The Protective Effects of GPR55 Against Hippocampal Neuroinflammation and Neurogenic Damage in CSDS Mice

BackgroundDepression is one of the most prevalent mental illnesses in the world today, the onset of depression is usually accompanied by neuroinflammation and neurogenic damage. Recently, G protein coupled receptor 55 (GPR55) has been associated with mood regulation as a third kind of cannabinoid receptor, and the activation of GPR55 was demonstrated recently to have a neuroprotective effect on hippocampal neurogenesis against inflammatory insult. However, its role in regulating depression and anxiety remains poorly understood.Methods10-day chronic social defeat stress (CSDS) was utilized as an animal model of depression to explore the potential antidepressant effect of GPR55 agonist and electroacupuncture (EA), a common therapy for depression in China. Several behavioral tests i.e. forced swimming test, open field test and elevated plus maze were performed to evaluate the depression- and anxiety-like behaviors in mice. Expression of GPR55, hippocampal neuroinflammation, and neurogenesis were detected using immunohistochemistry, western blot and RT-PCR. Then, the effect of a GPR55 agonist, O-1602 on depression- and anxiety-like behaviors as well as hippocampal neuroinflammation and neurogenesis was examined. Furthermore, the potential antidepressant effect of 3-week EA treatment was also evaluated in another independent experiment. In the experiment, the behaviors and hippocampal neuroinflammation and neurogenesis were also subsequently examined.ResultsAfter CSDS, the protein level of GPR55 was decreased only in susceptible mice but the mRNA expression was not significantly different in all CSDS mice. Additionally, depression- and anxiety-like behaviors are accompanied by neuroinflammation and reduced neurogenesis in the hippocampus. And the activation of GPR55 during the process of CSDS prevented the development of depression- and anxiety- like behaviors, as well as hippocampal neuroinflammation and neurogenetic damage. Similarly, EA alleviated the depression- and anxiety-like behaviors, hippocampal neuroinflammation, and neurogenetic damage as well as decreased protein level of GPR55 in hippocampus induced by CSDS.ConclusionsOur research demonstrated that activation of hippocampal GPR55 could rescue depression and anxiety phenotypes, reduce hippocampal neuroinflammation, and enhance hippocampal neurogenesis. Moreover, GPR55 might be involved in the beneficial effect of EA on depression.