Wong Michael, Ess Kevin C, Uhlmann Erik J, Jansen Laura A, Li Wen, Crino Peter B, Mennerick Steven, Yamada Kelvin A, Gutmann David H
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Ann Neurol. 2003 Aug;54(2):251-6. doi: 10.1002/ana.10648.
Excessive astrocytosis in cortical tubers in tuberous sclerosis complex (TSC) suggests that astrocytes may be important for epileptogenesis in TSC. We previously demonstrated that astrocyte-specific Tsc1 gene inactivation in mice (Tsc1 cKO mice) results in progressive epilepsy. Here, we report that glutamate transporter expression and function is impaired in Tsc1 cKO astrocytes. Tsc1 cKO mice exhibit decreased GLT-1 and GLAST protein expression. Electrophysiological assays demonstrate a functional decrease in glutamate transport currents of Tsc1 cKO astrocytes in hippocampal slices and astrocyte cultures. These findings suggest that Tsc1 inactivation in astrocytes causes dysfunctional glutamate homeostasis, leading to seizure development in TSC.
结节性硬化症（TSC）中皮质结节内星形胶质细胞增生过多，提示星形胶质细胞可能在TSC的癫痫发生中起重要作用。我们之前证明，小鼠中星形胶质细胞特异性Tsc1基因失活（Tsc1条件性敲除小鼠，即Tsc1 cKO小鼠）会导致进行性癫痫。在此，我们报告Tsc1 cKO星形胶质细胞中谷氨酸转运体的表达和功能受损。Tsc1 cKO小鼠表现出GLT-1和GLAST蛋白表达降低。电生理分析表明，海马切片和星形胶质细胞培养物中Tsc1 cKO星形胶质细胞的谷氨酸转运电流功能下降。这些发现提示，星形胶质细胞中Tsc1失活会导致谷氨酸稳态功能失调，从而引发TSC中的癫痫发作。
