Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice.
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.
Watase
K
K
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, Kodaira, Tokyo, Japan.
Hashimoto
K
K
Kano
M
M
Yamada
K
K
Watanabe
M
M
Inoue
Y
Y
Okuyama
S
S
Sakagawa
T
T
Ogawa
S
S
Kawashima
N
N
Hori
S
S
Takimoto
M
M
Wada
K
K
Tanaka
K
K
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000502:physiology*; D000595:Amino Acid Sequence; D027322:Amino Acid Transport System X-AG; D000818:Animals; D002531:Cerebellum / Q000033:anatomy & histology / Q000293:injuries* / Q000502:physiology; D003080:Cold Temperature / Q000009:adverse effects; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology*; D009412:Nerve Fibers / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D004856:Postural Balance / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology*
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D018698:Glutamic Acid