Genomic Screening of Wistar and Wistar-Kyoto Rats Exposed to Chronic Mild Stress and Deep Brain Stimulation of Prefrontal Cortex

Abstract

Stress, a major precipitant of depression, and antidepressants have major impact on synaptic integrity and plasticity in brain areas, such as hippocampus (HPC) and prefrontal cortex (PFC). We have recently shown that, unlike Wistar rats, rats of the Wistar-Kyoto (WKY) strain fail to respond to chronic antidepressant treatment after exposure to chronic mild stress (CMS) procedure. However, deep brain stimulation (DBS) of PFC was effective in both strains. We aimed to identify genes that were affected by CMS, to determine whether their expression was normalized by DBS, and to establish whether common changes could be identified in antidepressant responsive (Wistar) and antidepressant-resistant (WKY) strains. Male Wistar and WKY rats were exposed chronically to CMS then treated acutely with DBS. A battery of behavioural tests was used to monitor recovery, followed by TaqMan screening of a panel of genes known to be involved in stress and antidepressant action. WKY showed over-expression of five genes in dorsal HPC and under-expression of seven genes in ventral HPC. Expression of three genes, Egr1, Htr7 and Mmp9 was decreased by CMS and normalized by DBS in the ventral HPC of Wistar rats. Some other changes in gene expression were identified in dorsal HPC and PFC, particularly in Wistars, that were not normalized by DBS. No effects were identified that were common to both Wistars and WKY. The difference between Wistars and WKY in the balance of overall gene expression in HPC may be relevant to the resistance of WKY rats to antidepressant drug treatment.