Silencing of circular RNA PTP4A2 ameliorates depressive-like behaviors by inhibiting microglia activation in mice

Major depressive disorder (MDD) is a prevalent mental illness and showed a strong link with inflammation. Microglia, as the main resident immune cells, play an important role in the occurrence and development of depression. Circular RNA PTP4A2 (circPTP4A2) was highly expressed in microglia inflammation induced by oxygen glucose deprivation/reperfusion. However, whether circPTP4A2 involves in microglia inflammation in MDD is not clear. Here, chronic unpredictable stress (CUS) induced depressive behaviors and microglia activation in mouse hippocampus, accompanied by the elevated expression of circPTP4A2. Knockdown circPTP4A2 in mouse hippocampus ameliorated depressive-like behaviors and microglia activation. Moreover, CUS promoted phosphorylation of ERK, JNK and P38 in mouse hippocampus as same as LPS-exposed BV2 microglia. Only P38 phosphorylation was inhibited by circPTP4A2 knockdown in the hippocampus. P38 inhibitor, sb203580, repressed circPTP4A2 overexpression-induced inflammatory reaction in BV2 cells. These findings suggest that circPTP4A2 promotes depressive-like behaviors and microglia activation via P38 phosphorylation.