We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Bergmann glia expression of polyglutamine-expanded ataxin-7 produces neurodegeneration by impairing glutamate transport.
- Authors
Custer, Sara K.; Garden, Gwenn A.; Gill, Nishi; Rueb, Udo; Libby, Randell T.; Schultz, Christian; Guyenet, Stephan J.; Deller, Thomas; Westrum, Lesnick E.; Sopher, Bryce L.; la Spada, Albert R.
- Abstract
Non-neuronal cells may be pivotal in neurodegenerative disease, but the mechanistic basis of this effect remains ill-defined. In the polyglutamine disease spinocerebellar ataxia type 7 (SCA7), Purkinje cells undergo non-cell-autonomous degeneration in transgenic mice. We considered the possibility that glial dysfunction leads to Purkinje cell degeneration, and generated mice that express ataxin-7 in Bergmann glia of the cerebellum with the Gfa2 promoter. Bergmann glia-specific expression of mutant ataxin-7 was sufficient to produce ataxia and neurodegeneration. Expression of the Bergmann glia-specific glutamate transporter GLAST was reduced in Gfa2-SCA7 mice and was associated with impaired glutamate transport in cultured Bergmann glia, cerebellar slices and cerebellar synaptosomes. Ultrastructural analysis of Purkinje cells revealed findings of dark cell degeneration consistent with excitotoxic injury. Our studies indicate that impairment of glutamate transport secondary to glial dysfunction contributes to SCA7 neurodegeneration, and suggest a similar role for glial dysfunction in other polyglutamine diseases and SCAs.
- Subjects
NEURODEGENERATION; NEUROGLIA; CEREBELLAR ataxia; PURKINJE cells; TRANSGENIC mice; CELL death
- Publication
Nature Neuroscience, 2006, Vol 9, Issue 10, p1302
- ISSN
1097-6256
- Publication type
Article
- DOI
10.1038/nn1750