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

@article{citeulike:893737, abstract = {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.}, address = {Department of Psychological Medicine, Wales College of Medicine and School of Biosciences, Cardiff University, Heath Park, Cardiff CF14 4XN, Wales, UK.}, author = {Hodges, A. and Strand, A. D. and Aragaki, A. K. and Kuhn, A. and Sengstag, T. and Hughes, G. and Elliston, L. A. and Hartog, C. and Goldstein, D. R. and Thu, D. and Hollingsworth, Z. R. and Collin, F. and Synek, B. and Holmans, P. A. and Young, A. B. and Wexler, N. S. and Delorenzi, M. and Kooperberg, C. and Augood, S. J. and Faull, R. L. and Olson, J. M. and Jones, L. and Luthi-Carter, R. }, citeulike-article-id = {893737}, issn = {0964-6906}, journal = {Hum Mol Genet}, keywords = {huntington, microarray}, month = {March}, number = {6}, pages = {965--977}, posted-at = {2006-10-12 01:54:48}, priority = {2}, title = {Regional and cellular gene expression changes in human Huntington's disease brain.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/16467349}, volume = {15}, year = {2006} }

TY - JOUR ID - citeulike:893737 L3 - citeulike-article-id:893737 TI - Regional and cellular gene expression changes in human Huntington's disease brain. JF - Hum Mol Genet VL - 15 IS - 6 SP - 965 EP - 977 AD - Department of Psychological Medicine, Wales College of Medicine and School of Biosciences, Cardiff University, Heath Park, Cardiff CF14 4XN, Wales, UK. SN - 0964-6906 N2 - 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. KW - huntington KW - microarray AU - Hodges, A AU - Strand, AD AU - Aragaki, AK AU - Kuhn, A AU - Sengstag, T AU - Hughes, G AU - Elliston, LA AU - Hartog, C AU - Goldstein, DR AU - Thu, D AU - Hollingsworth, ZR AU - Collin, F AU - Synek, B AU - Holmans, PA AU - Young, AB AU - Wexler, NS AU - Delorenzi, M AU - Kooperberg, C AU - Augood, SJ AU - Faull, RL AU - Olson, JM AU - Jones, L AU - Luthi-Carter, R PY - 2006/03/15/ UR - http://view.ncbi.nlm.nih.gov/pubmed/16467349 ER -