Chronic unpredictable stress negatively regulates hippocampal neurogenesis and promote anxious depression-like behavior via upregulating apoptosis and inflammatory signals in adult rats

Psychological and physical stress play a pivotal role in etiology of anxiety and depression. Chronic psychological and physical stress modify various physiological phenomena, as a consequence of which oxidative stress, decreased neurotransmitter level, elevated corticosterone level and altered NSC homeostasis is observed. However, the precise mechanism by which chronic stress induce anxious depression and modify internal milieu is still unknown. Herein, we show that exposure to CUS increase oxidative stress, microgliosis, astrogliosis while it reduces hippocampal NSC proliferation, neuronal differentiation and maturation in adult rats. CUS exposure in rats reduce dopamine and serotonin level in cortex and hippocampus, which result in increased anxiety and depression-like phenotypes. We also found elevated level of NF-kappa B and TNF-alpha while decreased anti-inflammatory cytokine IL-10 level, that led to increased expression of Bax and cleaved Caspase-3 whereas down regulation of antiapoptotic protein Bcl2. Additionally, CUS altered adult hippocampal neurogenesis, increased gliosis and neuronal apoptosis in cerebral cortex and hippocampus which might be associated with reduced AKT and increased ERK signaling, as seen in the rat brain tissue. Taken together, these results indicate that CUS induce oxidative stress and neuroinflammation which directly affects NSC dynamics, monoamines levels and behavioral functions in adult rats.