海洛因使大鼠背侧海马功能和GIu／GABA递质系统紊乱

目的探讨海洛因依赖对大鼠背侧海马神经元功能以及海马谷氨酸（Glu）和γ-氨基丁酸（GABA）递质系统的影响。方法按剂量逐日递增原则,1日2次,连续9d皮下注射海洛因建立其依赖SD大鼠模型。采用玻璃微电极细胞外记录大鼠海马神经元自发放电,比较放电形式和频率的变化。并用氨基酸自动分析仪测定大鼠海马Glu和GABA含量。结果海洛因依赖组大鼠背侧海马神经元放电以中频（51．02％）、单个不匀（61．22％）为主,对照组则以低频（58．70％）为主,形式分布均一（P〈0．05）;海洛因对腹侧海马神经元放电无影响（P〉0．05）;依赖大鼠海马Glu含量下降,GABA含量增加（P〉0．05）,Glu／GABA比值低于对照组（P〈0．05）。结论海洛因更易损伤大鼠背侧海马神经元功能;Glu／GABA递质系统的紊乱可能是海洛因损害大鼠学习记忆能力的机制之一。     

氧乐果致猫脑区Glu和GABA的时间变化

目的建立氧乐果皮下染毒急性猫中毒模型,观察急性中毒后脑组织谷氨酸(Glu)和γ-氨基丁酸(GABA)免疫阳性细胞的时空分布规律及形态变化。方法将30只健康猫分为2组。染毒组25只:腹部皮下4点等量注射40%氧乐果0.3 ml/kg(=2.1 mg/kg)。对照组5只:腹部皮下4点等量注射同体积体积分数为0.9%的生理盐水。应用免疫组化的方法观察Glu和GABA免疫阳性细胞的变化。结果免疫组织化学染色观察染毒后顶叶、海马、基底节和小脑Glu阳性细胞数与对照组比较,差异无显著性,顶叶GABA阳性细胞染色加深,阳性细胞数对照组为(9.8±1.2)个/视野,染毒后3h阳性细胞数(14.7±3.3)个/视野,并在染毒后各时间点与对照组比较,差异有显著性。结论氧乐果染毒后顶叶GABA的含量增加。     

GABA受体基因多态性与海洛因依赖的相关性研究进展

海洛因依赖受遗传基因和环境的相互作用。γ-氨基丁酸(γ-aminobutyric acid,GABA)是脑内主要抑制性神经递质。现有研究表明GABA受体参与海洛因依赖的发生与发展过程,故GABA受体基因值得作为海洛因依赖遗传易感相关的候选基因予以评价。本文综述近年来对GABA受体基因多态性与海洛因依赖相关性研究的进展情况。     

丙泊酚对大鼠海马突触体释放谷氨酸和γ-氨基丁酸的影响

目的观察丙泊酚对大鼠海马突触体谷氨酸和γ氨基丁酸(GABA)Ca2+依赖性释放和非Ca2+依赖性释放的影响。方法制备突触体后用人工脑脊液(aCSF)孵育,分为7组,应用丙泊酚(propofol)的浓度分别为3(Pro3组)、10(Pro10组)、30(Pro30组)、100(Pro100组)和300μmol·L-1(Pro300组),脂肪乳剂对照组加入脂肪乳(Intralipid组),空白对照组(Control组)不加入任何药物。在观察Ca2+依赖性释放时,加入二氢海人藻酸和哌啶酸;在观察非Ca2+依赖性释放的时候,去除aCSF中的Ca2+。在37℃的条件下,应用20μmol·L-1藜芦定或30mmol·L-1KCl诱发递质释放。应用反相高效液相色谱法测定aCSF中谷氨酸和GABA的浓度。结果①Ca2+依赖性递质释放:应用藜芦定时,Pro30、Pro100和Pro300组的谷氨酸和GABA释放量低于Intralipid组(P<0.01或P<0.05);应用KCl时,各组的谷氨酸和GABA释放量无差异(P>0.05)。②非Ca2+依赖性释放:各组应用藜芦定和KCl诱发的谷氨酸和GABA释放量无差异(P>0.05)。结论丙泊酚可以抑制Ca2+依赖性谷氨酸和GABA的释放,而对非Ca2+依赖性谷氨酸和GABA释放无影响。     

帕金森病患者血浆Glu和GABA水平与睡眠障碍的相关性研究

目的:探讨帕金森病(PD)患者血浆谷氨酸(Glu)、γ氨基丁酸(GABA)水平与睡眠障碍的相关性。方法:选择2014年12月—2016年10月门诊及住院的PD患者82例,对其进行匹兹堡睡眠质量指数评分(PSQI),根据PSQI评分总分>5分和≤5分分为睡眠障碍组和无睡眠障碍组,同时对PD患者进行帕金森氏病综合评分量表(UPDRS)评分及H-Y分级评分并测定血浆氨基酸神经递质水平,分析Glu和GABA与PSQI评分的关系。结果:入选的82例PD患者中,存在睡眠障碍者43例,占52.44%;两组患者之间的性别、年龄、病程、H-Y分级及UPDRSⅢ评分比较,差异无统计学意义(P>0.05);睡眠障碍组Glu与GABA水平要显著低于无睡眠障碍组,差异有统计学意义(P<0.05);PD患者的PSQI与Glu(r=-0.348,P<0.05)和GABA(r=-0.428,P<0.05)呈负相关。结论:Glu和GABA水平的降低与PD患者的睡眠障碍具有一定的相关性。     

脑室注射生长抑素或GABA对大鼠痛阈和脑内GABA或生长抑素含量的影响(英文)

目的:研究脑内Som和GABA的相互影响及其与痛觉调制的关系.方法:应用放射免疫,氨基酸分析仪和痛阈测定法.结果:发现Som 10 μg icv可使大鼠海马,脑干内GABA含量显著减少,分别由对照组的2.3±0.3和2.2±0.4 μmol g~(-1)降至1.6±0.4和1.5±0.2μmol g~(-1),痛阈由对照组的4.2±0.2 s升高到7.0±1.1 s;半胱胺600 μg icv降低脑内Som后,海马和脑干内GABA含量也明显减少,但痛阈不变.GABA 1500 μg icv后,痛阈变化不明显,而海马、脑干内Som含量均显著减少,分别由对照组的55±4和84 4 ng g~(-1)降至37±5和55±6 ng g~(-1)这一效应可被荷包牡丹碱10 μg阻断;以异烟肼300 mg kg~(-1)降低脑内GABA后,海马和脑干内Som含量即明显增多.结论:脑内Som和GABA之间存在着相互抑制作用,但与它们在痛觉调制中的作用无关.     

HPLC测定大鼠海马中谷氨酸、γ-氨基丁酸的含量

目的 建立了邻苯二甲醛(OPA)柱前衍生高效液相荧光色谱法检测大鼠海马中谷氨酸(GLU)、γ-氨基丁酸(GABA)含量的方法。方法 采用Alltima C₁₈色谱柱(4.6 mm×250 mm,5 μm),流动相为50 mmol·L^-1乙酸钠(pH 6.8)、甲醇、四氢呋喃梯度洗脱,流速1.0 mL·min^-1。激发波长(λ_Ex)338 nm,发射波长(λ_Em)425 nm。结果 GLU、GABA线性范围分别为1.03~20.6 μg·mL^-1(r=0.999 2)和1.13~22.6 μg·mL^-1(r=0.999 7);当信噪比为3时,GLU和GABA的检出限分别为5.27×10^-4μg·mL^-1和7.35×10^-4 μg·mL^-1;测得精密度RSD分别为3.4%和3.5%;加样回收率分别为90%~96%,85%~91%。结论 本方法简便、准确、灵敏,特异性强,重复性好,适用于海马中GLU和GABA的含量测定。     

HPLC测定大鼠海马中谷氨酸、γ-氨基丁酸的含量

目的建立了邻苯二甲醛（OPA）柱前衍生高效液相荧光色谱法检测大鼠海马中谷氨酸（GLU）、γ-氨基丁酸（GABA）含量的方法。方法采用AlltimaC18色谱柱（4.6mm×250mm,5μm）,流动相为50mmol·L^-1乙酸钠（pH6.8）、甲醇、四氢呋喃梯度洗脱,流速1.0mL·min^-1。激发波长（λEx）338nm,发射波长（λEm）425nm。结果GLU、GABA线性范围分别为1.03～20.6μg·mL^-1（r=0.9992）和1.13～22.6μg·mL^-1（r=0.9997）;当信噪比为3时,GLU和GABA的检出限分别为5.27×10-4μg·mL^-1和7.35×10-4μg·mL^-1;测得精密度RSD分别为3.4%和3.5%;加样回收率分别为90%～96%,85%～91%。结论本方法简便、准确、灵敏,特异性强,重复性好,适用于海马中GLU和GABA的含量测定。     

GABA对雄性大鼠下丘脑GnRH和血清睾酮含量的影响

雄性大鼠脑室注射γ-氨基丁酸(GABA),用放射免疫分析(RIA)测定下丘脑内侧基底部(MBH)处促性腺激素释放激素(GnRH)和血清睾酮(T)含量的变化。结果表明脑室注射GA-BA0.0103(μg/20u1只)40min后,下丘脑MBH处GnRH与血清睾酮含量均降低,GABA与血清睾酮水平存在时间,剂量依从性关系。由此推测,GABA可能是作用于下丘脑-垂体-睾丸轴,通过抑制下丘脑(GnRH)的释放,进而降低血清睾酮的含量。     

头孢曲松对甲基苯丙胺致大鼠行为及纹状体氨基酸等递质含量改变的影响

目的观察甲基苯丙胺(METH)急性处理时致神经损伤情况,以及纹状体中氨基酸类神经递质谷氨酸(glutamate,Glu)、单胺类神经递质多巴胺(dopamine,DA)及其代谢产物DOPAC的变化。方法建立METH急性毒性模型,同时利用药物头孢曲松进行干预,利用清醒动物脑微透析技术检测神经递质含量的变化。结果 METH急性给药组与盐水对照组相比,刻板行为明显增加(P<0.01);急性给予METH后,胞外Glu浓度持续增加,在本试验检测时间(0～6 h)范围内,与基础平衡值相比,在给药5.5 h时Glu浓度已增加450%。胞外DA水平在1 h达峰值,与基础平衡值相比,浓度增加1248.6%。与METH组相比,头孢曲松预防给药可明显降低大鼠纹状体胞外Glu浓度(P<0.05)。结论 METH急性处理能引起纹状体中胞外谷氨酸的含量明显增加,导致神经损伤;METH的神经毒性与兴奋性氨基酸的过度释放密切相关。     

托吡酯对原代培养海马神经元癫痫样放电的抑制效应

目的:探讨托吡酯对原代培养海马神经元癫痫样放电的抑制作用及其特点。方法:分离原代培养 1日龄SD大鼠海马神经元,d9~15采用膜片钳全细胞模式记录托吡酯 ( 20, 100μmol·L-1 )和苯妥英 (10μmol·L-1 )对电流刺激及谷氨酸诱导神经元癫痫样放电的抑制效应。结果:苯妥英(10μmol·L-1 )、托吡酯(20, 100μmol·L-1 )抑制电流刺激诱导神经元动作电位,分别减少 100 %,(38±25) %和 ( 70±19 ) %。苯妥英 ( 10μmol·L-1 )及托吡酯(100μmol·L-1 )分别完全或部分抑制谷氨酸诱导海马神经元的癫痫样放电。结论:托吡酯抑制原代培养海马神经元的癫痫样放电,并与其浓度及作用时间有关。     

丙泊酚对全脑缺血大鼠海马CA1区神经病理学和谷氨酸转运体1表达的影响

目的 观察丙泊酚对全脑缺血大鼠海马CA1区谷氨酸转运体1(GLT-1)表达的影响。方法 采用四血管闭塞法建立全脑缺血模型;脑缺血前3 h静脉输注丙泊酚90 mg·kg^-1,首次剂量(总剂量的1/3)15 min内推注,剩余剂量持续输注1 h。脑缺血再灌注后于0, 12, 24, 48 h和7 d取材。光镜下观察海马CA1区的组织学分级和神经元密度, Western印迹法检测海马CA1区GLT-1的表达。结果 组织学分级结果显示,假手术组及丙泊酚对照组所有动物均为0级,脑缺血模型组有5只动物均为Ⅲ级。丙泊酚+脑缺血组中3只动物的组织学分级为0级,2只动物为Ⅰ级。假手术组及丙泊酚对照组神经元密度分别为185±12及(181±11 )mm^-1。模型组中锥体细胞几乎全部死亡。与脑缺血组相比,丙泊酚+脑缺血组神经元密度为(125±14)mm^-1,说明存活细胞数显著增高(P<0.05)。Western印迹结果显示,与同一时间点的假手术组相比, 脑缺血后12 h,GLT-1的表达显著增强(0.31±0.03 vs 0.38±0.04), 随后逐渐降低,在脑缺血后7 d显著低于假手术组(0.19±0.03 vs 0.29±0.04)。丙泊酚对照组GLT-1的表达保持在较高的水平(0.47±0.05),直到7 d才降至假手术组水平0.29±0.03。在再灌注后24和48 h时,丙泊酚明显逆转脑缺血造成的GLT-1表达的下降, GLT-1表达分别为0.45±0.04 vs 0.29±0.04和0.47±0.05 vs 0.27±0.04(P<0.05),在7 d时与假手术组相当。结论 丙泊酚可保护海马CA1区的锥体细胞抵御缺血打击,并上调了大鼠海马CA1区GLT-1的表达。     

氯胺酮麻醉期间大鼠脑内氨基酸递质水平的变化

氨基酸类递质是主要的中枢神经递质之一 ,对于精神意识活动的调整起着关键作用。现认为全麻药 (尤吸入全麻药 )可通过抑制突触前谷氨酸 (Ｇｌｕ)的释放、增强谷氨酸的再摄取及阻滞突触后兴奋性氨基酸受体而发挥全麻作用[1] 。药物对于天冬氨酸 (Ａｓｐ)、γ 氨基丁酸 (ＧＡＢＡ)和甘氨酸(Ｇｌｙ)的突触前作用则较为复杂 ,不如谷氨酸明显和统一[2 ] ,可能不是全麻药的主要作用部位。有些学者认为氯胺酮对各类氨基酸类递质的摄取与释放过程无明显影响[2 ] ,这些都是离体实验的结论 ,活体动物在麻醉状态下 ,中枢神经系统中的氨基酸类递质水平是…     

加巴喷丁对癫痫持续状态大鼠海马区神经元凋亡的影响

目的研究加巴喷丁(GBP)对癫痫持续状态(SE)大鼠海马区神经元凋亡的影响。方法SD大鼠48只随机分为对照组、戊四氮致痫组(PTZ组)、GBP组、GBP干预组(干预组),每组12只。戊四氮溶液60 mg.kg-1.d-1腹腔注射诱发SE。干预组致痫后给予GBP 600 mg.kg-1.d-1;GBP组仅给予GBP 600 mg.kg-1.d-1;对照组和PTZ组给予0.9%氯化钠溶液灌胃。采用头皮针状电极单极导联法观察大鼠痫性放电的脑电图。缺口末端标记法(TUNEL)检验凋亡阳性细胞。结果 TUNEL阳性细胞在PTZ组显著高于对照组(P<0.01);GBP组与对照组比较差异无统计学意义(P>0.05);干预组表达低于PTZ组(P<0.05)。结论戊四氮致SE大鼠海马CA1和CA3区神经元TUNEL阳性细胞显著增加,GBP能显著减少TUNEL阳性细胞。     

Involvement of the prefrontal cortex but not the dorsal hippocampus in the attention-enhancing effects of nicotine in rats

Rationale Nicotine can enhance attentional performance in humans, a property that may be of therapeutic utility. Objectives To identify brain sites mediating nicotine-induced attentional enhancement. Methods Nicotine (0, 1, 2, 4 and 8 μg) was injected bilaterally into the dorsal hippocampus and the prelimbic area of the prefrontal cortex, brain sites implicated in cognitive functions, of rats performing the five-choice serial reaction time task (5-CSRTT). This rodent model of attention required the detection of light stimuli presented randomly in one of five locations during 30-min sessions. Systemically administered nicotine (0.1 and 0.2 mg/kg SC) was tested alongside local injections as a positive control. Results Nicotine (SC) enhanced response accuracy, reduced omission errors and shortened response latency. Nicotine injected into the dorsal hippocampus had no effect on any measure of performance except a slight decrease in latency in some animals at lower doses. By contrast, local injections of nicotine into the prefrontal cortex caused a dose-related increase in accuracy, the measure most closely reflecting stimulus detection and attention. Nicotine also increased omission errors selectively in the first 10 min of sessions and slightly reduced premature responding in the intertrial interval. No effects on response latency were observed. Conclusions The results implicate the prefrontal cortex, but not the dorsal hippocampus, in the attention-enhancing effects of nicotine. The targeting of nicotinic receptor subtypes expressed in the prefrontal cortex may be of particular benefit for the treatment of chronic disease states characterised by attentional dysfunction.     

海马M_2受体调节杏仁核内谷氨酸的释放与学习记忆的研究

目的研究海马内M1和M2受体对学习记忆功能的影响及其可能机制。方法SD大鼠分为3组,分别海马内注射等体积的M1-ASODN(M1-AS组)、M2-ASODN(M2-AS组)和生理盐水(对照组),以被动逃避反应的步入潜伏期作为衡量学习记忆功能的指标,以CZE-LIFD法检测杏仁核内游离谷氨酸的浓度。结果M1-ASODN缩短步入潜伏期,为对照组的25%(P<0.01),M2-ASODN使步入潜伏期较对照组增加了75%(P<0.05)。双侧海马内注射ASODN后与对照组相比,M2-AS组杏仁核内谷氨酸的含量增加164%(P<0.01),而M1-AS组无变化(P>0.05)。结论海马内M受体参与恐惧性记忆的调节,M2受体抑制学习记忆,M1受体促进学习记忆。海马内M2受体可能通过调节杏仁核内谷氨酸含量的变化介导被动逃避反应的记忆过程。     

Characterization of extracellular GABA in the substantia nigra reticulata by means of brain microdialysis

Summary Brain microdialysis was used to characterize extracellular gamma-aminobutyric acid (GABA) in the substantia nigra reticulata (SNR) of freely moving rats. The extracellular GABA in the SNR was characterized using acutely implanted probes (4–8 h after surgery; day 1) and chronically implanted probes (24 h after surgery; day 2).3-Mercaptopropionic acid, a glutamic acid decarboxylase inhibitor, was used to identify GABA. This drug induced an immediate decrease in the extracellular GABA levels to 40% of basal values, suggesting that the detected GABA is, at least in part, newly synthesized.The basal levels of extracellular GABA measured either on day 1 or day 2 were not affected by infusion of micromolar amounts of tetrodotoxin. Therefore, a direct coupling between GABA dialysate concentrations and nerve-impulse flow does not seem to exist. Infusion of the GABA uptake inhibitor nipecotic acid (0.5 mmol/l) resulted in a 4-fold increase in the dialysate levels of GABA lasting at least for 3 h on both days. K⁺ stimulation (60 mmol/l) increased extracellular GABA levels in the SNR to 450% of basal values. This effect again did not differ significantly on day 1 and day 2.The origin of the extracellular GABA in the SNR, as recorded by microdialysis under the two experimental conditions, is discussed.Send offprint requests to W. Timmerman at the above address     

康脑液预处理对脑缺血再灌注损伤大鼠脑组织的谷氨酸/氨基丁酸比值的影响

目的 观察康脑液对局灶性脑缺血再灌注损伤大鼠脑组织中氨基酸类神经递质的的影响.方法 将60只大鼠随机分为6组:假手术组,模型组,康脑液低、中、高剂量组,依达拉奉组.用栓线法复制大鼠大脑中动脉栓塞模型,缺血2h再灌注1h后,断头取脑,用2,4-二硝基氟苯柱前衍生法,测定大鼠脑组织中Glu与γ-GABA含量.结果 与假手术组相比,模型组大鼠脑组织中Glu和γ -GABA含量均明显上升,Glu/GABA明显升高(P＜0.05);与模型组比较,康脑液能够不同程度地降低大鼠脑组织中Glu含量,降低γ-GABA含量,使Glu/GABA趋于正常,具有显著性差异(P＜0.05).结论 康脑液可能通过降低缺血再灌注损伤大鼠脑组织中Glu含量及Glu/GABA比值从而发挥脑保护作用.     

Anxiogenic effect of CCK8s in the ventral hippocampus of rats: possible involvement of GABA(A) receptors

Cholecystokinin (CCK) as an important neuropeptide in the brain has been implicated in the modulation of anxiety. The effects of this neurotransmitter on anxiety-like behavior in the ventral hippocampus have not been evaluated yet. Moreover, some evidences show a functional interaction between GABA and CCK in the nervous system. Bilateral injections of three doses of CCK8s (0.01, 0.05 and 0.1 μg/rat) into the ventral hippocampus decreased percentage of open arm time (%OAT) and open arm entries (%OAE) that are representative of anxiogenic-like behavior in the elevated plus-maze test of anxiety. Bilateral injections of LY225910, a selective CCK(2) receptor antagonist, at the doses of 0.01, 0.1 and 0.5 μg/rat did not change anxiety-related parameters. Administration of muscimol, a selective GABA(A) receptor agonist, at the doses of 0.001, 0.005 and 0.01 μg/rat produced dose dependent increase in %OAT and %OAE indicating an anxiolytic-like effect, while administration of bicuculline, a selective GABA(A) receptor antagonist, at the doses of 0.1, 0.2 and 0.5 μg/rat decreased %OAT and %OAE showing that this drug promoted anxious behavior of the rats. Co-administration of bicuculline (0.2 μg/rat) with CCK8s decreased the anxiogenic effects of CCK8s. Furthermore, co-administration of LY225910 (0.5 μg/rat) with muscimol increased the anxiolytic effect of muscimol at the dose of 0.001 μg/rat. The results of this study suggest that both CCK and GABAergic system have important and opposite roles in the modulation of anxiety-like behavior in the ventral hippocampus of rats and they may have a complex interaction in the ventral hippocampus to modulate anxiety-related behavior.     

Perfusion with carbon monoxide does not affect extracellular glutamate in dialysates of the hippocampus of freely moving mice

Carbon monoxide (CO) produces several neurological effects, including cognitive, mood, and behavioral disturbance. Glutamate is thought to play a particularly important role in learning and memory. Thus, the present study was aimed at investigating the local effect of CO on the glutamate level in the hippocampus of mice using in vivo reverse microdialysis. Mice were perfused with Ringer’s solution (control) or CO (60–125?μM) in Ringer’s solution into the hippocampus via microdialysis probe. Dialysate samples were collected every 20?min, and then analyzed with high-performance liquid chromatography coupled to an electrochemical detector. The result revealed that the perfusion with CO had no significant effect on glutamate levels (p?=?0.316) as compared to the control group. This finding does not support a local CO rise as the cause of the increased glutamate level in the hippocampus of mice.