Dehydroepiandrosterone's antiepileptic action in FeCl3-induced epileptogenesis involves upregulation of glutamate transporters
Dehydroepiandrosterone's antiepileptic action in FeCl3-induced epileptogenesis involves upregulation of glutamate transporters
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DOI：
10.1016/j.eplepsyres.2013.06.008
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发表时间：
2013-09-01
影响因子：
2.2
通讯作者：
Sharma, Deepak
中科院分区：
文献类型：
--
作者：
Mishra, Monika;Singh, Rameshwar;Sharma, Deepak
脱氢表雄酮（DHEA）是一种神经活性雄激素类固醇，在铁诱导的实验性癫痫（模拟创伤后临床癫痫）中具有抗癫痫作用。在铁诱导的癫痫中，由于转运蛋白（神经胶质和/或神经元）的下调（表达减少）而导致的谷氨酸摄取减少导致的细胞外谷氨酸增加在癫痫发生期间是活跃的。本研究旨在确定DHEA的抗癫痫作用机制是否涉及谷氨酸转运体的上调（表达增加）。通过向大鼠大脑皮层注射FeCl 3，在大鼠中进行铁诱导的癫痫发生。给铁致痫大鼠腹腔注射DHEA 7、14和21天。谷氨酸转运蛋白mRNA的表达水平，采用定量PCR在海马铁诱导癫痫的慢性期。在癫痫发生过程中谷氨酸转运体mRNA显著减少。DHEA处理导致谷氨酸转运体：GLT-1、GLAST和EACC-1 mRNA的显著升高，表明DHEA处理诱导这些转运体的上调。这一结果对神经甾体抗癫痫作用机制的研究以及谷氨酸转运体作为神经甾体能性癫痫治疗靶点具有重要意义。(C)2013爱思唯尔有限公司版权所有。
Dehydroepiandrosterone (DHEA), a neuroactive androgen steroid, has antiepileptic action in iron-induced experimental epilepsy (which models post-traumatic clinical epilepsy). In iron-induced epilepsy increased extracellular glutamate resulting from its reduced ghat uptake due to the down-regulation (decreased expression) of transporters (glial and or neuronal) is active during epileptogenesis. The present study was aimed at determining whether the mechanism of antiepileptic action of DHEA involved upregulation (increased expression) of glutamate transporters. Iron-induced epileptogenesis was performed in rats by FeCl3 injection into the cerebral cortex. DHEA was administered intraperitoneally to the iron-induced epileptic rats for 7, 14 and 21 days. Levels of glutamate transporters mRNAs expression were measured using quantitative PCR in the hippocampus during the chronic phase of iron-induced epileptogenesis. There were significant reductions in the glutamate transporter mRNAs in epileptogenesis. DHEA treatment resulted in a significant elevation of glutamate transporters: GLT-1, GLAST and EACC-1 mRNA indicating that the DHEA treatment induced upregulation of these transporters. The results are of significance in respect of the mechanism of the antiepileptic action of neurosteroids and the glutamate transporters as therapeutic targets in glutamatergic epileptogenesis. (C) 2013 Elsevier B.V. All rights reserved.