Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice

Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice
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DOI:
10.1046/j.1460-9568.1998.00108.x
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发表时间:
1998-03
影响因子:
3.4
通讯作者:
K. Watase;K. Hashimoto;M. Kano;Keiko Yamada;Masahiko Watanabe;Y. Inoue;S. Okuyama;T. Sakagawa;S. Ogawa;N. Kawashima;Seiji Hori;M. Takimoto;K. Wada;Kohichi Tanaka
K. Watase;K. Hashimoto;M. Kano;Keiko Yamada;Masahiko Watanabe;Y. Inoue;S. Okuyama;T. Sakagawa;S. Ogawa;N. Kawashima;Seiji Hori;M. Takimoto;K. Wada;Kohichi Tanaka
中科院分区:
医学3区
文献类型:
--
作者:
K. Watase;K. Hashimoto;M. Kano;Keiko Yamada;Masahiko Watanabe;Y. Inoue;S. Okuyama;T. Sakagawa;S. Ogawa;N. Kawashima;Seiji Hori;M. Takimoto;K. Wada;Kohichi Tanaka

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为了研究小脑Bergmann星形胶质细胞中高表达的谷氨酸转运蛋白GLAST的功能,将小鼠GLAST基因失活。GLAST缺陷小鼠发育正常,可以完成简单的协调任务,例如停留在静止或缓慢旋转的杆上,但未能完成更具挑战性的任务,例如停留在快速旋转的杆上。电生理检查显示,即使在成年阶段,突变小鼠的浦肯野细胞仍然是由攀爬纤维的多重神经支配。我们还发现突变小鼠小脑损伤后水肿体积显著增加。这些结果表明,GLAST在小脑爬行纤维突触的形成和防止急性脑损伤后兴奋性毒性小脑损伤中起积极作用。
To study the function of GLAST, a glutamate transporter highly expressed in the cerebellar Bergmann astrocytes, the mouse GLAST gene was inactivated. GLAST‐deficient mice developed normally and could manage simple coordinated tasks, such as staying on a stationary or a slowly rotating rod, but failed more challenging task such as staying on a quickly rotating rod. Electrophysiological examination revealed that Purkinje cells in the mutant mice remained to be multiply innervated by climbing fibres even at the adult stage. We also found that oedema volumes in the mutant mice increased significantly after cerebellar injury. These results indicate that GLAST plays active roles both in the cerebellar climbing fibre synapse formation and in preventing excitotoxic cerebellar damage after acute brain injury.