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
相关论文
共 49 条
[41]   Metabotropic glutamate receptor subtypes are differentially expressed after transient cerebral ischemia without, during and after tolerance induction in the gerbil hippocampus [J].
Sommer, C ;
Roth, SU ;
Kuhn, R ;
Kiessling, M .
BRAIN RESEARCH, 2000, 872 (1-2) :172-180
[42]   STRUCTURE, EXPRESSION, AND FUNCTIONAL-ANALYSIS OF A NA+-DEPENDENT GLUTAMATE ASPARTATE TRANSPORTER FROM RAT-BRAIN [J].
STORCK, T ;
SCHULTE, S ;
HOFMANN, K ;
STOFFEL, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (22) :10955-10959
[43]   PARAVENTRICULAR NUCLEUS - A SITE FOR THE INTEGRATION OF NEUROENDOCRINE AND AUTONOMIC MECHANISMS [J].
SWANSON, LW ;
SAWCHENKO, PE .
NEUROENDOCRINOLOGY, 1980, 31 (06) :410-417
[44]   Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1 [J].
Tanaka, K ;
Watase, K ;
Manabe, T ;
Yamada, K ;
Watanabe, M ;
Takahashi, K ;
Iwama, H ;
Nishikawa, T ;
Ichihara, N ;
Hori, S ;
Takimoto, M ;
Wada, K .
SCIENCE, 1997, 276 (5319) :1699-1702
[45]  
van den Pol AN, 1998, J NEUROSCI, V18, P10749
[46]   Presynaptic modulation of glutamate release targets different calcium channels in rat cerebrocortical nerve terminals [J].
Vazquez, E ;
SanchezPrieto, J .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1997, 9 (10) :2009-2018
[47]   Neuronal death and survival in two models of hypoxic-ischemic brain damage [J].
Walton, M ;
Conner, B ;
Lawlor, P ;
Young, D ;
Sirimanne, E ;
Gluckman, P ;
Cole, G ;
Dragunow, M .
BRAIN RESEARCH REVIEWS, 1999, 29 (2-3) :137-168
[48]   Inhibition of cyclin-dependent kinases improves CA1 neuronal survival and behavioral performance after global ischemia in the rat [J].
Wang, FH ;
Corbett, D ;
Osuga, H ;
Osuga, S ;
Ikeda, JE ;
Slack, RS ;
Hogan, MJ ;
Hakim, AM ;
Park, DS .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2002, 22 (02) :171-182
[49]   Effect of glutamate transporter on neuronal damage induced by photochemical thrombotic brain ischemia [J].
Yan, YP ;
Yin, KJ ;
Sun, FY .
NEUROREPORT, 1998, 9 (03) :441-446