Home About us Contact
|
Home About us Contact | ||
|
|
||
GABAergic System (gabaergic + system)
Selected AbstractsInflux of calcium through L-type calcium channels in early postnatal regulation of chloride transporters in the rat hippocampusDEVELOPMENTAL NEUROBIOLOGY, Issue 13 2009Jennifer G. Bray Abstract During the early postnatal period, GABAB receptor activation facilitates L-type calcium current in rat hippocampus. One developmental process that L-type current may regulate is the change in expression of the K+Cl, co-transporter (KCC2) and N+K+2Cl, co-transporter (NKCC1), which are involved in the maturation of the GABAergic system. The present study investigated the connection between L-type current, GABAB receptors, and expression of chloride transporters during development. The facilitation of L-type current by GABAB receptors is more prominent in the second week of development, with the highest percentage of cells exhibiting facilitation in cultures isolated from 7 day old rats (37.5%). The protein levels of KCC2 and NKCC1 were investigated to determine the developmental timecourse of expression as well as expression following treatment with an L-type channel antagonist and a GABAB receptor agonist. The time course of both chloride transporters in culture mimics that seen in hippocampal tissue isolated from various ages. KCC2 levels increased drastically in the first two postnatal weeks while NKCC1 remained relatively stable, suggesting that the ratio of the chloride transporters is important in mediating the developmental change in chloride reversal potential. Treatment of cultures with the L-type antagonist nimodipine did not affect protein levels of NKCC1, but significantly decreased the upregulation of KCC2 during the first postnatal week. In addition, calcium current facilitation occurs slightly before the large increase in KCC2 expression. These results suggest that the expression of KCC2 is regulated by calcium influx through L-type channels in the early postnatal period in hippocampal neurons. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source] Role of GABAA inhibition in modulation of pyramidal tract neuron activity during postural correctionsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2007Zinaida A. Tamarova Abstract In a previous study we demonstrated that the activity of pyramidal tract neurons (PTNs) of the motor cortex is modulated in relation to postural corrections evoked by periodical tilts of the animal. The modulation included an increase in activity in one phase of the tilt cycle and a decrease in the other phase. It is known that the motor cortex contains a large population of inhibitory GABAergic neurons. How do these neurons participate in periodic modulation of PTNs? The goal of this study was to investigate the role of GABAA inhibitory neurons of the motor cortex in the modulation of postural-related PTN activity. Using extracellular electrodes with attached micropipettes, we recorded the activity of PTNs in cats maintaining balance on a tilting platform both before and after iontophoretic application of the GABAA receptor antagonists gabazine or bicuculline. The tilt-related activity of 93% of PTNs was affected by GABAA receptor antagonists. In 88% of cells, peak activity increased by 75 ± 50% (mean ± SD). In contrast, the trough activity changed by a much smaller value and almost as many neurons showed a decrease as showed an increase. In 73% of the neurons, the phase position of the peak activity did not change or changed by no more than 0.1 of a cycle. We conclude that the GABAergic system of the motor cortex reduces the posture-related responses of PTNs but has little role in determining their response timing. [source] Stress and GABAA receptorsJOURNAL OF NEUROCHEMISTRY, Issue 5 2010Kelly J. Skilbeck J. Neurochem. (2010) 112, 1115,1130. Abstract GABAA receptors are sensitive to subtle changes in the environment in both early-life and adulthood. These neurochemical responses to stress in adulthood are sex-dependent. Acute stress induces rapid changes in GABAA receptors in experimental animals, with the direction of the changes varying according to the sex of the animals and the stress-paradigm studied. These rapid alterations are of particular interest as they provide an example of fast neurotransmitter system plasticity that may be mediated by stress-induced increases in neurosteroids, perhaps via effects on phosphorylation and/or receptor trafficking. Interestingly, some studies have also provided evidence for long-lasting changes in GABAA receptors as a result of exposure to stressors in early-life. The short- and long-term stress sensitivity of the GABAergic system implicates GABAA receptors in the non-genetic etiology of psychiatric illnesses such as depression and schizophrenia in which stress may be an important factor. [source] GABAA receptors in aging and Alzheimer's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 4 2007Robert A. Rissman Abstract In this article we present a comprehensive review of relevant research and reports on the GABAA receptor in the aged and Alzheimer's disease (AD) brain. In comparison to glutamatergic and cholinergic systems, the GABAergic system is relatively spared in AD, but the precise mechanisms underlying differential vulnerability are not well understood. Using several methods, investigations demonstrate that despite resistance of the GABAergic system to neurodegeneration, particular subunits of the GABAA receptor are altered with age and AD, which can induce compensatory increases in GABAA receptor subunits within surrounding cells. We conclude that although aging- and disease-related changes in GABAA receptor subunits may be modest, the mechanisms that compensate for these changes may alter the pharmacokinetic and physiological properties of the receptor. It is therefore crucial to understand the subunit composition of individual GABAA receptors in the diseased brain when developing therapeutics that act at these receptors. [source] Intracerebroventricular administration of GABA-A and GABA-B receptor antagonists attenuate feeding and sleeping-like behavior induced by L -pipecolic acid in neonatal chicksJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003T. Takagi Abstract It has been demonstrated that L -pipecolic acid (L -PA), a major metabolic intermediate of L -lysine (L -Lys) in the mammalian and chicken brain, is involved in the functioning of the GABAergic system. A previous study has shown that intracerebroventricular (i.c.v.) injection of L -PA suppressed feeding and induced sleep-like behavior in neonatal chicks; however, the precise relationship between the GABAergic system and L -PA has not been clarified. In the present study, the role of the GABA-A or GABA-B receptors in the suppression of food intake and induction of sleeping-like behavior by L -PA was investigated. Chicks were injected i.c.v. with the GABA-A antagonist picrotoxin or GABA-B antagonist CGP54626 along with L -PA. Although suppression of food intake by L -PA was restored partially by co-injection with CGP54626, but not picrotoxin, sleep-like behavior induced by L -PA was suppressed significantly by both antagonists. These results suggested that L -PA activated both GABA-A and GABA-B receptors, and GABA-B receptors alone contributed to food intake whereas both receptors contributed to sleep-like behavior. © 2003 Wiley-Liss, Inc. [source] Protective effect of BR-16A, a polyherbal preparation against social isolation stress: possible GABAergic mechanismPHYTOTHERAPY RESEARCH, Issue 7 2006Anil Kumar Abstract The antistress effects of BR-16A, a polyherbal preparation and its interaction with GABAergic modulators against social isolation-induced stress were investigated in the present study. Isolation stress was induced by keeping the mice (Laca strain) individually in each cage for 3 weeks and various drug treatments were given for a period of 5 days before the start of the experiments. The various behavioural parameters examined included pentobarbitone-induced sleep (sleep latency and duration), analgesia (tail-ßick test) and locomotor activity, respectively. BR-16A (100 mg/kg and 200 mg/kg) treatment for 5 days significantly reversed the social isolation stress-induced prolongation of onset and decrease in pentobarbitone-induced sleep, increased total motor activity and stress-induced antinociception. When diazepam (0.5 mg/kg), a benzodiazepine agonist, was co-administered with BR-16A (100 mg/kg), it significantly potentiated the reversal of pentobarbitone-induced shortening of sleep time effects; increased locomotor activity and stress induced antinociceptive effects. However, the sleep latency was not decreased significantly. Further, ßumazenil (2 mg/kg), a benzodiazepine receptor antagonist and FG 7142 (10 mg/kg), an inverse agonist, when co-administered with BR-16A (100 mg/kg), showed no significant reversal on pentobarbitone-induced hypnosis, locomotor activity and social isolation-induced antinociception compared with their effects per se. The present study demonstrated the antistress effects of BR-16A preparation against social isolation-induced stress. The present study also suggests that the GABAergic system may be involved in its antistress effect. Copyright © 2006 John Wiley & Sons, Ltd. [source] Molecular mechanisms supporting a paracrine role of GABA in rat adrenal medullary cellsTHE JOURNAL OF PHYSIOLOGY, Issue 20 2008Hidetada Matsuoka GABA is known to produce membrane depolarization and secretion in adrenal medullary (AM) cells in various species. However, whether the GABAergic system is intrinsic or extrinsic or both in the adrenal medulla and the role that GABA plays are controversial. Therefore, these issues were addressed by combining a biochemical and functional analysis. Glutamic acid decarboxylase (GAD), a GABA synthesizing enzyme, and vesicular GABA transporter (VGAT) were expressed in rat AM cells at the mRNA and protein levels, and the adrenal medulla had no nerve fibre-like structures immunoreactive to an anti-GAD Ab. The double staining for VGAT and chromogranin A indicates that GABA was stored in chromaffin granules. The ,1, ,3, ,2/3, ,2 and , subunits of GABAA receptors were identified in AM cells at the mRNA and protein levels. Pharmacological properties of GABA-induced Cl, currents, immunoprecipitation experiments and immunocytochemistry indicated the expression of not only ,2-, but also ,-containing GABAA receptors, which have higher affinities for GABA and neurosteroids. Expression of GATs, which are involved in the clearance of GABA at GABAergic synapses, were conspicuously suppressed in the adrenal medulla, compared with expression levels of GABAA receptors. Increases in Ca2+ signal in AM cells evoked trans-synaptically by nerve stimulation were suppressed during the response to GABA, and this suppression was attributed to the shunt effect of the GABA-induced increase in conductance. Overall Ca2+ responses to electrical stimulation and GABA in AM cells were larger or smaller than those to electrical stimulation alone, depending on the frequency of stimulation. The results indicate that GABA functions as a paracrine in rat AM cells and this function may be supported by the suppression of GAT expression and the expression of not only ,2-, but also ,-GABAA receptors. [source] Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism: an in situ hybridization studyAUTISM RESEARCH, Issue 1 2009Jane Yip Abstract The laterally positioned dentate nuclei lie in a key position in the cerebellum to receive input from Purkinje cells in the lateral cerebellar hemisphere participating in both motor and cognitive functions. Although neuropathology of the four cerebellar nuclei using Nissl staining has been qualitatively reported in children and adults with autism, surprisingly the dentate nuclei appeared less affected despite reported reductions in Purkinje cells in the posterolateral cerebellar hemisphere. To determine any underlying abnormalities in the critically important GABAergic system, the rate-limiting GABA synthesizing enzyme, glutamic acid decarboxylase (GAD) type 65 was measured via in situ hybridization histochemistry in dentate somata. GAD65 mRNA labeling revealed two distinct subpopulations of neurons in adult control and autism postmortem brains: small-sized cells (about 10,12,µm in diameter, presumed interneurons) and larger-sized neurons (about 18,20,µm in diameter, likely feedback to inferior olivary neurons). A mean 51% reduction in GAD65 mRNA levels was found in the larger labeled cells in the autistic group compared with the control group (P=0.009; independent t -test) but not in the smaller cell subpopulation. This suggests a disturbance in the intrinsic cerebellar circuitry in the autism group potentially interfering with the synchronous firing of inferior olivary neurons, and the timing of Purkinje cell firing and inputs to the dentate nuclei. Disturbances in critical neural substrates within these key circuits could disrupt afferents to motor and/or cognitive cerebral association areas in the autistic brain likely contributing to the marked behavioral consequences characteristic of autism. [source] Novel targets for valproic acid: up-regulation of melatonin receptors and neurotrophic factors in C6 glioma cellsJOURNAL OF NEUROCHEMISTRY, Issue 5 2005Lyda M. Rincón Castro Abstract Valproic acid (VPA) is a potent anti-epileptic and effective mood stabilizer. It is known that VPA enhances central GABAergic activity and activates the mitogen-activated protein kinase,extracellular signal-regulated kinase (MAPK,ERK) pathway. It can also inhibit various isoforms of the enzyme, histone deacetylase (HDAC), which is associated with modulation of gene transcription. Recent in vivo studies indicate a neuroprotective role for VPA, which has been found to up-regulate the expression of brain-derived neurotrophic factor (BDNF) in the rat brain. Given the interaction between the pineal hormone, melatonin, and GABAergic systems in the central nervous system, the effects of VPA on the expression of the mammalian melatonin receptor subtypes, MT1 and MT2, were examined in rat C6 glioma cells. The effects of VPA on the expression of glial cell line-derived neurotrophic factor (GDNF) and BDNF were also examined. RT-PCR studies revealed a significant induction of melatonin MT1 receptor mRNA in C6 cells following treatment with 3 or 5 mm VPA for 24 h or 5 mm VPA for 48 h. Western analysis and immunocytochemical detection confirmed that the VPA-induced increase in MT1 mRNA results in up-regulation of MT1 protein expression. Blockade of the MAPK,ERK pathway by PD98059 enhanced the effect of VPA on MT1 expression, suggesting a negative role for this pathway in MT1 receptor regulation. In addition, significant increases in BDNF, GDNF and HDAC mRNA expression were observed after treatment with VPA for 24 or 48 h. Taken together, the present findings suggest that the neuroprotective properties of VPA involve modulation of neurotrophic factors and receptors for melatonin, which is also thought to play a role in neuroprotection. Moreover, the foregoing suggests that combinations of VPA and melatonin could provide novel therapeutic strategies in neurological and psychiatric disorders. [source] | |||||||||||||