PARP14 is increased in the hippocampus of three mouse depression models and its relationship with neuroinflammation

Abstract

Objective To explore whether ADP ribose polymerase 14(PARP14) is related to depression and does it affect the inflammatory response of microglia. Methods Three kinds of mouse depression model were established to find potential relationship between the expression level of PARP14 and the change in depression-related brain areas including chronic restraint(CRS)model, chronic unpredictable mild stress(CUMS)model, lipopolysaccharide (LPS) model. Then the effect of Parp14 over-expression and knockdown on inflammatory response was examined in immortalized microglia cell line BV2. Results The expression of PARP14 increased in the hippocampal tissues of all three kinds of depression models, and the expression of PARP14 in the CRS model group was correlated with the expression level of inflammatory response factors in the tissues. The expression level of PARP14 also increased after stimulation of mouse immortalized microglia cell line BV2 by LPS .At the same time, BV2 cells with over-expression of PARP14 expressed more pro-inflammatory cytokines as a response to LPS stimulation, while those with knockdown Parp14 or treatment with PARP14 inhibitor showed the opposite results. Conclusions This study shows that the expression level of PARP14 in the hippocampus of depression model mice increased, which may enhance the level of neuroinflammation and aggravate depression-like phenotype by exacerbating the :PS induced inflammatory response of microglia cells .

Keywords

• major depressive disorder|poly adp-ribose polymerase 14(parp14)|neuroinflammation|microglia