Yi Jae-Hyuk, Herrero Raquel, Chen Gang, Hazell Alan S
Department of Medicine, University of Montreal, Montreal, Quebec, Canada.
Brain Res. 2007 Jun 18;1154:200-5. doi: 10.1016/j.brainres.2007.04.011. Epub 2007 Apr 10.
Functional impairment of glutamate transporters contributes to excitotoxic damage and exacerbation of injury in certain neurodegenerative disorders. Several high-affinity sodium-dependent glutamate transporters have been cloned thus far. Of these, EAAT4 is abundantly expressed in Purkinje cells of the cerebellum in rats. However, little is currently known regarding levels of EAAT4 following traumatic brain injury (TBI). In this study, EAAT4 changes were examined for up to 7 days after moderate fluid-percussion by immunoblotting and immunohistochemistry. TBI caused a 20% and 25% increase in EAAT4 levels in the injured hippocampus at day 3 and day 7 following the insult. Immunohistochemical analysis revealed this increase to be localized in cells exhibiting morphological characteristics of astrocytes. In addition, increased EAAT4 immunoreactivity was observed in astrocytes in the ipsilateral cortex and cerebellum at day 3 post-injury that persisted up to 7 days after the insult. Given the reported novel characteristics of chloride conductance displayed by this transporter, our findings of increased EAAT4 levels suggest this protein may play an important role in the pathophysiology of TBI.
谷氨酸转运体的功能障碍会导致兴奋性毒性损伤，并在某些神经退行性疾病中加重损伤。到目前为止，已经克隆出了几种高亲和力的钠依赖性谷氨酸转运体。其中，EAAT4在大鼠小脑的浦肯野细胞中大量表达。然而，目前对于创伤性脑损伤（TBI）后EAAT4的水平了解甚少。在本研究中，通过免疫印迹和免疫组织化学方法，对中度液压冲击伤后长达7天的EAAT4变化进行了检测。创伤性脑损伤导致损伤后第3天和第7天，损伤海马中EAAT4水平分别升高20%和25%。免疫组织化学分析显示，这种升高定位于具有星形胶质细胞形态特征的细胞中。此外，在损伤后第3天，同侧皮质和小脑中的星形胶质细胞中观察到EAAT4免疫反应性增加，这种增加在损伤后持续长达7天。鉴于该转运体显示出氯离子传导的新特性，我们关于EAAT4水平升高的研究结果表明，这种蛋白可能在创伤性脑损伤的病理生理学中起重要作用。
