Neuroinflammation caused by mental stress: the effect of chronic restraint stress and acute repeated social defeat stress in mice

Objectives: Cerebrovascular disease (CVD) is the leading cause of permanent disability worldwide. Inflammation has been reported to play an important role in the progression of CVD. Neuropsychiatric disorders such as depression are associated with increased incidence of CVD epidemiologically, although the mechanisms underlying this association are not clear. In this study, we assessed the effect of the acute repeated social defeat stress (RSDS) and chronic restraint stress (CRS) on neuroinflammation in mice. Methods: A total of 40 6-week-old male C57BL/6J mice were divided into RSDS, CRS, and corresponding control groups. In the RSDS group, male C57BL/6J mice were repeatedly subjected to bouts of social defeat by a larger CD-1 mouse for 10 min daily for 10 consecutive days. In the CRS group, the mice were exposed to restraint stress for 6 h per day for 28 consecutive days. Depressive behavior was evaluated by conducting sucrose preference test over 24 h. Peripheral blood serum and brain tissues were collected for measurement of corticosterone (CORT), epinephrine (EPI), and inflammatory factors (TNF-alpha and IL-6) using ELISA or real-time PCR 24 h after the sucrose preference test. Results: Both RSDS and CRS decreased the sucrose preference ratio. The acute stress increased serum CORT and EPI, while the chronic stress did not significantly influence them. Both stress models induced an inflammatory response in peripheral serum and the brain. Conclusions: RSDS and CRS are two effective models of depressive behavior, and both models cause neuroinflammation, which may be responsible for the increased risk of CVD seen in patients with depression.