Hardin-Pouzet H, Krakowski M, Bourbonnière L, Didier-Bazes M, Tran E, Owens T
Neuroimmunology Unit, Montreal Neurological Institute, Québec, Canada.
Glia. 1997 May;20(1):79-85. doi: 10.1002/(sici)1098-1136(199705)20:1<79::aid-glia8>3.0.co;2-0.
Experimental allergic encephalomyelitis (EAE) was induced in SJL/J mice by adoptive transfer of MBP-reactive T cells in order to investigate the role of astrocytes in pathology. GFAP protein and mRNA expression (analyzed using semiquantitative Western blot and RT-PCR techniques) were upregulated in the spinal cord of mice, which had developed a complete paralysis of hind- and fore-limbs and tail (grade 4 EAE), thus establishing that reactive gliosis occurred under these experimental conditions. Within the same samples and using similar techniques, we found that glutamine synthetase (GS) and glutamate dehydrogenase (GDH) expression were dramatically reduced. These two astrocytic enzymes are responsible for degradation of glutamate, the most abundant excitatory neurotransmitter in the brain. Since elevated levels of glutamate may be neurotoxic, we propose that the decreased capacity of astrocytes to metabolize glutamate may contribute to EAE pathology.
为了研究星形胶质细胞在病理学中的作用，通过过继转移髓鞘碱性蛋白（MBP）反应性T细胞，在SJL/J小鼠中诱导实验性自身免疫性脑脊髓炎（EAE）。在已经出现后肢、前肢和尾巴完全麻痹（4级EAE）的小鼠脊髓中，胶质纤维酸性蛋白（GFAP）的蛋白质和mRNA表达（使用半定量蛋白质免疫印迹和逆转录聚合酶链反应技术进行分析）上调，从而证实了在这些实验条件下发生了反应性胶质增生。在相同样本中并使用类似技术，我们发现谷氨酰胺合成酶（GS）和谷氨酸脱氢酶（GDH）的表达显著降低。这两种星形胶质细胞酶负责降解脑中最丰富的兴奋性神经递质谷氨酸。由于谷氨酸水平升高可能具有神经毒性，我们认为星形胶质细胞代谢谷氨酸能力的下降可能导致EAE病理学改变。
