Multiplex three-dimensional brain gene expression mapping in a mouse model of Parkinson's disease

Vanessa M. Brown, Alex Ossadtchi, Arshad H. Khan, Simon Yee, Goran Lacan, William P. Melega, Simon R Cherry, Richard M. Leahy, Desmond J. Smith

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

To facilitate high-throughput 3D imaging of brain gene expression, a new method called voxelation has been developed. Spatially registered voxels (cubes) are analyzed, resulting in multiple volumetric maps of gene expression analogous to the images reconstructed in biomedical imaging systems. Using microarrays, 40 voxel images for 9000 genes were acquired from brains of both normal mice and mice in which a pharmacological model of Parkinson's disease (PD) had been induced by methamphetamine. Quality-control analyses established the reproducibility of the voxelation procedure. The investigation revealed a common network of coregulated genes shared between the normal and PD brain, and allowed identification of putative control regions responsible for these networks. In addition, genes involved in cell/cell interactions were found to be prominently regulated in the PD brains. Finally, singular value decomposition (SVD), a mathematical method used to provide parsimonious explanations of complex data sets, identified gene vectors and their corresponding images that distinguished between normal and PD brain structures, most pertinently the striatum.

Original languageEnglish (US)
Pages (from-to)868-884
Number of pages17
JournalGenome Research
Volume12
Issue number6
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Genetics

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