Down-regulation of the glial glutamate transporter GLT-1 in rat hippocampus and striatum and its modulation by a group III metabotropic glutamate receptor antagonist following transient global forebrain ischemia

被引:56
作者
Chen, JC
Hong, HC
Lu, JL
Chiang, YC
Huang, HM
Wang, HL
Wu, T
Liao, JJ
Yeh, TS
机构
[1] Chang Gung Univ, Dept Pharmacol, Tao Yuan, Kwei Shan, Taiwan
[2] Chang Gung Univ, Dept Physiol, Tao Yuan, Kwei Shan, Taiwan
[3] Chang Gung Mem Hosp, Dept Neurol, Lin Kao, Taiwan
关键词
transient global ischemia; delayed neuronal death; hippocampal CA1; striatum; GLT-1; metabotropic glutamate receptor;
D O I
10.1016/j.neuropharm.2005.05.002
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Our goals were to identify biochemical markers for transient global ischemia-induced delayed neuronal death and test possible drug therapies against this neuronal damage. Four-vessel occlusion (4-VO) for 20 min was used as a rat model. The temporal expression profiles of three glutamate transporters (GLT-1, GLAST and EAAC1) were evaluated in the CA1 region of the hippocampus and the striatum. The protein levels of the GLT-1 were significantly down-regulated between 3 and 6 h after ischemia-reperfusion in the CA1 region and striatum, returned to the control (2-VO) levels 24 h after reperfusion and remained unchanged for up to 7 days. The levels of GLAST in the CA1 region and striatum, and EAAC1 in the CA1 region did not change after ischemia from 1 h to 7 days. Pretreatment with group III metabotropic glutamate receptor antagonist s-alpha-MCPA (20 mu g/5 mu l) 30 min prior to 4-VO significantly restored the GLT-1 levels in the CA1 region caused by global ischemia at both 3 and 6 h after reperfusion. The loss of pyramidal neurons in the CA1 region due to ischemia-reperfusion could also be prevented by intraventricular pretreatment with s-alpha-MCPA. The current findings pinpoint the significance of GLT-1 during ischemia/reperfusion and suggest a potential application of group III metabotropic glutamate receptor antagonist against ischemic/hypoxic neuronal damage. (c) 2005 Published by Elsevier Ltd.
引用
收藏
页码:703 / 714
页数:12
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