Bergmann glia expression of polyglutamine-expanded ataxin-7 produces neurodegeneration by impairing glutamate transport View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-08-27

AUTHORS

Sara K Custer, Gwenn A Garden, Nishi Gill, Udo Rueb, Randell T Libby, Christian Schultz, Stephan J Guyenet, Thomas Deller, Lesnick E Westrum, Bryce L Sopher, Albert R La Spada

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. More... »

PAGES

1302-1311

Journal

TITLE

Nature Neuroscience

ISSUE

10

VOLUME

9

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nn1750

DOI

http://dx.doi.org/10.1038/nn1750

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16936724


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62 disease
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64 effect
65 expression
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68 glia
69 glial dysfunction
70 glutamate transport
71 glutamate transporter GLAST
72 impaired glutamate transport
73 impairment
74 injury
75 mechanistic basis
76 mice
77 mutant ataxin-7
78 neurodegeneration
79 neurodegenerative diseases
80 non-neuronal cells
81 polyglutamine diseases
82 polyglutamine-expanded ataxin-7
83 possibility
84 promoter
85 role
86 similar role
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90 transgenic mice
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