03 Jul 2002

Researchers at the University of California, Los Angeles, and the University of Southern California have developed a new technique coined “voxelation” to generate three-dimensional maps of gene expression in the brain. The method uses the power of DNA microarray technology to probe 3D cubes, or voxels, that are dissected from whole brains by precise surgical techniques. The group, led by Desmond Smith, used the method to analyze 9,000 genes from 40 such voxels removed from normal mice and from mice with methamphetamine-induced neurodegeneration resembling Parkinson’s disease. Their results are published in the June Genome Research.

By comparing expression patterns among 20 voxels in each hemisphere, first author Brown et al, were able to demonstrate some interesting patterns of gene expression. As would be expected, they found a strong correlation between corresponding voxels in the left and right side of the brain, thus confirming the accuracy of the voxelation procedure. But they were also able to detect regional differences that allowed them to correlate the expression of gene clusters with specific areas of the brain. Furthermore, analysis of non-coding regions revealed regulatory sequences that may be responsible for expression of these clusters.

The authors found clear expression differences between normal and PD mice. Differentially expressed genes included those involved in signal transduction, metabolism, vesicular transport, cell morphology, and transcription. By refining their technique Brown et al. were able to find gross spatial differences between diseased and wild type brains that suggest a shift in expression away from the striatum and cerebellum and toward the hippocampus. An analysis of the genes responsible for this shift may prove interesting.—Tom Fagan