contrast. The neurons that respond to these features are arranged on the cortex in a way that depends on the features they are responding to and on the area of the retina from which they receive their inputs.

  18. Orbitofrontal cortex function and structure in depression.

    Science.gov (United States)

    Drevets, Wayne C

    2007-12-01

    The orbitofrontal cortex (OFC) has been implicated in the pathophysiology of major depression by evidence obtained using neuroimaging, neuropathologic, and lesion analysis techniques. The abnormalities revealed by these techniques show a regional specificity, and suggest that some OFC regions which appear cytoarchitectonically distinct also are functionally distinct with respect to mood regulation. For example, the severity of depression correlates inversely with physiological activity in parts of the posterior lateral and medial OFC, consistent with evidence that dysfunction of the OFC associated with cerebrovascular lesions increases the vulnerability for developing the major depressive syndrome. The posterior lateral and medial OFC function may also be impaired in individuals who develop primary mood disorders, as these patients show grey-matter volumetric reductions, histopathologic abnormalities, and altered hemodynamic responses to emotionally valenced stimuli, probabilistic reversal learning, and reward processing. In contrast, physiological activity in the anteromedial OFC situated in the ventromedial frontal polar cortex increases during the depressed versus the remitted phases of major depressive disorder to an extent that is positively correlated with the severity of depression. Effective antidepressant treatment is associated with a reduction in activity in this region. Taken together these data are compatible with evidence from studies in experimental animals indicating that some orbitofrontal and medial prefrontal cortex regions function to inhibit, while others function to enhance, emotional expression. Alterations in the functional balance between these regions and the circuits they form with anatomically related areas of the temporal lobe, striatum, thalamus, and brain stem thus may underlie the pathophysiology of mood disorders, such as major depression.

  19. Golgi Analysis of Neuron Morphology in the Presumptive Somatosensory Cortex and Visual Cortex of the Florida Manatee (Trichechus manatus latirostris).

    Science.gov (United States)

    Reyes, Laura D; Harland, Tessa; Reep, Roger L; Sherwood, Chet C; Jacobs, Bob

    2016-01-01

    The current study investigates neuron morphology in presumptive primary somatosensory (S1) and primary visual (V1) cortices of the Florida manatee (Trichechus manatus latirostris) as revealed by Golgi impregnation. Sirenians, including manatees, have an aquatic lifestyle, a large body size, and a relatively large lissencephalic brain. The present study examines neuron morphology in 3 cortical areas: in S1, dorsolateral cortex area 1 (DL1) and cluster cortex area 2 (CL2) and in V1, dorsolateral cortex area 4 (DL4). Neurons exhibited a variety of morphological types, with pyramidal neurons being the most common. The large variety of neuron types present in the manatee cortex was comparable to that seen in other eutherian mammals, except for rodents and primates, where pyramid-shaped neurons predominate. A comparison between pyramidal neurons in S1 and V1 indicated relatively greater dendritic branching in S1. Across all 3 areas, the dendritic arborization pattern of pyramidal neurons was also similar to that observed previously in the afrotherian rock hyrax, cetartiodactyls, opossums, and echidnas but did not resemble the widely bifurcated dendrites seen in the large-brained African elephant. Despite adaptations for an aquatic environment, manatees did not share specific neuron types such as tritufted and star-like neurons that have been found in cetaceans. Manatees exhibit an evolutionarily primitive pattern of cortical neuron morphology shared with most other mammals and do not appear to have neuronal specializations for an aquatic niche. © 2016 S. Karger AG, Basel.

  20. Neurocomputational Consequences of Evolutionary Connectivity Changes in Perisylvian Language Cortex

    OpenAIRE

    Schomers, M.R.; Garagnani, M.; Pulvermüller, F.

    2017-01-01

    The human brain sets itself apart from that of its primate relatives by specific neuroanatomical features, especially the strong linkage of left perisylvian language areas (frontal and temporal cortex) by way of the arcuate fasciculus (AF). AF connectivity has been shown to correlate with verbal working memory?a specifically human trait providing the foundation for language abilities?but a mechanistic explanation of any related causal link between anatomical structure and cognitive function i...

  1. Chemosensory Learning in the Cortex

    Directory of Open Access Journals (Sweden)

    Edmund eRolls

    2011-09-01

    Full Text Available Taste is a primary reinforcer. Olfactory-taste and visual-taste association learning takes place in the primate including human orbitofrontal cortex to build representations of flavour. Rapid reversal of this learning can occur using a rule-based learning system that can be reset when an expected taste or flavour reward is not obtained, that is by negative reward prediction error, to which a population of neurons in the orbitofrontal cortex responds. The representation in the orbitofrontal cortex but not the primary taste or olfactory cortex is of the reward value of the visual / olfactory / taste / input as shown by devaluation experiments in which food is fed to satiety, and by correlations with the activations with subjective pleasantness ratings in humans. Sensory-specific satiety for taste, olfactory, visual, and oral somatosensory inputs produced by feeding a particular food to satiety are implemented it is proposed by medium-term synaptic adaptation in the orbitofrontal cortex. Cognitive factors, including word-level descriptions, modulate the representation of the reward value of food in the orbitofrontal cortex, and this effect is learned it is proposed by associative modification of top-down synapses onto neurons activated by bottom-up taste and olfactory inputs when both are active in the orbitofrontal cortex. A similar associative synaptic learning process is proposed to be part of the mechanism for the top-down attentional control to the reward value vs the sensory properties such as intensity of taste and olfactory inputs in the orbitofrontal cortex, as part of a biased activation theory of selective attention.

  2. Frequency specific modulation of human somatosensory cortex

    Directory of Open Access Journals (Sweden)

    Matteo eFeurra

    2011-02-01

    Full Text Available Oscillatory neuronal activities are commonly observed in response to sensory stimulation. However, their functional roles are still the subject of debate. One way to probe the roles of oscillatory neural activities is to deliver alternating current to the cortex at biologically relevant frequencies and examine whether such stimulation influences perception and cognition. In this study, we tested whether transcranial alternating current stimulation (tACS over the primary somatosensory cortex (SI could elicit tactile sensations in humans in a frequency dependent manner. We tested the effectiveness of tACS over SI at frequency bands ranging from 2 to 70 Hz. Our results show that stimulation in alpha (10-14 Hz and high gamma (52-70 Hz frequency range produces a tactile sensation in the contralateral hand. A weaker effect was also observed for beta (16-20 Hz stimulation. These findings highlight the frequency-dependency of effective tACS over SI with the effective frequencies corresponding to those observed in previous EEG/MEG studies of tactile perception. Our present study suggests that tACS could be used as a powerful online stimulation technique to reveal the causal roles of oscillatory brain activities.

  3. Cognitive Control Signals in Posterior Cingulate Cortex

    Directory of Open Access Journals (Sweden)

    Benjamin eHayden

    2010-12-01

    Full Text Available Efficiently shifting between tasks is a central function of cognitive control. The role of the default network—a constellation of areas with high baseline activity that declines during task performance—in cognitive control remains poorly understood. We hypothesized that task switching demands cognitive control to shift the balance of processing towards the external world, and therefore predicted that switching between the two tasks would require suppression of activity of neurons within the CGp. To test this idea, we recorded the activity of single neurons in posterior cingulate cortex (CGp, a central node in the default network, in monkeys performing two interleaved tasks. As predicted, we found that basal levels of neuronal activity were reduced following a switch from one task to another and gradually returned to pre-switch baseline on subsequent trials. We failed to observe these effects in lateral intraparietal cortex (LIP, part of the dorsal fronto-parietal cortical attention network directly connected to CGp. These findings indicate that suppression of neuronal activity in CGp facilitates cognitive control, and suggest that activity in the default network reflects processes that directly compete with control processes elsewhere in the brain..

  4. MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject

    DEFF Research Database (Denmark)

    Ioannides, Andreas A; Liu, Lichan; Poghosyan, Vahe

    2013-01-01

    magnetoencephalography (MEG) data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified...... reproducible brain responses in the primary somatosensory (S1) and motor (M1) cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45-70 Hz activity at latencies of 20-50 ms in S1 and M1, and posterior parietal cortex Brodmann...... of information through this pathway occurred in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first...

  5. Cortex and amygdala morphology in psychopathy.

    Science.gov (United States)

    Boccardi, Marina; Frisoni, Giovanni B; Hare, Robert D; Cavedo, Enrica; Najt, Pablo; Pievani, Michela; Rasser, Paul E; Laakso, Mikko P; Aronen, Hannu J; Repo-Tiihonen, Eila; Vaurio, Olli; Thompson, Paul M; Tiihonen, Jari

    2011-08-30

    Psychopathy is characterized by abnormal emotional processes, but only recent neuroimaging studies have investigated its cerebral correlates. The study aim was to map local differences of cortical and amygdalar morphology. Cortical pattern matching and radial distance mapping techniques were used to analyze the magnetic resonance images of 26 violent male offenders (age: 32±8) with psychopathy diagnosed using the Psychopathy Checklist-Revised (PCL-R) and no schizophrenia spectrum disorders, and in matched controls (age: 35± sp="0.12"/>11). The cortex displayed up to 20% reduction in the orbitofrontal and midline structures (corrected pamygdala (corrected p=0.05 on the right; and symmetrical pattern on the left). Psychopathy features specific morphology of the main cerebral structures involved in cognitive and emotional processing, consistent with clinical and functional data, and with a hypothesis of an alternative evolutionary brain development. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Brain-computer interfaces

    DEFF Research Database (Denmark)

    Treder, Matthias S.; Miklody, Daniel; Blankertz, Benjamin

    quality measure'. We were able to show that for stimuli close to the perceptual threshold, there was sometimes a discrepancy between overt responses and brain responses, shedding light on subjects using different response criteria (e.g., more liberal or more conservative). To conclude, brain-computer...... of perceptual and cognitive biases. Furthermore, subjects can only report on stimuli if they have a clear percept of them. On the other hand, the electroencephalogram (EEG), the electrical brain activity measured with electrodes on the scalp, is a more direct measure. It allows us to tap into the ongoing neural...... auditory processing stream. In particular, it can tap brain processes that are pre-conscious or even unconscious, such as the earliest brain responses to sounds stimuli in primary auditory cortex. In a series of studies, we used a machine learning approach to show that the EEG can accurately reflect...

  7. Interrelationship of brain-functions with cardiovascular regulations

    International Nuclear Information System (INIS)

    Rahman, M.K.

    1993-03-01

    Neurotransmitters and neuropeptides are involved in the regulation of nervous function, behaviour, emotion, sex, sleep, mood of higher animals including the humans. They act and they occur simultaneously in the brain as neurotransmitters or neuromodulators and in plasma as circulating hormones. The direct regulatory interactions of a given substance in the blood and in the brain are still unknown, but some results have already been published regarding these relationships. The present paper briefly describes the systematic review-type studies on the interrelationship of the brain functions and the cardiovascular regulation. 35 refs, 7 figs, 1 tab

  8. Multiple distinct subtypes of GABAergic neurons in mouse visual cortex identified by triple immunostaining

    Directory of Open Access Journals (Sweden)

    Yuri Gonchar

    2008-03-01

    Full Text Available The majority of cortical interneurons use GABA (gamma amino butyric acid as inhibitory neurotransmitter. GABAergic neurons are morphologically, connectionally, electrically and chemically heterogeneous. In rat cerebral cortex three distinct groups of GABAergic interneurons have been identifi ed by the expression of parvalbumin (PV, calretinin (CR and somatostatin (SOM. Recent studies in mouse cerebral cortex have revealed a different organization in which the CR and SOM populations are partially overlapping. Because CR and SOM neurons derive from different progenitors located in different embryonic structures, the coexpression of CR + SOM suggests that the chemical differentiation of interneurons is regulated postmitotically. Here, we have taken an important fi rst step towards understanding this process by triple immunostaining mouse visual cortex with a panel of antibodies, which has been used extensively for classifying developing interneurons. We have found at least 13 distinct groups of GABAergic neurons which include PV, CR, SOM, CCK (cholecystokinin, CR + SOM, CR + NPY (neuropeptide Y, CR + VIP (vasointestinal polypeptide, SOM + NPY, SOM + VIP, VIP + ChAT (choline acetyltransferase, CCK + NPY, CR + SOM + NPY and CR + SOM + VIP expressing cells. Triple immunostaining with PV, CR and SOM antibodies during postnatal development further showed that PV is never colocalized with CR and SOM. Importantly, expression of SOM and CR + SOM developed after the percentage of CR cells that do not express SOM has reached the mature level, suggesting that the chemical differentiation of SOM and CR + SOM neurons is a postnatal event, which may be controlled by transcriptional regulation.

  9. Arginine Vasotocin, the Social Neuropeptide of Amphibians and Reptiles

    Science.gov (United States)

    Wilczynski, Walter; Quispe, Maricel; Muñoz, Matías I.; Penna, Mario

    2017-01-01

    Arginine vasotocin (AVT) is the non-mammalian homolog of arginine vasopressin (AVP) and, like vasopressin, serves as an important modulator of social behavior in addition to its peripheral functions related to osmoregulation, reproductive physiology, and stress hormone release. In amphibians and reptiles, the neuroanatomical organization of brain AVT cells and fibers broadly resembles that seen in mammals and other taxa. Both parvocellular and magnocellular AVT-containing neurons are present in multiple populations located mainly in the basal forebrain from the accumbens–amygdala area to the preoptic area and hypothalamus, from which originate widespread fiber connections spanning the brain with a particularly heavy innervation of areas associated with social behavior and decision-making. As for mammalian AVP, AVT is present in greater amounts in males in many brain areas, and its presence varies seasonally, with hormonal state, and in males with differing social status. AVT’s social influence is also conserved across herpetological taxa, with significant effects on social signaling and aggression, and, based on the very small number of studies investigating more complex social behaviors in amphibians and reptiles, AVT may also modulate parental care and social bonding when it is present in these vertebrates. Within this conserved pattern, however, both AVT anatomy and social behavior effects vary significantly across species. Accounting for this diversity represents a challenge to understanding the mechanisms by which AVT exerts its behavioral effects, as well are a potential tool for discerning the structure-function relationships underlying AVT’s many effects on behavior. PMID:28824546