胶质细胞谷氨酸转运体GLT-1的反义敲低，而非神经元谷氨酸转运体EAAC1的反义敲低，会加剧短暂性局灶性脑缺血诱导的大鼠脑神经元损伤。
Antisense knockdown of the glial glutamate transporter GLT-1, but not the neuronal glutamate transporter EAAC1, exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brain.
作者信息
Rao V L, Dogan A, Todd K G, Bowen K K, Kim B T, Rothstein J D, Dempsey R J
机构信息
Department of Neurological Surgery and Cardiovascular Research Center, University of Wisconsin-Madison, Madison, Wisconsin 53792, USA.
出版信息
J Neurosci. 2001 Mar 15;21(6):1876-83. doi: 10.1523/JNEUROSCI.21-06-01876.2001.
Abstract
Transient focal cerebral ischemia leads to extensive neuronal damage in cerebral cortex and striatum. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. This study evaluated the functional role of the glial (GLT-1) and neuronal (EAAC1) glutamate transporters in mediating ischemic neuronal damage after transient middle cerebral artery occlusion (MCAO). Transient MCAO in rats infused with GLT-1 antisense oligodeoxynucleotides (ODNs) led to increased infarct volume (45 +/- 8%; p < 0.05), worsened neurological status, and increased mortality rate, compared with GLT-1 sense/random ODN-infused controls. Transient MCAO in rats infused with EAAC1 antisense ODNs had no significant effect on any of these parameters. This study suggests that GLT-1, but not EAAC1, knockdown exacerbates the neuronal death and thus neurological deficit after stroke.
摘要
短暂性局灶性脑缺血会导致大脑皮质和纹状体广泛的神经元损伤。谷氨酸转运体的正常功能可清除突触释放的谷氨酸，以防止兴奋性毒性导致的神经元死亡。本研究评估了胶质细胞（GLT-1）和神经元（EAAC1）谷氨酸转运体在短暂性大脑中动脉闭塞（MCAO）后介导缺血性神经元损伤中的作用。与注入GLT-1正义/随机寡脱氧核苷酸（ODN）的对照组相比，给大鼠注入GLT-1反义寡脱氧核苷酸（ODN）后进行短暂性MCAO，会导致梗死体积增加（45±8%；p<0.05）、神经功能状态恶化以及死亡率升高。给大鼠注入EAAC1反义ODN后进行短暂性MCAO，对这些参数均无显著影响。本研究表明，敲低GLT-1而非EAAC1会加剧中风后的神经元死亡，进而导致神经功能缺损。
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