Journal Article

Regional and cellular gene expression changes in human Huntington's disease brain

Angela Hodges, Andrew D. Strand, Aaron K. Aragaki, Alexandre Kuhn, Thierry Sengstag, Gareth Hughes, Lyn A. Elliston, Cathy Hartog, Darlene R. Goldstein, Doris Thu, Zane R. Hollingsworth, Francois Collin, Beth Synek, Peter A. Holmans, Anne B. Young, Nancy S. Wexler, Mauro Delorenzi, Charles Kooperberg, Sarah J. Augood, Richard L.M. Faull, James M. Olson, Lesley Jones and Ruth Luthi-Carter

in Human Molecular Genetics

Volume 15, issue 6, pages 965-977
Published in print March 2006 | ISSN: 0964-6906
Published online February 2006 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddl013
Regional and cellular gene expression changes in human Huntington's disease brain

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Huntington's disease (HD) pathology is well understood at a histological level but a comprehensive molecular analysis of the effect of the disease in the human brain has not previously been available. To elucidate the molecular phenotype of HD on a genome-wide scale, we compared mRNA profiles from 44 human HD brains with those from 36 unaffected controls using microarray analysis. Four brain regions were analyzed: caudate nucleus, cerebellum, prefrontal association cortex [Brodmann's area 9 (BA9)] and motor cortex [Brodmann's area 4 (BA4)]. The greatest number and magnitude of differentially expressed mRNAs were detected in the caudate nucleus, followed by motor cortex, then cerebellum. Thus, the molecular phenotype of HD generally parallels established neuropathology. Surprisingly, no mRNA changes were detected in prefrontal association cortex, thereby revealing subtleties of pathology not previously disclosed by histological methods. To establish that the observed changes were not simply the result of cell loss, we examined mRNA levels in laser-capture microdissected neurons from Grade 1 HD caudate compared to control. These analyses confirmed changes in expression seen in tissue homogenates; we thus conclude that mRNA changes are not attributable to cell loss alone. These data from bona fide HD brains comprise an important reference for hypotheses related to HD and other neurodegenerative diseases.

Journal Article.  7516 words.  Illustrated.

Subjects: Genetics and Genomics

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