ABSTRACT
Alzheimer’s disease (AD) is a progressive neurodegenerative disease with the early symptom of A β plaque, tau hyperphosphorylation neuronal tangle formation in cells. At present, accumulated evidence shows that the changes of GABA receptors are closely related to AD. Some studies have shown that the expression level of each subunit of the GABA receptor changes in AD patients. Therefore, it is speculated that the changes of GABA subunits may be related to the pathogenesis of AD, but there is no better methods to improve AD by targeting GABA receptors. In order to further understand the relationship between the changes of GABA receptors and AD, this paper first reviewed the changes of GABA receptors in AD patients and animal models’ brains and found that there was differential expression in GABA(A) receptor subunits in AD patients. Then we summarized the changes of GABA receptor subunits in Alzheimer database. Based on the data, we found that a few GABA subunits had significant changes. The evidence shows that the change of GABA receptors alters the neural activity in the brain. Other studies have found that the treatment of mice with GABA receptor agonists and antagonists can improve the cognitive ability of mice. We hope that understanding the differential expression of GABA receptors in AD will provide a more accurate target for the treatment of AD.
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Objective To observe the influence of needling the Eight Confluent Points plus Huo Xue Rong Luo granules on the levels of gamma-aminobutyric acid (GABA) and glycine (Gly) in patients with spastic paralysis after cerebral infarction. Method Sixty patients with spastic paralysis after cerebral infarction were randomized into a treatment group and a control group, 3 0 cases each. The control group was intervened by basic treatment, while the treatment group was by Huo Xue Rong Luo granules plus acupuncture at the Eight Confluent Points in addition to the basic treatment, for 6 treatment courses in total. Before the treatment, and after half-a-month, 1-month, and 3-month treatments, the Chinese Stroke Scale (CSS) and activities of daily living (ADL) were evaluated, the levels of GABA and Gly were detected by using high performance liquid chromatography (HPLC), and the therapeutic efficacies were compared. Result After half-a-month treatment, the CSS score dropped significantly in both groups (P0.05). Conclusion Needling the Eight Confluent Points plus Huo Xue Rong Luo granules is effective in treating spastic paralysis after cerebral infarction, which is plausibly associated with the up-regulation of inhibitory neurotransmitters (GABA and Gly).
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Objective To investigate the modulatory effect of different dosage of sufentanil on I GABA in rat dorsal root ganglion neurons. Methods The rat root ganglion neurons were enzymatically dissociated. The whole-cell patch clamp techniquewas applied to record the effect of 0.02 , 0.1, 0.5, 2.5 μmol/L sufentanil and 0.5 mol/L sufentanil + 1 nmol/L Naloxone, a non-specific ityopioid receptor antagonist on IGABA. Results 0.02, 0.1, 0.5, 2.5 μmol/L sufentanil potentiated IGABA to (108.7 ± 6.7)%,(122.0 ± 2.3)%, (146.7 ± 7.9)% and (130.1 ± 5.6)%, respectively (n = 10; *P < 0.05, **P < 0.01). The potentiation role of 0.1,0.5, 2.5 μmol/L sufentanil on IGABA lasted 10 to 20 min The potentiation could be blocked by Naloxone (n = 7; *P < 0.05, **P < 0.01). Conclusion Sufentanil activates μ opioid receptor and potentiates the action of GABAA receptor, and the potentiation could be blocked by Naloxone. The enhancement of currents by sufentanil may increase GABA A receptor-mediated presynaptic inhibition at the spinal cord level.
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Aims: Melissa officinalis (Mo) and Lavandula angustifolia (La) essential oils and their major constituents ((E) - caryophyllene, caryophyllene oxide, geranyl acetate, linalool, nerol, Oct-1-en-3-ol, 3-Octanone, myrcene, allo-ocimene, p-cymene and α- terpineol) assessed by GC-MS) which are shared by these two essential oils were probed in an attempt to identify the GABAAR ligand(s). Study Design: [35S] t-butylbicyclophosphorothionate (TBPS) radioligand binding assay to GABAA receptors. In vitro neuronal viability assay. Place and Duration of Study: School of Biological and Biomedical Sciences, Durham University, United Kingdom (December 2012 and January 2013). Results: One of the major component (s) of (Mo), trans-ocimene, inhibited [35S] (TBPS) binding to native GABAA receptors in a concentration-dependent manner with an apparent IC50 of 40μM. Concentrations (0.001 mg/ml) of whole (Mo) were shown to display modest beneficial effects upon neuronal viability while at a higher concentration (0.1 mg/ml) of (Mo) and (La) oils induced a neurotoxicity effect. Conclusion: These data provide the first evidence that allo-ocimene is an neuroactive GABAA R inhibitory component found in both (Mo) and (La), and represents a novel GABAA receptor channel chemotype derived from a natural product.
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Poly-gamma-glutamic acid (gamma-PGA) is a mucilaginous and biodegradable compound produced by Bacillus subtilis from fermented soybeans, and is found in the traditional Korean soy product, cheongkukjang. This study was carried out to evaluate the effects of gamma-PGA from a food source on the concentration of the neurotransmitter GABA and its metabolic precursor glutamate in diet-induced obese rats. Eight-week old male Sprague-Dawley rats (n=60) were used. The rats were divided into two groups and obesity was induced by providing either a 10% control fat or 45% high fat diet for 5 weeks. The rats were then blocked into 6 groups and supplemented with a 0.1% gamma-PGA diet for 4 weeks. After sacrifice, brain and serum GABA and glutamate concentrations were analyzed by high performance liquid chromatography with fluorometric detection. The rats fed the high fat diet had significantly increased body weights. gamma-PGA supplementation significantly increased serum concentrations of glutamate and GABA in the control fat diet groups while this effect was not found in the high fat groups. In the brain, glutamate concentrations were significantly higher in the gamma-PGA supplemented groups both in rats fed the normal and high fat diets than in the no gamma-PGA controls. GABA concentrations showed the same tendency. The results indicated that gamma-PGA intake increased GABA concentrations in the serum and brain. However, the effects were not shown in obese rats.
Subject(s)
Animals , Humans , Male , Rats , Bacillus subtilis , Body Weight , Brain , Chromatography, Liquid , Diet , Diet, High-Fat , gamma-Aminobutyric Acid , Glutamic Acid , Neurotransmitter Agents , Obesity , Polyglutamic Acid , Rats, Sprague-Dawley , Glycine maxABSTRACT
PURPOSE: Mutations in gamma-aminobutyric acid(GABA) A receptor gamma2 subunit gene (GABRG2) were independently identified in families of generalized epilepsy with febrile seizures plus(GEFS+) and families of absence epilepsy and febrile seizures(FSs). The present study assessed the role of GABRG2 gene in idiopathic generalized epilepsies(IGEs) of Korean population. METHODS: Twenty-three IGEs and 94 healthy control subjects were selected through a collaborative study of Catholic Child Neurology Research Group. The SNP211037 of GABRG2 were screened by DHPLC. DNA fragments showing variant chromatograms were subsequently sequenced. Genotypes and allelic frequencies for GABRG2 gene polymorphism in three groups were compared. RESULTS: Genotypes and allelic frequencies of the gamma2 subunit of the GABA receptor gene(SNP211037) in both groups were not significantly different. The most common genotypes for GABRG2(SNP211037) gene in both groups were T/C heterozygote. The allele C and T frequencies for GABRG2(SNP211037) in the IGEs group were 45.7% and 54.3%, respectively and in healthy control group, 42.6% and 57.4%, respectively. The number of individuals with the GABRG2 (SNP211037)-C/C genotype in the IGEs group was greater compared with that in the healthy control group(21.7% versus 12.8%). The odds ratio for developing IGEs in individuals with the GABRG2 (SNP211037)-CC genotype was 1.65 compared with individuals with the GABRG2 (SNP211037)-T/T genotype, which was not significantly different. CONCLUSION: These data suggest that genomic variations of GABRG2 might not be one of the susceptibility factors for IGEs in the Korean population.