MCPIP1 alleviates depressive­like behaviors in mice by inhibiting the TLR4/TRAF6/NF­κB pathway to suppress neuroinflammation.

Lipopolysaccharide­induced (LPS) neuroinflammation serves an important role in the development of depression. Monocyte chemotactic protein­1­induced protein 1 (MCPIP1, also known as ZC3H12A and Regnase­1) possesses endoribonuclease and deubiquitinase activities. In the present study, the effects of MCPIP1 on LPS­induced depression were assessed. A mouse model of hippocampal neuroinflammation was established by intraperitoneal injection of LPS. Microglia were treated with LPS, MCPIP1 overexpression vector, MCPIP1 knockdown vector or TLR4 inhibitor. MCPIP1 alleviated LPS­induced depressive­like behaviors. MCPIP1 facilitated M2 polarization of microglia. MCPIP1 attenuated the inflammatory response in microglia via inhibition of the TLR4/TNF receptor associated factor 6 (TRAF6)/NF­κB signaling pathway. The results indicated that MCPIP1 accelerated M2­polarization of microglia and alleviated depressive­like behaviors of mice via the inhibition of the TLR4/TRAF6/NF­κB signaling pathway.