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dc.contributor.authorFaideau, Mathildeen_US
dc.contributor.authorKim, Jinhoen_US
dc.contributor.authorCormier, Kerryen_US
dc.contributor.authorGilmore, Richarden_US
dc.contributor.authorWelch, Mackenzieen_US
dc.contributor.authorAuregan, Gwennaelleen_US
dc.contributor.authorDufour, Noelleen_US
dc.contributor.authorGuillermier, Martineen_US
dc.contributor.authorBrouillet, Emmanuelen_US
dc.contributor.authorHantraye, Philippeen_US
dc.contributor.authorDéglon, Nicoleen_US
dc.contributor.authorFerrante, Robert J.en_US
dc.contributor.authorBonvento, Gillesen_US
dc.date.accessioned2012-01-09T15:36:58Z
dc.date.available2012-01-09T15:36:58Z
dc.date.copyright2010en_US
dc.date.issued2010-05-21en_US
dc.identifier.citationFaideau, Mathilde, Jinho Kim, Kerry Cormier, Richard Gilmore, Mackenzie Welch, Gwennaelle Auregan, Noelle Dufour, Martine Guillermier, Emmanuel Brouillet, Philippe Hantraye, Nicole Déglon, Robert J. Ferrante, Gilles Bonvento. "In Vivo Expression of Polyglutamine-Expanded Huntingtin by Mouse Striatal Astrocytes Impairs Glutamate Transport: A Correlation with Huntington's Disease Subjects" Human Molecular Genetics 19(15): 3053-3067. (2010)en_US
dc.identifier.issn1460-2083en_US
dc.identifier.urihttp://hdl.handle.net/2144/2825
dc.description.abstractHuntington's disease (HD) is a neurodegenerative disorder previously thought to be of primary neuronal origin, despite ubiquitous expression of mutant huntingtin (mHtt). We tested the hypothesis that mHtt expressed in astrocytes may contribute to the pathogenesis of HD. To better understand the contribution of astrocytes in HD in vivo, we developed a novel mouse model using lentiviral vectors that results in selective expression of mHtt into striatal astrocytes. Astrocytes expressing mHtt developed a progressive phenotype of reactive astrocytes that was characterized by a marked decreased expression of both glutamate transporters, GLAST and GLT-1, and of glutamate uptake. These effects were associated with neuronal dysfunction, as observed by a reduction in DARPP-32 and NR2B expression. Parallel studies in brain samples from HD subjects revealed early glial fibrillary acidic protein expression in striatal astrocytes from Grade 0 HD cases. Astrogliosis was associated with morphological changes that increased with severity of disease, from Grades 0 through 4 and was more prominent in the putamen. Combined immunofluorescence showed co-localization of mHtt in astrocytes in all striatal HD specimens, inclusive of Grade 0 HD. Consistent with the findings from experimental mice, there was a significant grade-dependent decrease in striatal GLT-1 expression from HD subjects. These findings suggest that the presence of mHtt in astrocytes alters glial glutamate transport capacity early in the disease process and may contribute to HD pathogenesis.en_US
dc.description.sponsorshipCommissariat à l'énergie atomique et aux énergies alternative; Centre National de la Recherche Scientifique; National Institutes of Health (NS045806, NS058793); United States Veterans Administration; European Community's Seventh Framework Programme (FP7/2007-2013, HEALTH-F5-2008-222925)en_US
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.rightsCopyright The Author 2010. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/2.5/en_US
dc.titleIn Vivo Expression of Polyglutamine-Expanded Huntingtin by Mouse Striatal Astrocytes Impairs Glutamate Transport: A Correlation with Huntington's Disease Subjectsen_US
dc.typearticleen_US
dc.identifier.doi10.1093/hmg/ddq212en_US
dc.identifier.pubmedid20494921en_US
dc.identifier.pmcid2901144en_US


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Copyright The Author 2010. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright The Author 2010. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.