Vol. 12, Issue 6, 868-884, June 2002

Multiplex Three-Dimensional Brain Gene Expression Mapping in a Mouse Model of Parkinson's Disease

¹ Department of Molecular and Medical Pharmacology, ² Crump Institute for Molecular Imaging, School of Medicine, University of California, Los Angeles, California 90095, USA; ³ Department of Electrical Engineering, Signal and Image Processing Institute, School of Engineering, University of Southern California, Los Angeles, California 90089, USA

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 at http://www.pharmacology.ucla.edu/smithlab/genome_multiplex and at http://www.genome.org. Microarray data are also available at GEO, http://www.ncbi.nlm.nih.gov/geo, under the series accession no. GSE30.]