In the central nervous system, Asiaticoside has been shown to attenuatein vitro neuronal damage caused by exposure toβ-amyloid.In vivo studies demonstrated that Asiaticoside could attenu-ate neurobehavioral, neurochemical and histological changes in transient focal middle cerebral artery occlusion animals. In addition, Asiaticoside showed anxiolytic effects in acute and chronic stress animals. However, its potential neuroprotective properties in glutamate-induced excito-toxicity have not been fully studied. We investigated the neuroprotective effects of Asiaticoside in primary cultured mouse cortical neurons exposed to glutamate-induced excitotoxicity invoked by N-methyl-D-aspartate. Pretreatment with Asiaticoside decreased neuronal cell loss in a con-centration-dependent manner and restored changes in expression of apoptotic-related proteins Bcl-2 and Bax. Asiaticoside pretreatment also attenuated the upregulation of NR2B expression, a subunit of N-methyl-D-aspartate receptors, but did not affect expression of NR2A subunits. Additionally, in cultured neurons, Asiaticoside significantly inhibited Ca2+ influx induced by N-methyl-D-aspartate. These experimental ifndings provide preliminary evidence that during excitotoxicity induced by N-methyl-D-aspartate exposure in cultured cortical neurons, the neu-roprotective effects of Asiaticoside are mediated through inhibition of calcium inlfux. Aside from its anti-oxidant activity, down-regulation of NR2B-containing N-methyl-D-aspartate receptors may be one of the underlying mechanisms in Asiaticoside neuroprotection.

谷氨酸受体对大鼠海马兴奋性氨基酸的调节作用

谷氨酸(glutamate)和天冬氨酸(asparte)在正常的学习、记忆及癫癎发作和神经退行性疾病的病理过程中均起着很重要的作用.海马中含有大量谷氨酸和天冬氨酸,且与学习记忆关系密切,同时它对缺血、缺氧和某些化学致害剂等致病因素较为敏感 [1-2].为了探讨脑内谷氨酸和天冬氨酸释放的调节机制,特别是了解海马内兴奋性氨基酸的释放过程,我们于2004年8月至2005年4月采用脑微透析技术结合高效液相色谱技术研究N-甲基-D-天冬氨酸(N-metlyl-D-asparte,NMDA)受体对大鼠海马谷氨酸和天冬氨酸释放的调节作用,报道如下.

抗精神兴奋剂成瘾的药物及其分子机理

精神兴奋剂滥用是一个重大的医学问题.可卡因、苯丙胺、甲基苯丙胺、以及N-甲基-3,4-亚甲基二氧基甲基苯丙胺(N-methyl-3,4-methylenedioxymethamphetamine,MDMA)是常见的精神兴奋剂.反复使用精神兴奋剂会引起药物依赖.药物依赖的核心症状是持续存在的药物渴求及其导致的复吸行为,许多神经递质和神经调节系统参与了这一过程.例如:多巴胺(dopamine,DA)、谷氨酸(glutamate,Glu)、γ一氨基丁酸(γ-aminobutyric acid,GABA)、内源性大麻素(endocannabinoids,eCBs)、5-羟色胺(serotonin,5-hydroxytryptamine,5-HT)以及阿片(opioid)受体.醋胆素、一些神经肽和其他神经信号传导通路也参与了兴奋剂成瘾过程.

Objective　To investigate the effect of D-AP5 (D-2-amino-5-phosphonopentanoate, a specific NMDA-antagonist) on the increase of intracellular free Ca2+ concentration (［Ca2+］i) induced by glutamate in isolated cochlear inner hair cells (IHCs), and to detect the autoreceptors of the IHC membrane. Methods　When a laser scanning confocal microscope (LSCM) was used, the exogenous glutamate (Glu)-induced changes in ［Ca2+］i of isolated IHCs and OHCs of guinea pig cochlea were observed with fluo-3, a fluorescent probe for ［Ca2+］i. After D-AP5 or CNQX (6--cyano--7--nitroguinoxaline--2, 3--dione, a specific AMPA- antagonist) was administrated, the exogenous glutamate (Glu)-induced changes in ［Ca2+］i of isolated IHCs were recorded. Results　In the presence of a low concentration Glu (3.85?μmol/L), there was an increase of ［Ca2+］i in IHCs, whereas there was no change in OHCs. When 50?μmol/L of D-AP5 was administrated in advance, Glu did not induce a corresponding increase in ［Ca2+］i in IHCs, and 50?μmol/L of CNQX did not completely block the increase of ［Ca2+］i in IHCs. Conclusions　These results suggest that the autoreceptors existing in the IHC membrane are mainly of NMDA type, while there are relatively few AMPA receptors. Exogenous Glu is capable of increasing ［Ca2+］i in IHCs by acting on the NMDA autoreceptor of IHCs in a positive feedback manner.