脑内γ-氨基丁酸能神经及其功能

γ-氨基丁酸(GABA)是脊椎动物中枢神经系统中一种主要的抑制性神经介质。脑内1/3的突触以它为递质。它也是三羧酸循环中“GABA环路”的产物,在体内作为供能物质参与能量代谢。作为神经递质的GABA可在神经末梢合成,约占脑内GABA全部含量的25～30%。同其它神经介质相比,脑内GABA的含量是很高的,其浓度以微克分子/克(脑组织)计算。GABA的结构简单,但功能复杂。关于GABA能神经元的分布、功能特性、受体分类以及与安定受体的关系等方面近年来作了大量的研究。一、GABA能神经元近几年由于方法学上的改进,人们对GABA能神经元有了更多的认识。例如,Robert     

西藏来源的植物内生酵母Wickerhamomyces rabaulensis生产γ-氨基丁酸北大核心

【目的】对西藏地区分离的一株植物内生维克汉姆酵母Wickerhamomyces rabaulensis JT229生产γ-氨基丁酸(γ-aminobutyric acid,GABA)的条件进行研究,并考察胁迫处理对生产的影响。【方法】利用26S rDNA序列进行菌株鉴定,考察葡萄糖和木糖对W.rabaulensis JT229生产GABA的影响,并利用添加乙酸、乙醇和高温等胁迫条件提升其发酵生产GABA的能力。【结果】W.rabaulensis JT229可以利用葡萄糖和木糖生产GABA,并且在适当的高温、乙酸和乙醇的胁迫诱导下胞外GABA浓度明显提升,产量分别为80.07、67.02、104.15 mg/L,分别是对照条件下的2.15、1.85和2.87倍,且胞内也检测到存在一定浓度的GABA。在添加5g/L乙酸和37℃高温胁迫的条件下,胞内ROS水平和细胞膜透性均有明显提高;添加3 g/L乙酸的条件与对照组相比,胞内ROS水平有所下降,但是细胞膜透性有明显提升;在37℃的胁迫条件下胞内GABA含量明显下降。胞外的GABA产量提升推测是由于胁迫导致胞内GABA外排增多导致的。【结论】本研究首次在国内外分离鉴定了内生酵母W.rabaulensis,并发现菌株W.rabaulensis JT229具有生产GABA的潜力,此外,利用胁迫处理促进了该菌株的GABA胞外生产,为进一步开发利用酵母资源生产GABA及富含GABA的产品提供了基础。     

中枢疲劳研究与思考

中枢疲劳既可以作为独立疾病影响人们的日常工作和学习,又可以作为症状出现于多种慢性疾病,其定义和机制国内外说法不尽相同。中枢疲劳是由于中枢神经系统发生退行性或其他不良变化,从而导致躯体、神经、包括心理一系列的疲劳样反应。其机制涉及到中枢神经系统和外周传导系统等多个维度、多个节点的变化,充分把握中枢疲劳的概念本质及潜在生物学机制对其临床防治有着重要理论和实践意义。此外,动物模型作为基础研究的前提和必要工具是中枢疲劳研究过程中又一重要问题。本文在文献整理的基础上,先从定义的角度出发由疲劳引申到中枢疲劳,将现阶段对中枢疲劳的不同概念阐述做一分析,并从机制和动物模型两个方面展开对国外研究进展进行综述。     

苍白球γ-氨基丁酸能神经传递及其与神经系统疾病的关系

苍白球是基底神经节间接环路的重要核团,在机体运动功能调节中发挥重要作用。近年来,苍白球在基底神经节正常及异常功能调节中的重要性已日渐受到重视。然而,目前对苍白球内各种神经递质系统的功能活动了解较少。GABA是苍白球主要的神经递质。采用电生理记录、免疫组织化学及行为测试等实验方法,人们对大鼠苍白球GABA能神经传递系统的受体分布及功能活动有了新的认识。形态学研究揭示,苍白球存在GABAA受体及其苯二氮卓结合位点和GABAB受体。在亚细胞水平,GABAA受体主要位于对称性突触(GABA能突触)的突触后膜,而GABAB受体则位于对称性突触和非对称性突触(兴奋性突触)的突触前膜及突触后膜。功能学研究进一步揭示,激活苍白球突触前膜GABAB自身和异源性受体可分别减少GABA和谷氨酸释放;激活突触后膜GABAB受体,可引起苍白球神经元超极化。除GABAB受体外,激活苍白球GABAA受体苯二氮卓结合位点及阻断GABA重摄取可延长GABA电流持续时间,从而改变苍白球神经元兴奋性。与离体实验结果相一致,激活苍向球GABAB受体和苯二氮卓结合位点及阻断GABA重摄取可引起整体动物旋转行为。苍白球GABA神经递质系统与帕金森病病因学及癫痫发病有关。已证实,苍白球神经元放电频率的降低及簇状放电的产生与帕金森病运动减少及静止性震颤等症状直接相关。此外,电牛理及行为学实验发现,新型抗癫痫药物替加平可调节苍白球神经元功能活动．这为进一步了解苍白球与癫痫发病的关系提供了新的理论及实验依据。     

GABA及BZD受体与肝脑病

GABA及BZD受体γ-氨基丁酸(γ-aminobutyric acid,GABA)是中枢神经系统的主要抑制性递质,它的抑制效应是通过兴奋GABA受体而实现的。根据GABA受体对药物的不同选择性,可分为GABA_A和GABA_B两种受体,前者又可进一步分成GABA_(A-1)、GABA_(A-2)及GABA_(A-3)等亚型。自1984年以来,国际上有几家实验室用各种现代技术(如分子生物学、免疫亲和层析等技术)来提取和纯化动物脑内的GABA受体。目前已了解到GABA_A受体是一个四聚体,分别有2个α及2个β亚单位构成。现已能人工合成GABA_A受     

心理疲劳的研究进展

心理疲劳是指重复单一作业或从事紧张程度较大的工作,神经系统紧张程度过高,从而出现的心理不安和疲乏感。心理疲劳会造成个体各种心理疾病以及重大事故的出现,但至今心理疲劳的概念还未有统一的标准,病因病机不明确,本文意在探讨其研究进展。笔者对于心理疲劳的国内外研究进展进行了文献整理,从心理疲劳的定义、表现、病因病机以及检测方法四个方面论述,发现心理疲劳由工作强度与持续时间、心理负荷、工作方法和熟练程度、环境因素以及体质、健康和营养状况等原因引起不同脑区的神经系统的变化以及相应物质代谢产生的疲劳。目前对心理疲劳的研究方法和手段有待改进,可将脑磁图、正电子发射断层扫描技术、功能核磁共振成像技术大量应用到研究中,探索其神经生理机制,为预防和治疗心理疲劳提供思路和方法。     

芽孢杆菌γ-氨基丁酸代谢旁路研究进展

-γ氨基丁酸(γ-aminobutyric acid,GABA)是一种在生物体中普遍存在的四碳非蛋白质氨基酸,具有较为广泛的生理功能。其代谢是通过GABA旁路(GABA shunt)来完成的。现就其基本性质、代谢调控特点、表达调控机制及其生理功能等方面分别介绍芽孢杆菌γ-氨基丁酸代谢旁路的研究进展。系统研究苏云金芽孢杆菌中γ-氨基丁酸代谢旁路的调控机制和生理功能,有可能为进一步了解其杀虫晶体和芽孢的形成机制提供思路和线索。     

γ-氨基丁酸与心血管活动的调节

γ-氨基丁酸(GABA)是脑内具有普遍抑制作用的一种神经介质,它涉及多种重要功能。近年来,不少报道说明GABA与心血管活动调节有密切关系。这方面的研究多采用药理学方法。由于所用药物和用药方法不同,常引致不同的实验结果。一、GABA的中枢作用GABA在中枢有降压作用,也有升压作用。从目前的资料看,GABA降压作用的报道较多。(一)GABA的降压作用1973年,Guertzenstein首先提出GABA作用于脑干,引起血压下降。其后,Antonaccio等报道,向猫脑室注射GABA受体激动剂异鹅羔胺(musci-mol),动物血压明显降低和心率减慢。脑室内注射GABA也得到类似结果。这些药物的     

GABA在中枢神经系统发育的早期阶段具有兴奋作用

在发育早期中枢神经系统γ－氨基丁酸（γ-aminobutyric acid,GABA）主要作为兴奋性神经递质而发挥作用,它可使神经元产生去极化,升高胞内Ca^2 浓度,此时GABA发挥了重要的神经营养性作用,随着兴奋性谷氨酸能系统的发育,通过Cl^-转运体的表达变化,胞内Cl^-浓度降低,从而使GABA由兴奋性转变为抑制性。     

大豆对预防老年痴呆的研究进展

随着人口老龄化问题的加剧,老年痴呆的发病比例逐年上升,并已成为困扰全人类的重大疾病问题。在缺乏明确治疗手段的情况下通过饮食结构调整进行提早预防对于改善现状具有重要意义。大豆是人类饮食中重要的组成部分,因其富含大豆异黄酮、大豆磷脂、γ-氨基丁酸(GABA)等多种对老年痴呆具有改善作用的生物活性物质而备受关注。综述了大豆磷脂、大豆异黄酮及GABA对预防老年痴呆的研究进展,并概述了萌芽在改善大豆营养组分方面的应用,以期为老年痴呆的防治及拓宽大豆在老年痴呆防治上的应用提供理论依据。     

海军指战员心理健康状况研究现状

我国军人的心理健康状况从80年代后期开始有了较为系统的研究。海军指战员是社会的特殊群体,健康的心理素质可以使海军指战员保持战斗力,更好的适应国防现代化的需要。海军指战员在一段较长的时间内,整日面对单一枯燥的环境,承受巨大工作压力,加之其他一些影响因素,难免产生诸多心理问题。因此,探讨职业特殊环境对海军指战员心理健康造成的影响,对海军指战员人格结构及心理健康状况进行评价,用以指导海军官兵在特殊环境中提高心理素质,避免不良影响,最终提高部队战斗力具有十分重要的意义。通过查阅文献了解海军特殊职业环境对士兵心理健康影响的研究现状,总结当前应用的各种评价工具、异常心理状况、影响因素及其危害,分析海军心理健康研究方面存在的不足与亟待解决的问题,为今后的研究提供参考。     

海军指战员心理健康状况研究现状

我国军人的心理健康状况从80年代后期开始有了较为系统的研究。海军指战员是社会的特殊群体,健康的心理素质可以使海军指战员保持战斗力,更好的适应国防现代化的需要。海军指战员在一段较长的时间内,整日面对单一枯燥的环境,承受巨大工作压力,加之其他一些影响因素,难免产生诸多心理问题。因此,探讨职业特殊环境对海军指战员心理健康造成的影响,对海军指战员人格结构及心理健康状况进行评价,用以指导海军官兵在特殊环境中提高心理素质,避免不良影响,最终提高部队战斗力具有十分重要的意义。通过查阅文献了解海军特殊职业环境对士兵心理健康影响的研究现状,总结当前应用的各种评价工具、异常心理状况、影响因素及其危害,分析海军心理健康研究方面存在的不足与亟待解决的问题,为今后的研究提供参考。     

Molecular basis of X-linked non-specific mental retardation

Mental retardation (MR) is a common disorder, affecting 1-3% of the total population. This condition results from failure to develop cognitive abilities and intelligence level appropriate for the age group. Mental retardation is basically a clinically as well as etiologically heterogeneous type of condition and both genetic and non-genetic factors have been found to be involved. There are more than 1000 entries in Online Mendelian Inheritance in Man (OMIM) database under the name of mental retardation. In recent years 15 genes for X linked non-specific mental retardation have been identified which provide important clues regarding molecular and cellular processes involved in signal transduction cascade in central nervous system. Recent advancements in identification and characterization of X-linked non-specific mental retardation genes have been discussed in this review. Understanding of the molecular pathways of disease causing genes would be helpful in developing effective therapeutic approaches for mental retardation.     

gamma-Aminobutyric acid in peripheral tissues

Significant amounts of gamma-aminobutyric acid (GABA), an endogenous amino acid, are present in mammalian peripheral tissues. This finding led to the suggestion that GABA may act as a neurotransmitter in the peripheral nervous system as it does in the central nervous system. This review deals with recent identification of GABA in the autonomic nervous system and the possible functional role of GABA in neuronal and non-neuronal tissues. The identification of GABA in the autonomic nervous system has paved the way for new approaches in pharmacological investigations.     

GABAB receptor association with the PDZ scaffold Mupp1 alters receptor stability and function

gamma-Aminobutyric acid, type B (GABA(B)) receptors are heterodimeric G protein-coupled receptors that mediate slow inhibitory synaptic transmission in the central nervous system. To identify novel interacting partners that might regulate GABA(B) receptor (GABA(B)R) functionality, we screened the GABA(B)R2 carboxyl terminus against a recently created proteomic array of 96 distinct PDZ (PSD-95/Dlg/ZO-1 homology) domains. The screen identified three specific PDZ domains that exhibit interactions with GABA(B)R2: Mupp1 PDZ13, PAPIN PDZ1, and Erbin PDZ. Biochemical analysis confirmed that full-length Mupp1 and PAPIN interact with GABA(B)R2 in cells. Disruption of the GABA(B)R2 interaction with PDZ scaffolds by a point mutation to the carboxyl terminus of the receptor dramatically decreased receptor stability and attenuated the duration of GABA(B) receptor signaling. The effects of mutating the GABA(B)R2 carboxyl terminus on receptor stability and signaling were mimicked by small interference RNA knockdown of endogenous Mupp1. These findings reveal that GABA(B) receptor stability and signaling can be modulated via GABA(B)R2 interactions with the PDZ scaffold protein Mupp1, which may contribute to cell-specific regulation of GABA(B) receptors in the central nervous system.     

Ethanol and GABA

A study of the literature showed that the GABA system is an important target of ethanol in the central nervous system, in part as a consequence of damage in membrane-bound enzymes and receptors. A single dose of ethanol initially activates the GABA system which is weakened after chronic administration because of overcompensation. Interest is focused on the GABA receptors because of the involvement of the minor tranquilizer drugs, benzodiazepines. The studies on the GABA system (metabolism, local concentrations, receptors) show great promise in the understanding and treatment of ethanol dependence and withdrawal.     

Effects of the crude venom of the social wasp Agelaia vicina on gamma-aminobutyric acid and glutamate uptake in synaptosomes from rat cerebral cortex

Glutamate (L-glu) is the most important excitatory neurotransmitter in the mammalian central nervous system. Its action is terminated by transporters located in the plasma membrane of neurons and glial cells, which have a critical role in preventing glutamate excitotoxicity under normal conditions. The neurotransmitter gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system. Venoms of solitary wasps and orb-spiders are composed of large proteins, medium-size peptides, polyamine amides (PAs), and other neuroactive components that are highly selective to nervous tissues. The abnormal operation of uptake systems is involved in several failures. Several studies indicate alterations in extracellular GABA and glutamate concentrations in epilepsy conditions that may relate to transporter functions. The effects of the crude and boiled venom of the social wasp Agelaia vicina, "cassununga," on GABA and L-glu uptake in rat cerebral cortex synaptosomes are related. The venom uncompetitively inhibited high- and low-affinity GABA uptake by 91.2% and by 76%, respectively. This kind of inhibition was also found to affect high- (99.6%) and low-affinity (90%) uptake of L-glu. These results suggest that the effects observed in these experiments indicate the venom of A. vicina to be a useful tool to further characterize GABA- and L-glu-uptake systems.     

Distribution of GABA-like immunoreactive neurons in the slug Limax maximus

Summary Immunohistochemical techniques were used to study the distribution of gamma-amino butyric acid (GABA)-like immunoreactive neurons in the nervous system of the slug Limax maximus. Approximately 170 GABA-like immunoreactive cell bodies were found in the central nervous system. These were located in the cerebral, buccal and pedal ganglia. Most GABA-like immunoreactive neurons had small cell bodies, which were aggregated into discrete clusters within the cerebral and pedal ganglia. Three pairs of longer, uniquely identifiable, GABA-like immunoreactive cells were found in the cerebral ganglion. GABA-like immunoreactive nerve fibres were also found in all of the central ganglia but were absent from peripheral nerves. These results suggest that GABA acts as a central neurotransmitter in the slug. The possible roles of GABA-ergic neurotransmission in the slug are discussed.