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Amino Butyric Acid (amino + butyric_acid)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	42%

Kinds of Amino Butyric Acid

gamma amino butyric acid

Selected Abstracts

Association Between Alcoholism and ,-Amino Butyric Acid ,2 Receptor Subtype in a Russian Population

ALCOHOLISM, Issue 4 2005
Jaakko Lappalainen
Background: Two recent large genetic studies in the US population have reported association between genetic variation in ,-amino butyric acid ,2 receptor subtype (GABRA2) and risk for alcohol dependence. The goal of this study was to test whether GABRA2 is associated with alcohol dependence in a sample of Russian alcohol-dependent men. Methods: A total of 113 Russian alcohol-dependent men and 100 male population control subjects were recruited in St. Petersburg and genotyped for seven GABRA2 single-nucleotide polymorphisms (SNPs) using real-time PCR (TaqMan). Six SNPs were located in a GABRA2 haplotype block previously associated with alcohol dependence (AD) in the US population. SNPs and haplotypes were tested for an association to AD using ,2 analysis and a likelihood ratio-based statistic implemented in the software COCAPHASE. Results: Significant associations between two SNPs and AD were observed (p < 0.05). In addition, a trend-level association was observed between AD and three adjacent SNPs (p < 0.1). Associated alleles were carried in a haplotype that was present at frequencies of 0.37 and 0.48 in the control and alcohol-dependent populations, respectively (p < 0.06). Tight linkage disequilibrium spanning from the central portion of the gene to the 3, end was observed in this population. Comparison of the findings to the previously published studies in the US population revealed a highly similar linkage disequilibrium pattern in this population. Conclusions: These findings suggest that genetic variants of GABRA2 increase risk for AD in the Russian population and provide additional support to the hypothesis that polymorphic variation at the GABRA2 locus plays an important role in predisposing to AD at least in European-ancestry populations. [source]

A Proton Magnetic Resonance Spectroscopy Study of Metabolites in the Occipital Lobes in Epilepsy

EPILEPSIA, Issue 4 2003
Robert J. Simister
Summary: ,Purpose: ,-Amino butyric acid (GABA) and glutamate, respectively the principal inhibitory and excitatory neurochemicals in the brain, are visible to proton magnetic resonance spectroscopy (MRS). We report a study of GABA+ (GABA plus homocarnosine) and GLX (glutamate plus glutamine) concentrations in the occipital lobes in patients with idiopathic generalised epilepsy (IGE) and in patients with occipital lobe epilepsy (OLE). Methods: Fifteen patients with IGE, 15 patients with OLE, and 15 healthy volunteers were studied. A single voxel was prescribed in the occipital lobes for each subject. PRESS localised short-echo-time MRS was performed to measure GLX by using LCModel. A double quantum GABA filter was used to measure GABA+. Segmented T1 -weighted images gave the tissue composition of the prescribed voxel. Results: Grey-matter proportion, GLX, and GABA+ were all elevated in IGE. However, analysis using grey-matter proportion as a covariable showed no significant group differences. No correlation was observed between GABA+ concentration and either seizure frequency or time since last seizure. Conclusions: GLX and GABA+ were elevated in IGE. Elevated grey-matter content in the IGE group despite normal MRI appearance can be expected to account for some or all of this observed elevation of GLX and GABA+. GABA+ concentration did not correlate with seizure control or duration since most recent seizure. [source]

GABA and development of the Xenopus optic projection

DEVELOPMENTAL NEUROBIOLOGY, Issue 4 2002
Shane C. D. Ferguson
Abstract In the developing visual system of Xenopus laevis retinal ganglion cell (RGC) axons extend through the brain towards their major target in the midbrain, the optic tectum. Enroute, the axons are guided along their pathway by cues in the environment. In vitro, neurotransmitters have been shown to act chemotropically to influence the trajectory of extending axons and regulate the outgrowth of developing neurites, suggesting that they may act to guide or modulate the growth of axons in vivo. Previous work by Roberts and colleagues (1987) showed that populations of cells within the developing Xenopus diencephalon and midbrain express the neurotransmitter gamma amino butyric acid (GABA). Here we show that Xenopus RGC axons in the midoptic tract grow alongside the GABAergic cells and cross their GABA immunopositive nerve processes. Moreover, RGC axons and growth cones express GABA-A and GABA-B receptors, and GABA and the GABA-B receptor agonist baclofen both stimulate RGC neurite outgrowth in culture. Finally, the GABA-B receptor antagonist CGP54626 applied to the developing optic projection in vivo causes a dose-dependent shortening of the optic projection. These data indicate that GABA may act in vivo to stimulate the outgrowth of Xenopus RGC axons along the optic tract. © 2002 Wiley Periodicals, Inc. J Neurobiol 51: 272,284, 2002 [source]

Glutamatergic neurons are present in the rat ventral tegmental area

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2007
Tsuyoshi Yamaguchi
Abstract The ventral tegmental area (VTA) is thought to play an important role in reward function. Two populations of neurons, containing either dopamine (DA) or ,-amino butyric acid (GABA), have been extensively characterized in this area. However, recent electrophysiological studies are consistent with the notion that neurons that utilize neurotransmitters other than DA or GABA are likely to be present in the VTA. Given the pronounced phenotypic diversity of neurons in this region, we have proposed that additional cell types, such as those that express the neurotransmitter glutamate may also be present in this area. Thus, by using in situ hybridization histochemistry we investigated whether transcripts encoded by genes for the two vesicular glutamate transporters, VGluT1 or VGluT2, were expressed in the VTA. We found that VGluT2 mRNA but not VGluT1 mRNA is expressed in the VTA. Neurons expressing VGluT2 mRNA were differentially distributed throughout the rostro-caudal and medio-lateral aspects of the VTA, with the highest concentration detected in rostro-medial areas. Phenotypic characterization with double in situ hybridization of these neurons indicated that they rarely co,expressed mRNAs for tyrosine hydroxylase (TH, marker for DAergic neurons) or glutamic acid decarboxylase (GAD, marker for GABAergic neurons). Based on the results described here, we concluded that the VTA contains glutamatergic neurons that in their vast majority are clearly non-DAergic and non-GABAergic. [source]

GABA selectively controls the secretory activity of oxytocin neurons in the rat supraoptic nucleus

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2004
Mario Engelmann
Abstract Recently we reported that a single social defeat experience triggers the release of oxytocin (OXT) from somata and dendrites, but not axon terminals, of neurons of the hypothalamic,neurohypophysial system. To further investigate the regulatory mechanisms underlying this dissociated release, we exposed male Wistar rats to a 30-min social defeat and monitored release of the inhibitory amino acids gamma amino butyric acid (GABA) and taurine within the hypothalamic supraoptic nucleus (SON) using microdialysis. Social defeat caused a significant increase in the release of both GABA and taurine within the SON (up to 480%; P < 0.01 vs. prestress release). To reveal the physiological significance of centrally released GABA, the specific GABAA -receptor antagonist bicuculline (0.02 mm) was administered into the SON via retrodialysis. This approach caused a significant increase in the release of OXT both within the SON and into the blood under basal conditions and during stress (up to 300 and 200%, respectively; P < 0.05 vs. basal values), without affecting plasma vasopressin. Electrophysiological studies confirmed the selective action of bicuculline on the firing activity of OXT neurons in the SON. Taken together, our data demonstrate that GABA is released within the SON during emotional stress to act as a selective inhibitor of both central and peripheral OXT secretion. [source]

Taurine selectively modulates the secretory activity of vasopressin neurons in conscious rats

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2001
Mario Engelmann
Abstract Previous experiments have shown that a 10-min forced swimming session triggers the release of vasopressin from somata and dendrites, but not axon terminals, of neurons of the hypothalamic,neurohypophysial system. To further investigate regulatory mechanisms underlying this dissociated release, we forced male Wistar rats to swim in warm (20 °C) water and monitored release of the potentially inhibitory amino acids gamma amino butyric acid (GABA) and taurine into the hypothalamic supraoptic nucleus using microdialysis. Forced swimming caused a significant increase in the release of taurine (up to 350%; P < 0.05 vs. prestress release), but not GABA. To reveal the physiological significance of centrally released taurine, the specific taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide was administered into the supraoptic nucleus via retrodialysis. Administration of this antagonist caused a significant increase in the release of vasopressin within the supraoptic nucleus and into the blood both under basal conditions and during stress (up to 800%; P < 0.05 vs. basal values), without affecting hypothalamic or plasma oxytocin. Local administration of the GABAA receptor antagonist bicuculline, in contrast, failed to influence vasopressin secretion at either time point. In a separate series of in vivo electrophysiological experiments, administration of the same dosage of the taurine antagonist into the supraoptic nucleus via microdialysis resulted in an increased electrical activity of identified vasopressinergic, but not oxytocinergic, neurons. Taken together our data demonstrate that taurine is released within the supraoptic nucleus during physical/emotional stress. Furthermore, at the level of the supraoptic nucleus, taurine inhibits not only the electrical activity of vasopressin neurons but also acts as an inhibitor of both central and peripheral vasopressin secretion during different physiological states. [source]

Effects of six antihypertensive drugs on blood pressure and hypothalamic GABA content in spontaneously hypertensive rats

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2001
Ying Guan
In order to investigate the effects of antihypertensive drugs on blood pressure and ,-amino butyric acid (GABA) content in the hypothalamus and the possible relationship between blood pressure decrease and GABA content changes, blood pressure and GABA contents after chronic (20 weeks) treatments of nitrendipine, atenolol, captopril, hydrochlorothiazide, dihydralazine and prazosin were studied in spontaneously-hypertensive rats (SHR). The acute and subacute (1 week) effects of nitrendipine on GABA contents was also observed in SHR. It was found that 20 week treatments with six different antihypertensive agents produced a decrease in systolic blood pressure and an increase in GABA content. The blood pressure level was significantly correlated with GABA content in the hypothalamus, but not with that in the cortex. Acute treatment with a single dose of nitrendipine, did not alter GABA content. Bicuculline, a GABA receptor antagonist, did not attenuate the hypotensive effect of nitrendipine. In conclusion, chronic treatments by different antihypertensive agents produced an increase of hypothalamic GABA content and a decrease of blood pressure. The increase of GABA content induced by nitrendipine seems likely to be secondary to blood pressure decrease. [source]

Radiosynthesis of novel 18F-labelled derivatives of indiplon as potential GABAA receptor imaging tracers for PET

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 3 2008
Steffen Fischer
Abstract The involvement of gamma amino butyric acid (GABA) receptors in a variety of neurological and psychiatric diseases has promoted the development and use of radiolabelled benzodiazepines (BZ) for brain imaging by PET. However, these radioligands are unable to distinguish between the various subtypes of GABAA receptors. Novel non-BZ such as the pyrazolo-pyrimidine indiplon proved to be selective for the ,1 -subunit of the GABAA receptor. Here, we describe the syntheses of four novel 18F-labelled indiplon derivatives. Radiosyntheses were performed via n.c.a. 18F-nucleophilic substitution starting from the tosyl, bromo, and 4-nitrobenzoyl precursors to obtain fluorine substituted N -alkylamide side chain derivatives of indiplon, followed by multistep purification using semi-preparative high-performance liquid chromatography and solid phase extraction. Tosyl and bromo precursors were converted into 18F-labelled indiplon derivatives with good and reproducible radiochemical yield (RCY) (35,70%, decay corrected), high radiochemical purity (,98.5%), and high specific activity (,>,150,GBq/µmol). By contrast, a low RCY (5,10%) and specific activity (10,15,GBq/µmol) were achieved for the 4-nitrobenzoyl precursor. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Altered gene expression in frontal cortex and midbrain of 3,4-methylenedioxymethamphetamine (MDMA) treated mice: Differential regulation of GABA transporter subtypes

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003
Weiping Peng
Abstract Changes in gene expression were examined in the brain of mice treated with a drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, also called Ecstasy). Frontal cortex and midbrain mRNA, analyzed by differential display polymerase chain reaction (DD-PCR) method, showed an altered expression of several cDNAs, 11 of which were isolated, cloned and sequenced. The sequence of one MDMA-induced mRNA corresponds (99.3%) to the mouse ,-amino butyric acid (GABA) transporter 1 (mGAT1). The established involvement of GABA neurotransmission in the activity of several abused drugs prompted us to focus herein on MDMA effect on the GABA transporter gene family. Semi-quantitative PCR analysis with primers selective to the reported mGAT1 sequence confirmed that MDMA treatment increased mGAT1 expression. Time-course study of the expression of the three GABA transporter subtypes showed that MDMA induced a differential temporal activation of mGAT1 and mGAT4, but had no effect on mGAT2. Quantitative real-time PCR further proved the increased expression of mGAT1 and mGAT4 upon MDMA treatment. Western immunoblotting with anti-GAT1 antibodies showed that MDMA also increased GAT1 protein levels, suggesting that neurotransmission of GABA was altered. MDMA effect was also verified in serotonin transporter knockout (,/,) mice that are insensitive behaviorally to MDMA; the drug did not increase GAT1 protein level in these mutants. In mice, tiagabine and NO-711, inhibitors of GABA transporters, restrained MDMA-induced acute toxicity and death. These results should facilitate novel approaches to prevent deleterious effects, including fatality, induced by MDMA and similar abused psychostimulants. © 2003 Wiley-Liss, Inc. [source]

Association Between Alcoholism and ,-Amino Butyric Acid ,2 Receptor Subtype in a Russian Population

, -Amino Butyric Acid Control of Arginine Vasopressin Release from the Ewe Hypothalamus In Vitro: Sensitivity to Oestradiol

REPRODUCTION IN DOMESTIC ANIMALS, Issue 5 2007
SPS Ghuman
Contents The present study aims to ascertain the influence of , -amino butyric acid (GABA)A or B receptors on arginine vasopressin (AVP) release in vitro and determine whether E2 modulates GABA,AVP interaction. Within 10 min of ewe killing, saggital midline hypothalamic slices (from the anterior preoptic area to the mediobasal hypothalamus along with the median eminence, 2-mm thick, two per ewe) were dissected, placed in oxygenated minimum essential media (MEM)- , at 4°C and within 2 h were singly perifused at 37°C with oxygenated MEM- , (pH 7.4; flow rate 0.15 ml/min), either with or without E2 (24 pg/ml). After 4-h equilibration, 10-min fractions were collected for 4 h interposed with a 10-min exposure at 60 min to a specific GABAA or B receptor agonist or antagonist at various doses (0.1,10 mm). GABAA (muscimol; no E2, n = 7 perifusion chambers, with E2, n = 11) or GABAB (baclofen; no E2, n = 8, with E2, n = 15) agonists (10 mm) did not influence AVP concentrations. However, AVP release increased (p < 0.05) 20,30 min after exposure to 10 mm GABAA or B antagonists (bicuculline, no E2, n = 7: from 4.6 ± 0.7 to 33.0 ± 0.4, with E2, n = 17: from 11.9 ± 1.4 to 32.8 ± 6.0; CGP52432, with E2, n = 14: from 14.0 ± 2.6 to 28.8 ± 3.9 pg/ml). At the end of the collection period, hypothalamic slices responded to KCl (100 mm) with AVP efflux (p < 0.05). GABAB but not GABAA antagonist-stimulated AVP release was enhanced in the presence of E2. In summary, AVP release is under the inhibitory influence of GABA input with further potentiation by E2 through GABAB receptors in vitro. [source]

Comparison of the ultrastructure of cortical and retinal terminals in the rat superior colliculus

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 8 2006
Kamran Boka
Abstract We compared the ultrastructure and synaptic targets of terminals of cortical or retinal origin in the stratum griseum superficiale and stratum opticum of the rat superior colliculus. Following injections of biotinylated dextran amine into cortical area 17, corticotectal axons were labeled by anterograde transport. Corticotectal axons were of relatively small caliber with infrequent small varicosities. At the ultrastructural level, corticotectal terminals were observed to be small profiles (0.44 ± 0.27 ,m2) that contained densely packed round vesicles. In tissue stained for gamma amino butyric acid (GABA) using postembedding immunocytochemical techniques, corticotectal terminals were found to contact small (0.51 ± 0.69 ,m2) non-GABAergic dendrites and spines (93%) and a few small GABAergic dendrites (7%). In the same tissue, retinotectal terminals, identified by their distinctive pale mitochondria, were observed to be larger than corticotectal terminals (3.34 ± 1.79 ,m2). In comparison to corticotectal terminals, retinotectal terminals contacted larger (1.59 ± 1.70 ,m2) non-GABAergic dendrites and spines (73%) and a larger proportion of GABAergic profiles (27%) of relatively large size (2.17 ± 1.49 ,m2), most of which were vesicle-filled (71%). Our results suggest that cortical and retinal terminals target different dendritic compartments within the neuropil of the superficial layers of the superior colliculus. Anat Rec Part A, 288A:850,858, 2006. © 2006 Wiley-Liss, Inc. [source]

Tiagabine in treatment refractory bipolar disorder: a clinical case series

BIPOLAR DISORDERS, Issue 5 2002
Trisha Suppes
Objectives:, Anticonvulsants have provided major treatment advances for patients with bipolar disorder. Many of these drugs, including several with proven efficacy in bipolar mania or depression, enhance the activity of the ,-amino butyric acid (GABA) neurotransmitter system. A new anticonvulsant, tiagabine, has selective GABAergic activity and is approved for patients with partial epilepsy. Few reports of its potential effectiveness in bipolar disorder, however, have been published. We sought to evaluate the effectiveness of tiagabine added to ongoing medication regimens in patients with bipolar disorder inadequately responsive to or intolerant of usual treatments. Methods:, Seventeen treatment-refractory patients participating in the Stanley Foundation Bipolar Network (SFBN) long-term follow-up study were offered open treatment with add-on tiagabine after discussion of the risks, benefits, other treatment options and giving informed consent. Patients' clinical symptoms and somatic complaints were closely monitored with SFBN longitudinal and cross-sectional ratings. Four patients discontinued low-dose tiagabine prior to the second visit and were excluded from data analysis. Results:, Thirteen patients received a mean of 38 days of treatment at a mean dose of 8.7 mg/day of tiagabine. On the Clinical Global Impression Scale for Bipolar Disorder Overall category, three (23%) patients showed much or very much improvement and 10 (77%) patients showed no change or worsening. Three significant adverse events were noted, including two presumptive seizures. Conclusions:, Open add-on tiagabine for treatment-refractory patients with bipolar disorder demonstrated limited efficacy with the majority of patients showing no change or worsening of clinical symptoms. In addition, patients experienced serious side-effects attributed as likely due to the medication, which resolved without lasting consequence when tiagabine was discontinued. [source]

Antiepileptic drug discovery: lessons from the past and future challenges

ACTA NEUROLOGICA SCANDINAVICA, Issue 2005
H. Klitgaard
Historically, most antiepileptic drugs (AEDs) have been discovered either by serendipity, or the screening of compounds using acute seizure models. However, an increasing understanding of the molecular mechanisms underlying epileptogenesis has led to more rational approaches to drug discovery, which have focused on either enhancing inhibitory , -amino butyric acid (GABA)-ergic, or antagonizing excitatory glutamatergic, neurotransmission. Unfortunately, AEDs generated using such strategies have poor efficacy and safety profiles, as they interfere with normal cell processes, while ignoring the complex underlying pathophysiology of epilepsy. Recently, however, the use of new epilepsy models has led to the discovery of levetiracetam, an AED with a truly unique mechanism of action, devoid of anticonvulsant activity in normal animals, but with potent seizure suppression in genetic and kindled chronic epilepsy models, and an unusually high safety margin. The recent identification of brivaracetam and seletracetam, which optimize this unique mechanism of action, may further improve the medical management of epilepsy. The experience with levetiracetam, brivaracetam and seletracetam reveals that new experimental epilepsy models can detect AEDs possessing a unique mechanism of action and thereby target the future challenge of providing clinicians novel additions to the current armamentarium of AEDs. [source]