Multiplex Three-Dimensional Brain Gene Expression Mapping in a Mouse Model of Parkinson's Disease
- Vanessa M. Brown1,2,
- Alex Ossadtchi3,
- Arshad H. Khan1,2,
- Simon Yee1,
- Goran Lacan1,
- William P. Melega1,
- Simon R. Cherry1,2,4,
- Richard M. Leahy3, and
- Desmond J. Smith1,2,5
- 1Department of Molecular and Medical Pharmacology, 2Crump Institute for Molecular Imaging, School of Medicine, University of California, Los Angeles, California 90095, USA; 3Department of Electrical Engineering, Signal and Image Processing Institute, School of Engineering, University of Southern California, Los Angeles, California 90089, USA
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.
[All study results and supplementary data are available on the web athttp://www.pharmacology.ucla.edu/smithlab/genome_multiplex and athttp://www.genome.org. Microarray data are also available at GEO,http://www.ncbi.nlm.nih.gov/geo, under the series accession no. GSE30.]
Footnotes
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↵4 Present address: Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
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↵5 Corresponding author.
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E-MAIL DSmith{at}mednet.ucla.edu; FAX (310) 825-6267.
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Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.229002. Article published online before print in May 2002.
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- Received December 8, 2001.
- Accepted March 25, 2002.
- Cold Spring Harbor Laboratory Press
