Chronic Unpredictable Stress Decreases Cell Proliferation in the Cerebral Cortex of the Adult Rat

Abstract

One of the most consistent morphologic findings in postmortem studies of brain tissue from depressed patients is a decrease in the number of glia in the prefrontal cortex. However, little is known about the mechanisms that contribute to this decrease in cell number. To address this question, we subjected adult rats to chronic stress, a vulnerability factor for depression, and measured cell proliferation as a potential cellular mechanism that could underlie glial reduction in depression. We found that exposure to chronic unpredictable stress (CUS) for 15 days significantly decreased cell proliferation in neocortex by approximately 35%. This effect was dependent on the duration, intensity and type of stress, and was region-specific. Analysis of cell phenotype demonstrated that there was a decrease in the number of oligodendrocytes and endothelial cells. Finally, using a CUS paradigm that allows for analysis of anhedonia, we found that chronic antidepressant administration reversed the decrease in cortical cell proliferation, as well as the deficit in sucrose preference. These findings are consistent with the possibility that decreased cell proliferation could contribute to reductions in glia in prefrontal cortex of depressed subjects and further elucidate the cellular actions of stress and antidepressants.