Journal
NEUROBIOLOGY OF DISEASE
Volume 29, Issue 3, Pages 515-528Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2007.11.008
Keywords
Parkinson disease; alpha-synuclein; Microarray; substantia nigra; laser capture microdissection; mouse; transcription
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Funding
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P50NS038372] Funding Source: NIH RePORTER
- NINDS NIH HHS [NS38372, P50 NS038372, P50 NS038372-05] Funding Source: Medline
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Alpha-synuclein has been implicated in Parkinson disease, yet the mechanism by which alpha-synuclein causes cell injury is not understood. Using a transgenic mouse model, we evaluated the effect of alpha-synuclein overexpression on gene expression in the substantia nigra. Nigral mRNA from wild type and alpha-synuclein transgenic mice was analyzed using Affymetrix gene arrays. At 3 months, before pathological changes are apparent, we observed modest alterations in gene expression. However, nearly 200 genes were altered in expression at 9 months, when degenerative changes are more apparent. Functional genomic analysis revealed that the genes altered at 9 months were predominantly involved in gene transcription. As in human Parkinson disease, gene expression changes in the transgenic model were also modulated by gender. These data demonstrate that alterations of gene expression are widespread in this animal model, and suggest that transcriptional dysregulation may be a disease mechanism that can be targeted therapeutically. (c) 2007 Elsevier Inc. All rights reserved.
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