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

European Journal of Neuroscience - Tập 10 Số 3 - Trang 976-988 - 1998
Kei Watase1,2, Kouichi Hashimoto3,4, Masanobu Kano4, Keiko Yamada5, Masahiko Watanabe5, Yoshiro Inoue5, Shigeru Okuyama6, Takashi Sakagawa7, Shinichi Ogawa6, Noritaka Kawashima6, Seiji Hori8, Masato Takimoto8, Keiji Wada1, Kohichi Tanaka1
1Department of Degenerative Neurological Diseases, National Institute of Neuroscience, Kodaira, Tokyo 187, Japan,
2Japan Science and Technology Corporation, Kawaguchi-Center Building, 4-1-8 Hon-cho, Kawaguchi, Saitama, Japan
3Department of Physiology, Jichi Medical School, Minamikawachi-machi, Tochigi-ken, 329-04, Japan
4Laboratory for Neuronal Signal Transduction, Frontier Research Program, The Institute of Physical and Chemical Research (RIKEN), Wako, Saitama 351-01, Japan,
5Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060, Japan
61st Laboratory Medicinal Research Laboratories,
7Laboratory of Animal Center, Taisho Pharmaceutical Co. Ltd, Yoshino-cho, Ohmiya, Saitama 330, Japan,
8International Research Laboratories, Ciba-Geigy Japan, 10-66, Miyuki-cho, Takarazuka 665, Japan,

Tóm tắt

AbstractTo 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.

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