The effect of chronic exposure to highly aggressive mice on hippocampal gene expression of non-aggressive subordinates.

Exposure to a chronic psychosocial stressor changes the behavioral and neuroendocrine response pattern and causes structural changes in the rodent hippocampus. However, the underlying molecular mechanism of these changes induced by chronic stress is largely unknown. Recently, it was shown that exposure to a dominant highly aggressive mouse in the sensory contact model induced long-lasting stress symptoms in subordinate mice genetically selected for long attack latency (LAL mice). The aim of the present study was to study the effect of chronic stress on hippocampal gene expression in these subordinate LAL mice. GeneChips (Affymetrix) were used to compare gene expression profiles of LAL mice exposed to a sensory contact stressor for 25 days and their controls (one array per mouse, n=5 per line). After this stress paradigm, 131 genes were found differentially expressed (P<0.01). Strikingly, all of these genes showed a subtle downregulation in response to a chronic stressor. Interestingly, a significant overrepresentation of genes encoding structural components of ribosomes were found, suggesting diminished protein biosynthesis in the hippocampus of chronically stressed LAL mice. In addition, several genes of the NFkappaB signaling cascade, a pathway crucially involved in neuronal viability and neurite growth, were found to be downregulated. Together, we hypothesize that reduced NFkappaB signaling and diminished protein biosynthesis form part of the molecular mechanisms by which a chronic psychosocial stressor induces structural alterations in hippocampus of LAL mice.