Journal
JOURNAL OF CELL BIOLOGY
Volume 171, Issue 6, Pages 1001-1012Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200508072
Keywords
-
Categories
Funding
- NIA NIH HHS [AG19206, R01 AG019206] Funding Source: Medline
- NINDS NIH HHS [R01 NS036232, NS36232] Funding Source: Medline
Ask authors/readers for more resources
Huntington disease ( HD) is characterized by the preferential loss of striatal medium-sized spiny neurons ( MSNs) in the brain. Because MSNs receive abundant glutamatergic input, their vulnerability to excitotoxicity may be largely influenced by the capacity of glial cells to remove extracellular glutamate. However, little is known about the role of glia in HD neuropathology. Here, we report that mutant huntingtin accumulates in glial nuclei in HD brains and decreases the expression of glutamate transporters. As a result, mutant huntingtin (htt) reduces glutamate uptake in cultured astrocytes and HD mouse brains. In a neuron-glia coculture system, wild-type glial cells protected neurons against mutant htt-mediated neurotoxicity, whereas glial cells expressing mutant htt increased neuronal vulnerability. Mutant htt in cultured astrocytes decreased their protection of neurons against glutamate excitotoxicity. These findings suggest that decreased glutamate uptake caused by glial mutant htt may critically contribute to neuronal excitotoxicity in HD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available