Transcriptional dysregulation in a transgenic model of Parkinson disease

Talene A. Yacoubian, Ippolita Cantuti-Castelvetri, Bérengère Bouzou, Georgios Asteris, Pamela J. McLean, Bradley T. Hyman, David G. Standaert

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)515-528
Number of pages14
JournalNeurobiology of Disease
Volume29
Issue number3
DOIs
StatePublished - Mar 1 2008

Keywords

  • Alpha-synuclein
  • Laser capture microdissection
  • Microarray
  • Mouse
  • Parkinson disease
  • Substantia nigra
  • Transcription

ASJC Scopus subject areas

  • Neurology

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  • Cite this

    Yacoubian, T. A., Cantuti-Castelvetri, I., Bouzou, B., Asteris, G., McLean, P. J., Hyman, B. T., & Standaert, D. G. (2008). Transcriptional dysregulation in a transgenic model of Parkinson disease. Neurobiology of Disease, 29(3), 515-528. https://doi.org/10.1016/j.nbd.2007.11.008