Recent studies suggest that peripheral inflammation, often seen during sickness, contributes to the onset of depression. An immediate response to infection typically induces behavioral changes characterized by decreased appetite and mobility, defined as sickness behaviors in this study. Following this response, depressive-like behavior, characterized by behavioral despair, may emerge and can persist. However, the mechanism through which sickness triggers depressive-like behavior remains unknown.
Microglia, the resident macrophages in the CNS, respond to inflammatory signals from the periphery and modulate neuronal activity. Here, we tested whether microglia contribute to the induction of depressive-like behavior post-inflammation. 
To examine changes in microglia, we utilized a model of systemic inflammation in rodents through lipopolysaccharide (LPS) injection. Subsequent behavioral assays in mice validated the onset of both sickness and depressive-like behavior. Moreover, both the elimination of microglia and functional modulation through the use of PLX3397 and minocycline respectively, prevented the development of depressive-like, but not sickness behavior.
Taken together, our findings suggest that microglia are essential intermediates for the development of depressive-like, but not sickness behavior.