MCPIP1 alleviates depressive‑like behaviors in mice by inhibiting the TLR4/TRAF6/NF‑κB pathway to suppress neuroinflammation

Lipopolysaccharide‑induced (LPS) neuroinflammation serves an important role in the development of depression. Monocyte chemotactic protein‑1‑induced protein 1 (MCPIP1, also known as ZC3H12A and Regnase‑1) possesses endoribonuclease and Deubiquitinase activities. In the present study, the effects of MCPIP1 on LPS‑induced 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 LPS‑induced depressive‑like 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)/NF‑κB signaling pathway. The results indicated that MCPIP1 accelerated M2‑polarization of microglia and alleviated depressive‑like behaviors of mice via the inhibition of the TLR4/TRAF6/NF‑κB signaling pathway.

depression; hippocampus; inflammation; lipopolysaccharide; microglia polarization; monocyte chemotactic protein‑1‑induced protein 1.