Role Of TRPV1 In Depression-like Behavior In LPS-treated Mice:Involvement Of Microglial Inflammation Response

The Cytokines Hypothesis of depression thinks that the change of neuroplasticity induced by proinflammatory cytokines in the CNS is the important pathogenesis for depression.Microglia,as the primary immune effector cells in the CNS,regulates the signals between the nervous and the immune systems.Release cytokines is the main method of microglia to keep homeostatic.And this process is regulated by many receptor which expression in microglia,including TRPV1.The TRPV1 has been found to be involved in modulating microglial ROS generation and the release of cytokines,and takes part in multiple emotion disorders.This study makes a hypothesis that TRPV1 is involved in the NLRP3 inflammasome activation in microglia and depression-like behavior induced by LPS.We use the wild type and TRPV1 knock-out mice which both are injected LPS to study.This research has three parts.1)we detect the expression of TRPV1 in the total protein and mRNA of hippocampus,and use the immunofluorescence to confirm the location of TRPV1.2)Blocking the function of TRPV1 by gene knock-out or intracerebroventricular administration,we measure the depression-like behavior by open filed test,forced swimming test and tail suspension test to ensure the TRPV1 is involved in the depression-like behavior induced by LPS.3)The Quantitative real-time PCR and Western blot was used to determine the level of pro-inflammatory cytokines or the activity of inflammasome in hippocampus.Then primary microglia is treated by LPS and CAP to verify the mechanism which we propose in vitro.The results show that LPS-treatment increases the expression of TRPV1 in hippocampus and the phenomenon mainly occurs in microglia.Level of depression-like behavior and inflammation is reduced after blocking the function of TRPV1.The activity of inflammasome is also suppressed.The experiment that activated TRPV1 can enhance the NLRP3 assembly and the release of IL-1? in vitro further confirms our hypothesis.So we have demonstrated that TRPV1 is involved in the activation of inflammasome,then regulates depression-like behavior induced by LPS.