Bergmann glia expression of polyglutamine-expanded ataxin-7 produces neurodegeneration by impairing glutamate transport.

摘要: Non-neuronal cells may be pivotal in neurodegenerative disease, but the mechanistic basis of this effect remains ill-defined. In polyglutamine disease spinocerebellar ataxia type 7 (SCA7), Purkinje undergo non-cell-autonomous degeneration transgenic mice. We considered possibility that glial dysfunction leads to cell degeneration, and generated mice express ataxin-7 Bergmann glia cerebellum with Gfa2 promoter. glia-specific expression mutant was sufficient produce neurodegeneration. Expression glutamate transporter GLAST reduced Gfa2-SCA7 associated impaired transport cultured glia, cerebellar slices synaptosomes. Ultrastructural analysis revealed findings dark consistent excitotoxic injury. Our studies indicate impairment secondary contributes SCA7 neurodegeneration, suggest a similar role for other diseases SCAs.