Research Progress of GABA Receptors in Alzheimer’s Disease / 中国生物化学与分子生物学报

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.

Systematic Effect of Modified Renshen Wumeitang in Regulation of GABA Signaling Pathway in Rats with Diarrhea / 中国实验方剂学杂志

ObjectiveTo investigate the effect of modified Renshen Wumeitang（MRWT） on the related regulatory factors of the γ-aminobutyric acid （GABA） signaling pathway in colon tissues of rats with diarrhea， and reveal the mechanism of MRWT in invigorating Qi， generating fluid， and checking diarrhea. MethodForty-eight SD immature rats were randomly divided into a blank group （n=12） and an experimental group （n=36）. The diarrhea model was induced in the experimental group by Sennae Folium combined with overstrain and improper diet for 14 days. Subsequently， the model rats were randomly divided into a model group （normal saline， 20 mL·kg-1）， a western medicine group （Medilac-Vita， 0.7 g·kg-1）， and a Chinese medicine group （MRWT， 35 g·kg-1）， with 12 rats in each group. The rats in the blank group received normal saline at 20 mL·kg-1， and those in the other groups were treated correspondingly， once a day for 7 days. The general condition， loose stool rate， and diarrhea index of the rats were observed daily. Immunohistochemistry was used to detect the optical density expression of GABA protein in the colon of rats. The content of phosphatidylinositol-3 kinase （PI3K）， protein kinase B2 （Akt2）， phosphorylated Akt （p-Akt）， and interleukin-1β （IL-1β） was determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of PI3K， Akt2， and GABA type A receptor subunit β2 （GABRB2） in the colon of rats were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the blank group， the model group showed worsened general condition， The difference was not statistically significant of loose stool rate and diarrhea index， increased expression of GABA protein （P<0.05）， elevated expression of PI3K， Akt2， p-Akt， and IL-1β （P<0.05， P<0.01）， and up-regulated PI3K， Akt2， and GABRB2 mRNA and protein expression （P<0.01）. Compared with the model group， the western medicine group and the Chinese medicine group showed the improved general condition， decreased loose stool rate and diarrhea index （P<0.01）， and decreased content of PI3K， Akt2， p-Akt， and IL-1β （P<0.05）. The Chinese medicine group displayed decreased mRNA expression of PI3K， Akt2， and GABRB2 （P<0.05， P<0.01） and down-regulated protein expression of GABA， PI3K， and GABRB2 （P<0.05， P<0.01）. The western medicine group exhibited down-regulated mRNA expression of PI3K，Akt2，and protein of PI3K （P<0.05）. ConclusionMRWT can regulate the GABA signaling pathway， reduce Cl- flow in intestinal epithelial cells to the intestinal lumen， and improve the imbalance of colonic fluid metabolism in the colon of diarrhea rats， thereby exerting its effects of invigorating qi， generating fluid， and checking diarrhea.

Association analysis of single nucleotide polymorphisms in the promoter region of GAD1 and GABRB3 with schizophrenia in Chinese Han population / 上海交通大学学报（医学版）

Objective: To investigate the correlation between the polymorphisms of locus in the promoter region of glutamate decarboxylase 1 (GAD1) gene and γ-aminobutyric acid (GABA)A receptor β-3 gene (GABRB3) and schizophrenia (SZ) in Chinese Han population. Methods: SNaPshot genotyping technique was used to detect the polymorphisms of rs3791878 and rs3749034 in the promoter region of GAD1 and rs4906902 in the promoter region of GABRB3 in 545 SZ patients (case group) and 624 healthy controls (control group). The distribution of alleles and genotypes under different genetic models between the case group and the control group in all samples were compared by SNPstats online software. The above analysis was also performed after the subjects were stratified according to gender. The correlation of G/T risk genotype of rs3791878 with the age of the first onset of male SZ was investigated by survival analysis. Results: Under over-dominant genetic model, the distribution of G/T risk genotype of rs3791878 showed statistically difference between the male SZ cases and male controls (P=0.000), and the difference was still statistically significant after Bonferroni correction (P=0.000). However, there was no significant difference in the distribution of alleles and genotypes under different genetic models of rs3749034 and rs4906902 between the case group and the control group in all samples (P>0.05), and there was also no significant difference in the distribution of alleles between the case group and the control group after them being stratified according to gender (P>0.05). Kaplan-Meier analysis showed that there was no significant difference between the age of onset of male SZ who carried G/T genotype in rs3791878 locus and that of male SZ who did not carry it (P=0.603). Conclusion: The polymorphism of rs3791878 in the promoter region of GAD1 is significantly associated with the incidence of male SZ in Chinese Han population.

Anxiolytic Effect of Chanmu Anshen Granule and Its Bioactive Mechanism / 中国实验方剂学杂志

Objective:To assess the anxiolytic effect of Chaimu Anshen granules (CMASG) and investigate its bioactive mechanism. Method:ICR mice were randomly divided into normal group, diazepam group(0.002 g·kg-1),Jieyu Anshen granules group(0.001 4 g·kg-1), high, medium, and low-dose (0.001 98,0.000 99,0.000 495 g·kg-1)Chaimu Anshen granule groups, with 20 mice in each group. To detect the anxiolytic effect of CMASG, mice were intragastrically administered for 4 weeks in the morning, and light-dark box transition test and open field test were performed once the other day. After the behavior tests, blood samples were collected. Six mice of each group were perfused with formalin through heart, and then the brains were fixed for immunohistochemistry test. Hippocampus of the other mice in each group were collected and stored in liquid nitrogen. The content of γ-aminobutyric acid(GABA)and glutamic acid(Glu)in hippocampus and blood samples were detected by enzyme-linked immunosorbent assay (ELISA), and the ratio of GABA/Glu was calculated. The expression of GABAα1 receptor was evaluated by the immunohistochemistry method. To test the hypnosis effect of CMASG, mice were administered intragastrically for 7 days. The sub-threshold dose of pentobarbital sodium in the sleep experiment was tested. Result:Compared with normal group, the light-dark box transitions test demonstrated that low-dose and medium-dose CMASG groups significantly prolonged the duration in light box(PPPPPPPPPPα1 receptor protein in hippocampus showed that the medium-dose CMASG significantly increased the expression of GABAα1 protein. The sub-threshold dose of pentobarbital sodium on sleep experiments confirmed that the medium-dose CMASG significantly increased the rate of sleep in mice. Conclusion:CMASG showed an anxiolytic effect, and its bioactive mechanism was related with the increase of GABA content, and the decrease of Glu content in hippocampus. Furthermore, it increased the expression of GABAα1 protein in hippocampus. The changes in content of GABA and Glu in peripheral blood were positively correlated with the changes in hippocampal tissues, which provided reference for clinical diagnosis. CMASG also exhibited an effect in improvement of sleep.

Potentiation of decursinol angelate on pentobarbital-induced sleeping behaviors via the activation of GABA(A)-ergic systems in rodents

Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of GABA(A)-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and 0.1 µg/ml) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase (GAD(65/67)) and GABA(A) receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of GABA(A)-ergic systems, and can be useful in the treatment of insomnia.

Neuroprotective effects and mechanisms of Cerebroprotein Hydrolysate for Injection (Ⅰ) on vascular dementia in rats / 药物评价研究

Objective To investigate the neuroprotective mechanisms of Cerebroprotein Hydrolysate for Injection (Ⅰ) on vascular dementia in rats.Method The rat vascular dementia model was prepared using an improved two-vessel occlusion method,and the common carotid artery was only isolated but not blocked in sham group.Rats were randomly divided into sham group,model group,Cerebroprotein Hydrolysate for Injection (Ⅰ) groups with low,medium and high dose (5,10,20 mg/kg) and Cerebroprotein Hydrolysate Injection group (Cerebrolysin,Positive drug,10 mg/kg).The drug was administered by iv injection of rat tail vein once a day for two weeks,while the same volume of saline was administered in sham and model group.At the end of administration,the plasma was collected through abdominal aorta to separate serum,and rat cortex was isolated to prepare homogenate.The levels of nerve growth factor (NGF) and insulin-like growth factor 2 (IGF-2) in serum and level of gamma-aminobutyric acid (GABA) in cortex were detected by ELISA.Level of glutamate (Glu) in cortex of VaD rats was detected by colorimetry.Results Compared with model group,levels of NGF and IGF-2 in the serum of VaD rats and level of GABA in cortex were significantly increased,while level of Glu in cortex was significantly decreased after administration of Cerebroprotein Hydrolysate for Injection (Ⅰ).The increased IGF-2 and GABA levels by Cerebroprotein Hydrolysate for Injection (Ⅰ) were significantly higher than that of Cerebrolysin at same dose.Conclusion The mechanisms underlying the increased leaming and memory ability of VaD rats by Cerebroprotein Hydrolysate for Injection (Ⅰ),are possibly related to the increased levels of NGF and IGF-2 in body and a regulation of the balance between excitatory and inhibitory amino acid neurotransmitters.

Neuroprotective effects and mechanisms of Cerebroprotein Hydrolysate for Injection (Ⅰ) on vascular dementia in rats / 药物评价研究

Objective To investigate the neuroprotective mechanisms of Cerebroprotein Hydrolysate for Injection (Ⅰ) on vascular dementia in rats.Method The rat vascular dementia model was prepared using an improved two-vessel occlusion method,and the common carotid artery was only isolated but not blocked in sham group.Rats were randomly divided into sham group,model group,Cerebroprotein Hydrolysate for Injection (Ⅰ) groups with low,medium and high dose (5,10,20 mg/kg) and Cerebroprotein Hydrolysate Injection group (Cerebrolysin,Positive drug,10 mg/kg).The drug was administered by iv injection of rat tail vein once a day for two weeks,while the same volume of saline was administered in sham and model group.At the end of administration,the plasma was collected through abdominal aorta to separate serum,and rat cortex was isolated to prepare homogenate.The levels of nerve growth factor (NGF) and insulin-like growth factor 2 (IGF-2) in serum and level of gamma-aminobutyric acid (GABA) in cortex were detected by ELISA.Level of glutamate (Glu) in cortex of VaD rats was detected by colorimetry.Results Compared with model group,levels of NGF and IGF-2 in the serum of VaD rats and level of GABA in cortex were significantly increased,while level of Glu in cortex was significantly decreased after administration of Cerebroprotein Hydrolysate for Injection (Ⅰ).The increased IGF-2 and GABA levels by Cerebroprotein Hydrolysate for Injection (Ⅰ) were significantly higher than that of Cerebrolysin at same dose.Conclusion The mechanisms underlying the increased leaming and memory ability of VaD rats by Cerebroprotein Hydrolysate for Injection (Ⅰ),are possibly related to the increased levels of NGF and IGF-2 in body and a regulation of the balance between excitatory and inhibitory amino acid neurotransmitters.

Study on the Influence of Needling the Eight Confluent Points plus Huo Xue Rong Luo Granules on GABA and Gly in ;Patients with Spastic Paralysis After Cerebral Infarction / 上海针灸杂志

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).

Effects of N-acyl glucosamines on GABA uptake activity of GABA transporter 1 / 中国药科大学学报

@#In order to screen the inhibitors of GAT1 protein, the effects of synthetic N-acylglucosamines on the GABA uptake activity of GAT1 were examined in the HEK-293 cell model stably expressing GAT1 by performing GABA uptake assay. And since the N-linked oligosaccharides, especially their terminal sialic acid of GAT1 are necessary for the function of GAT1, their effects on the modification of N-glycans of GAT1 were also determined by the quantitative analysis of the sialic acid of GAT1. The results showed that 10 mmol /L 3-O-methyl-N-acetylglucosamine(3-O-Met-GlcNAc)reduced the GABA uptake activity of GAT1 to 53%(P< 0. 01)through inhibiting the sialylation of GAT1(66. 8%). And the GABA uptake activities were decreased to 54%, 63%, 63% and 67%(P< 0. 01), respectively, by the treatments of 10 mmol /L N-propionylglucosamine(GlcNProp), N-hexanoylglucosamine(GlcNHex), N-cycloproylgormylglucosamine(GlcNCyclo)and N-acetamidoacetylglucosamine(GlcNAc-acetamido)through inhibiting N-glycan trimming. These results indicate that the analogues of glucosamines have great potential in the development of inhibitors of GAT1 activity or sialic acid biosynthesis.

The enhancement of GABAA-mediated currents by sufentanil in isolated dorsal root ganglion neurons in rats / 实用医学杂志

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.

Identification of a Novel GABAA Receptor Channel Ligand Derived from Melissa officinalis and Lavandula angustifolia Essential Oils.

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.

Submerged fermentation of Lactobacillus rhamnosus YS9 for γ aminobutyric acid (GABA) production

γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in central nervous system, and its application in drugs and functional foods has attracted great attention. To enhance production of y-aminobutyric acid, Lactobacillus rhamnosus YS9, a strain isolated from Chinese traditional fermented food pickled vegetable, was grown under submerged fermentation. Its cultivation conditions were investigated. When culture pH condition was adjusted to the optimal pH of glutamate decarboxylase activity, culture of Lb. rhamnosus YS9 in medium supplemented with 200 mM of monosodium glutamate and 200 µM of pyridoxal phosphate (PLP), produced 187 mM of GABA.

Effects of poly-gamma-glutamic acid on serum and brain concentrations of glutamate and GABA in diet-induced obese rats

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.

Association between γ-Aminobutyric Acid B2 Receptor Gene Polymorphism rs3750344 and Bone Mass Content or Bone Mass Density in Chinese Hans Population / 中国康复理论与实践

@# ObjectiveTo investigate the association of γ-aminobutyric acid B2 receptor (GABABR2) gene polymorphism rs3750344 and bone mass (bone mass content, BMC, and bone mass density, BMD) in population of Chinese Hans lives in Jinan. Methods425 volunteers were recruited. BMC and BMD of all subjects were measured with dual energy X-ray absorptiometry (DXA). Genotyping of polymorphism rs3750344 was conducted using Taqman assays. ResultsBMD and BMC increased with the copy of the C allele of rs3750344 in whole body. ConclusionThe C allele of GABABR2 rs3750344 increases the levers of BMD and BMC in Chinese Han population.

Single Nucleotide Polymorphisms of GABRG2 in Idiopathic Generalized Epilepsies(IGEs) / 대한소아신경학회지

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.

RAPID DETERMINATION OF GLUTAMATE DECARBOXYLASE ACTIVITY FROM LACTIC ACID BACTERIA BY SPECTROMETRIC METHOD AND ITS APPLICATIONS / 微生物学通报

In this paper, a colorimetric method with high sensitivity, reproducibility and low cost for determining glutamate decarboxylase (GAD) activity was developed based on Berthelot reaction. The optimum substrate system is 0.2 mol/L MacIlvaine buffer pH4.7, containing 0.1 mmol/L pyridoxal phosphate (PLP) and 10 mmol/L L-monosodium glutamate (L-MSG). The reaction mixture consisted of 200 ?L substrate solution and 1～100 ?L enzyme preparation from lactic acid bacteria and was incubated at 30℃. The enzymatic reaction was terminated by immersion in ice-water and addition of 200 ?L 0.2 mol/L sodium borate buffer, pH9.0, then 1 mL 6% phenol solution and 400 ?L sodium hypochloride were added. Color development was carried out in boiling water for 10 min then immediately put in ice-water bath for 20 min. The optical density is read at 630 nm. ?-aminobutyric acid (GABA) produced was calculated using the standard curve. Applications of the method in GAD studies were discussed.

LOCALIZATION OF GABAB RECEPTOR 1 SUBTYPE IN THE RAT NERVOUS SYSTEM / 解剖学报

Objective To observe the distribution of GABAB receptor subtype 1 (GABABR1 ) in the rat nervous system. Method Immunocytochemical staining technique by using specific antibody against GABABR1 was used. Results Intensely and densely stained GABABR1-like immunoreactive neurons were observed in the V layer of cerebral cortex. islands of Calleja, caudate putamen, septohippocampal nucleus, hippocampus, basolateral amygdaloid nucleus, medial habenular nucleus, anterodorsal thalamic nucleus, mediodorsal thalamic nucleus, dorsal lateral geniculate nucleus. preoptic nuclei, supraoptic nucleus, lateral magnocellular part of paraven- tricular nucleus, anterior commisural nucleus, median eminence, arcuate nucleus, pars compacta of substantia nigra, ventral tegmental area, interpeduncular nucleus, Edinger-Westphal nucleus, mesencephalic trigeminal nucleus, locus coeruleus, nucleus of the trapezoid they, superficial layers of the caudalis subnucleus of the spinal trigeminal nucleus, dorsal motor nucleus of vagus, Purkinje cell layer of cerebellar cortex, laminae Ⅰ- Ⅲ, Ⅸ and X of spinal gray matter, lateral spinal nucleus, Onuf's nucleus and spinal dorsal root ganglion. Specially, in the cholinergic and monoaminergic nuclei of the brain. Conclusion These results indicate that GABABR1-like im- munoreactive structures are widely located in the rat brain. GABA might exert its principal inhibitory effects through these GABABR.

Neuroprotective effect of sodium oxybate against focal cerebral ischemia-reperfusion injury and the relation to GABA in rats / 中国药理学通报

AIMTo study the protective effect of sodium oxybate (SO) against focal cerebral ischemia-reperfusion injury in rats, and the relationship between the effects of SO and ?-aminobutyric acid (GABA). METHODSThe reversible middle cerebral artery occlusion (MCAO)model in rats was established to investigate the role of SO. The scores of neurological deficits was detected by Longa EZ method in MCAO rats. The extracellular levels of glutamate (Glu) and GABA in CSF were measured by high performance liquid chromatography-fluorometer (HPLC-FR) method, and the weight of cerebral infraction was detected. RESULTSThe scores of neurological deficits and the weight of cerebral infraction markedly decreased by SO while the ratio of GABA/Glu obviously increased administered SO in MCAO rats. CONCLUSIONSSO could prevent MCAO rats from ischemia-reperfusion injury, the protective effect is related to SO keeping dynamic balance of excition-inhibition, and persisting inhibition-depended effect.