Experimental basis for the putative role of GluR6/kainate glutamate receptor subunit in Huntington’s disease natural history.
Neurobiology of Disease. 2004-04-01; 15(3): 667-675
DOI: 10.1016/j.nbd.2003.12.010
Lire sur PubMed
1. Neurobiol Dis. 2004 Apr;15(3):667-75.
Experimental basis for the putative role of GluR6/kainate glutamate receptor
subunit in Huntington’s disease natural history.
Diguet E(1), Fernagut PO, Normand E, Centelles L, Mulle C, Tison F.
Author information:
(1)Physiologie et Physiopathologie de la Signalisation Cellulaire, UMR-CNRS 5543,
Université Victor Segalen-Bordeaux2, 33076 Bordeaux, France.
Age of onset of Huntington’s disease (HD) statistically correlates with the
length of expanded CAG repeats in the IT15 gene. However, other factors such as
polymorphism in the 3′ untranslated region of the GluR6 kainate receptor gene
subunit may contribute to variability in the age at onset. To investigate this
issue, we studied the motor disorder and related striatal damage induced by
3-nitropropionic acid (3-NP) subacute administration in GluR6 knockout mice
(GluR6(-/-)) as compared to wild-type mice. In two different age groups (6 months
and 1 year), we observed that GluR6(-/-) mice did not display more motor
impairment nor more striatal histopathological damage than GluR6(+/+) mice,
although 1-year-old GluR6(-/-) mice displayed reduced activity parameters either
at baseline or after 3-NP administration compared to GluR6(+/+). In both age
groups, GluR6(-/-) mice died earlier and displayed earlier motor symptoms during
3-NP-induced metabolic compromise, suggesting that GluR6-containing kainate
receptors may be implicated during neurodegeneration, such as in HD, rather than
in the final outcome.
DOI: 10.1016/j.nbd.2003.12.010
PMID: 15056475 [Indexed for MEDLINE]