Chronic stress induces depression-like behavior in rats through affecting brain mitochondrial function and inflammation

Chronic stress is involved in pathophysiology of depression, and causes some neurochemical alterations in brain. Both mitochondrial dysfunction and neuroinflammation are implicated in mediating the depression-like behavior. The objectives of present study were, at first, to confirm that chronic unpredictable mild stress (CUMS) induces depression-like behavior and alters mitochondrial function and inflammatory responses within the brain, and then to explore the role of mitochondria in the development of this depression-like behavior. It has been found that CUMS exposure induced depression-like behavior, mitochondrial dysfunction, increased IL-1, IL6, IFN-gamma and TNF-alpha levels in hippocampus and PFC. Moreover, the level of ATP, the key index of mitochondrial function, was inversely correlated with the levels of proinflammatory cytokine. Intracerebroventricular (ICV) injection of the mitochondrial targeted antioxidant MnTBAP significantly alleviated depression-like behavior in CUMS group. These findings suggested that CUMS results in depression-like behavior, mitochondrial dysfunction as well as neuroinflammation, and mitochondria dysfunction contributes to depression-like behavior caused by CUMS.