Gene expression profiling of socially stressed squirrel monkey brain

A.M. Karssen; J.Z. Li; S. Her; A.F. Schatzberg; D.M. Lyons
Society for Neuroscience annual meeting. 2005.


Our ongoing studies examining the effects of chronic social stress on squirrel monkey brain have shown that repeated social stimulation after isolation-induced hypercortisolism results in enhanced learning and memory performance. As part of these studies we have collected brains of socially stressed monkeys and their controls to characterize gene expression changes using microarrays. Since squirrel monkey microarrays are not available, we have used the Affymetrix human U133A 2.0 array on hippocampal and cortical brain tissue of squirrel monkey. To test feasibility of application of human microarrays on squirrel monkey brain tissue we have performed a comparison of the behaviour of squirrel monkey and human brain tissue on Affymetrix arrays. We show that although the presence call rate of squirrel monkey is generally lower than that of human tissue, the variance is much less. This comparison indicates that human microarray can be applied on squirrel monkey brain tissue to characterize changes in gene expression after chronic social stress. When examining the effects of social stimulation in various brain regions, the ventromedial prefrontal cortex shows a remarkably high number of affected genes in stressed animals compared to controls. Using a cut-off of p<0.05, fold change of 1.15 or more and a presence call on at least one array, social stimulation altered transcription of about two-fold more genes in this region than in any other brain region examined. Nearly three-fold more genes are downregulated than upregulated. Interestingly, ventromedial prefrontal cortex is critically involved in various aspects of mood and emotion regulation. Further studies will validate some of these genes and might give some new clues of genes involved in social stimulation and stress. Support Contributed By: the Pritzker Neuropsychiatric Disorders ResearchConsortium which is supported by the Pritzker Neuropsychiatric Disorders Research Fund L.L.C.. A shared intellectual property agreement ex ists between this philanthropic fund and all the universities involved.