Institute for Neurophysiology and NeuroCure Research Center, Charité-Universitätsmedizin, Berlin, Germany.
Glia. 2011 Nov;59(11):1706-18. doi: 10.1002/glia.21217. Epub 2011 Jul 20.
Glutamine synthetase (GS) is an astrocytic enzyme, which catalyzes the synthesis of glutamine from glutamate and ammonia. In the central nervous system, GS prevents glutamate-dependent excitotoxicity and detoxifies nitrogen. Reduction in both expression and activity of GS was reported in the hippocampus of patients with temporal lobe epilepsy (TLE), and this reduction has been suggested to contribute to epileptogenesis. In this study, we characterized hippocampal GS expression in the pilocarpine model of TLE in Wistar rats by means of stereology and morphometric analysis. Neither the GS positive cell number nor the GS containing cell volume was found to be altered in different hippocampal subregions of chronic epileptic rats when compared with controls. Instead, redistribution of the enzyme at both intracellular and tissue levels was observed in the epileptic hippocampus; GS was expressed more in proximal astrocytic branches, and GS expressing astrocytic somata was located in closer proximity to vascular walls. These effects were not due to shrinkage of astrocytic processes, as revealed by glial fibrillary acidic protein staining. Our results argue for GS redistribution rather than downregulation in the rat pilocarpine model of TLE. The potential contribution of increased GS perivascular affinity to the pathogenesis of epilepsy is discussed as well.
谷氨酰胺合成酶（GS）是一种星形胶质细胞酶，可催化谷氨酸和氨合成谷氨酰胺。在中枢神经系统中，GS 可防止谷氨酸依赖性兴奋毒性并解毒氮。据报道，颞叶癫痫（TLE）患者海马体中的 GS 表达和活性降低，这种降低被认为有助于癫痫发生。在这项研究中，我们通过立体学和形态计量学分析，对 Wistar 大鼠匹罗卡品 TLE 模型中海马体 GS 表达进行了表征。与对照组相比，慢性癫痫大鼠海马体的不同亚区中 GS 阳性细胞数或含 GS 细胞体积均未改变。相反，在癫痫海马体中观察到酶在细胞内和组织水平上的重新分布；GS 在近端星形胶质细胞分支中表达更多，表达 GS 的星形胶质体细胞位于更靠近血管壁的位置。这些效应不是由于星形胶质细胞突起的收缩，如胶质纤维酸性蛋白染色所揭示的那样。我们的结果表明，在大鼠匹罗卡品 TLE 模型中，GS 重新分布而不是下调。还讨论了增加的 GS 血管周围亲和力对癫痫发病机制的潜在贡献。
