Effect of chronic intermittent restraint stress on hippocampal expression of marker proteins for synaptic plasticity and progenitor cell proliferation in rats.

Chronic restraint stress may change hippocampal mRNA levels of markers for synaptic plasticity such as synaptophysin, growth-associated protein 43 (GAP-43), and brain-derived neurotrophic factor (BDNF). In order to examine the relation between that stressor and those biochemical markers on protein level as well as the Ki-67 protein, a marker of progenitor cell proliferation, we subjected rats to chronic intermittent restraint stress for 6 h per day for 14 days excluding the weekends. This stress intensity caused a significant increase in adrenal gland weight and decrease in body weight gain. However, we did not find significant alteration of protein expression levels for synaptophysin, GAP-43, and BDNF by using Western blot analysis. Unlike these findings, the hippocampal protein expression of Ki-67 was significantly reduced by using both Western blot and immunohistochemical analyses. This reduction of Ki-67 expression in chronically stressed rats was correlated with increased adrenal gland weight and decreased body weight gain. All marker proteins used did not show any changes of hippocampal expression level after a single restraint stress session of 3 h. In conclusion, chronic intermittent restraint stress caused changes in the physiological stress response in rats, and a decrease of hippocampal progenitor cells using the Ki-67 protein as marker which indicates a suppression of adult neurogenesis. The results might contribute to understand the relationship between stress and cellular neurobiology of depression, since chronic antidepressant treatment have been shown to increase adult neurogenesis in the rat hippocampus.