The study revealed that rhythmic genes regulate depression caused by neuroinflammation by controlling chematist factors.

Depression is a complex mental illness caused by the interaction of genes and environment.previous studies have shown that depression patients generally have sleep disorders, and the rhythm of stress hormone corticosterone secretion is abnormal, which indicates that rhythm plays an important role in depression; in addition, a large number of research evidence shows that neuroinflammation is an important factor in the occurrence of depression.interestingly, microglia, the main executor of immune function in the central nervous system, regularly express inflammatory factors and rhythm genes, suggesting that there may be interaction between rhythm and inflammation in the central nervous system.researchers from Lin Wenjuan, Key Laboratory of mental health, Institute of psychology, Chinese Academy of Sciences, conducted research on the above problems to explore whether rhythm genes affect neuroinflammation induced depression through regulating inflammatory factors.in this study, C57BL / 6J mice with circadian gene per2 knockout and wild-type mice of the same strain were used in this study. The neuroinflammatory depression model was established by injecting lipopolysaccharide (LPS) into microinjection pump with brain stereotactic technique, and saline was injected as control.the results showed that mice with per2 gene deletion could resist neuroinflammation induced depression like behavior (as shown in Figure 1).the expression of MCP-1 and RANTES in hippocampus and medial prefrontal lobe of LPS wild-type mice was higher than that of other groups, while the expression of MIP-1? Was only different in hippocampus, but there was no difference in medial prefrontal lobe, suggesting that the function of MIP-1? In specific brain regions was different. Direct injection of RANTES could significantly increase the immobility time in forced swimming behavior test Met RANTES, an antagonist of RANTES, reversed this depressive behavior, suggesting that exposure to chemokines can directly lead to depressive like behavior (as shown in Figure 2).in the expression of rhythm gene, there was no difference in the expression of per2 and BMAL1 genes between LPS injection and saline injection, but the expression of BMAL1 gene in per2 knockout mice and LPS injection group was significantly lower than that in other groups, suggesting that BMAL1 gene exerts its antidepressant like behavior induced by neuritis by regulating per2 gene (as shown in Fig. 3).the combination of BMAL1 and RANTES promoter provides direct evidence that rhythm gene regulates inflammatory factors and then affects the occurrence of depression (as shown in Figure 4).in conclusion, this study demonstrates that the deletion of per2 gene can resist the depression like behavior caused by neuroinflammation, and the mechanism is that RANTES, the downstream inflammatory factor, can not be activated, thus avoiding the occurrence of depressive behavior caused by neuritis.this study confirmed for the first time the mechanism of rhythm immune interaction in depression and provided a new idea for the treatment of inflammatory related depression.the project was funded by the National Natural Science Foundation of China (no.91132728, 31741062) and the Key Laboratory of mental health, Chinese Academy of Sciences. The research results were published online in the FASEB Journal.Fig.1 wild type mice showed shorter open arm stay time in elevated cross maze test and longer immobility time in forced swimming and tail suspension tests, suggesting depression like behavior, while per2 knockout mice did not show such behavior. 2. Changes in chemokine expression and effects of RANTES on depression like behavior in mice Fig. 3 Expression of circadian genes in wild-type or per2 knockout mice injected with LPS and saline respectively Fig. 4 binding of BMAL1 and RANTES promoter: Institute of psychology, Chinese Academy of Sciences