Partial overlap in the symptom profile induced by microglia activation and systemic inflammation

Abstract

Microglial activation is a common feature of neurological and inflammatory diseases and may contribute to some associated symptoms. However, methodological limitations have made it challenging to identify the specific symptoms and behavioral consequences of selective microglial activation. In this study, we examined the spectrum of symptoms elicited by acute chemogenetic activation of microglia in mice and compared them to those induced by endotoxin-driven systemic inflammation. Both interventions upregulated inflammatory gene expression in the brain, reduced voluntary wheel running, and decreased self-care. Systemic inflammation additionally caused anorexia, weight loss, reduced motivation to work for palatable food, and impaired motor performance in the rotarod test--effects not observed with chemogenetic microglial activation. By showing that acute microglial activation reproduces certain motivational aspects of the sickness response while sparing other functions, the findings might shed new light on the contribution of microglia to symptoms and behavioral alterations during disease.