Transient focal cerebral ischemia significantly alters not only EAATs but also VGLUTs expression in rats: relevance of changes in reactive astroglia

短暂性局灶性脑缺血不仅显著改变大鼠的 EAAT,而且显著改变 VGLUT 的表达:反应性星形胶质细胞变化的相关性

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作者:Eduardo Sánchez-Mendoza, María C Burguete, María Castelló-Ruiz, María Pilar González, Cesáreo Roncero, Juan B Salom, Carmen Arce, Sixta Cañadas, Germán Torregrosa, Enrique Alborch, María Jesús Oset-Gasque

Abstract

The involvement of plasma membrane glutamate transporters (EAATs - excitatory aminoacid transporters) in the pathophysiology of ischemia has been widely studied, but little is known about the role of vesicular glutamate transporters (VGLUTs) in the ischemic process. We analyzed the expression of VGLUT1-3 in the cortex and caudate-putamen of rats subjected to transient middle cerebral artery occlusion. Western blot and immunohistochemistry revealed an increase of VGLUT1 signal in cortex and caudate-putamen until 3 days of reperfusion followed by a reduction 7 days after the ischemic insult. By contrast, VGLUT2 and 3 were drastically reduced. Confocal microscopy revealed an increase in VGLUT2 and 3 immunolabelling in the reactive astrocytes of the ischemic corpus callosum and cortex. Changes in VGLUTs and EAATs expression were differently correlated to neurological deficits. Interestingly, changes in VGLUT1 and EAAT2 expression showed a significant positive correlation in caudate-putamen. Taken together, these results suggest a contribution of VGLUTs to glutamate release in these structures, which could promote neuroblast migration and neurogenesis during ischemic recovery, and a possible interplay with EAATs in the regulation of glutamate levels, at least in the first stages of ischemic recovery.

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