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Regulation of astrocyte glutamate transporter-1 (GLT1) and aquaporin-4 (AQP4) expression in a model of epilepsy

机译：癫痫模型中星形胶质细胞谷氨酸转运蛋白1（GLT1）和水通道蛋白4（AQP4）表达的调节

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Astrocytes regulate extracellular glutamate and water homeostasis through the astrocyte-specific membrane proteins glutamate transporter-1 (GLT1) and aquaporin-4 (AQP4), respectively. The role of astrocytes and the regulation of GLT1 and AQP4 in epilepsy are not fully understood. In this study, we investigated the expression of GLT1 and AQP4 in the intrahippocampal kainic acid (IHKA) model of temporal lobe epilepsy (TLE). We used real-time polymerase chain reaction (RT-PCR), Western blot, and immunohistochemical analysis at 1, 4, 7, and 30 days after kainic acid-induced status epilepticus (SE) to determine hippocampal glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes), GLT1, and AQP4 expression changes during the development of epilepsy (epileptogenesis). Following IHKA, all mice had SE and progressive increases in GFAP immunoreactivity and GFAP protein expression out to 30 days post-SE. A significant initial increase in dorsal hippocampal GLT1 immunoreactivity and protein levels were observed 1 day post SE and followed by a marked downregulation at 4 and 7 days post SE with a return to near control levels by 30 days post SE. AQP4 dorsal hippocampal protein expression was significantly downregulated at 1 day post SE and was followed by a gradual return to baseline levels with a significant increase in ipsilateral protein levels by 30 days post SE. Transient increases in GFAP and AQP4 mRNA were also observed. Our findings suggest that specific molecular changes in astrocyte glutamate transporters and water channels occur during epileptogenesis in this model, and suggest the novel therapeutic strategy of restoring glutamate and water homeostasis.
机译：星形胶质细胞分别通过星形胶质细胞特异性膜蛋白谷氨酸转运蛋白1（GLT1）和水通道蛋白4（AQP4）调节细胞外谷氨酸和水稳态。星形胶质细胞在癫痫中的作用以及GLT1和AQP4的调控尚不完全清楚。在这项研究中，我们调查了颞叶癫痫（TLE）的海马内海藻酸（IHKA）模型中GLT1和AQP4的表达。我们在海藻酸诱导的癫痫持续状态（SE）后第1、4、7和30天使用实时聚合酶链反应（RT-PCR），蛋白质印迹和免疫组化分析来确定海马胶质纤维酸性蛋白（GFAP，活性星形胶质细胞的标记），GLT1和AQP4的表达在癫痫发展过程中发生变化（癫痫发生）。在IHKA之后，所有小鼠SE均发生SE，并且SE后30天GFAP免疫反应性和GFAP蛋白表达逐渐增加。 SE后1天观察到背海马GLT1免疫反应性和蛋白质水平显着增加，随后SE后4天和7天显着下调，SE后30天恢复到接近对照水平。 SE后1天，AQP4背海马蛋白表达显着下调，随后SE逐渐恢复至基线水平，SE后30天同侧蛋白水平显着增加。还观察到GFAP和AQP4 mRNA的瞬时增加。我们的发现表明，在该模型的癫痫发生过程中，星形胶质细胞谷氨酸转运蛋白和水通道发生了特定的分子变化，并提出了恢复谷氨酸和水稳态的新治疗策略。

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