Microglia as a Potential Target for Antidepressant: A Systematic Review on Preclinical studies

Depression is a heterogeneous disorder with more than one possible etiologies. Currently, studies are mostly focused on neuronal dysfunction, while the involvement of other brain cells, such as microglia, has not been widely explored. This review aimed to systematically review the studies reporting the effect of microglia inhibitors on depressive-like behavior in rodent models, to obtained a better understanding of the effectiveness of the intervention against depression. The PubMed database was explored from January 2011 to April 2021 with related keywords for full-text publications reporting antidepressant effects of microglial inhibitor in rodents. We identified 713 research publications, of which only 25 studies met the inclusion criteria and were included for analysis. Administration of antidepressant drugs/compounds that inhibit microglia was reported to be beneficial because it improved depression-like symptoms by reducing outcomes based on immobility, anhedonia, and locomotor activity. Microglia inactivation has been reported to occur through inhibition of the HMGB1/TLR4/NF-B and NLRP3/NF-κB pathways, as well as improved communication of microglia neurons through increased interaction of CX3CL1 with CX3CR1. These data indicated that the use of an agent inhibiting microglia activity is promising as a strategy in overcoming depression in humans.