Inducible ablation of astrocytes shows that these cells are required for neuronal survival in the adult brain
Inducible ablation of astrocytes shows that these cells are required for neuronal survival in the adult brain
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作者：
Cui, W;Allen, ND;Clark, AJ
为了研究星形胶质细胞在成人大脑中的功能，我们在GFAP启动子的控制下，将大肠杆菌硝基还原酶（E. coli nitroreductase， NTR）的表达靶向于转基因小鼠的星形胶质细胞。给药CB1954后，选择性消融表达NTR的星形胶质细胞，导致运动失调。组织学检查显示，脑内受影响最严重的区域是小脑，其中伯格曼胶质细胞消失，颗粒神经元变性。对浦肯野细胞树突也有特殊的影响，这些神经元与颗粒层之间的连接被破坏。星形胶质细胞消融与谷氨酸转运蛋白表达的急剧减少有关，这可能解释了颗粒神经元的变性，因为谷氨酸的兴奋毒性作用导致了类似的表型。这些结果首次证明星形胶质细胞在体内对成人大脑神经元的存活很重要。(C) 2001 Wiley-Liss, Inc。
To study the function of astrocytes in the adult brain, we have targeted the expression of E. coli nitroreductase (NTR) to the astrocytes of transgenic mice under the control of the GFAP promoter. The astrocytes expressing NTR were selectively ablated after administration of the prodrug CB1954, resulting in motor discoordination. Histological examination showed that the region most affected in the brain was the cerebellum, in which the Bergmann glia were eliminated and the granular neurons had degenerated. Specific effects were also noted on the dendrites of the Purkinje cells, and the junction between these neurons and granular layer was disrupted. Astrocyte ablation was associated with a dramatic decrease in the expression of glutamate transporters, which may account for the degeneration of granular neurons since the excitotoxic effects of glutamate result in a similar phenotype. These results provide the first evidence that astrocytes are important for the survival of neurons in the adult brain in vivo. (C) 2001 Wiley-Liss, Inc.