Effects of Fstl1 on neuroinflammation and microglia activation in lipopolysaccharide-induced acute depression-like mice.

Abstract

Depression is the most prevalent psychiatric illness, and its pathogenesis is associated with neuroinflammation. Follistatinlike protein 1 (FSTL1), a novel inflammatory protein, participates in the pathogenesis of diseases related to neuroinflammation. Therefore, we aimed to investigate the effect of FSTL1 in the pathogenesis of depression mediated using neuroinflammation-mediated models. Our results showed that lipopolysaccharide (LPS) administration could induce despair-like behavior and increase proinflammatory cytokine levels in both male and female mice. Then, a significant positive correlation between hippocampal Fstl1 mRNA expression, microglial activation and despair-like behaviors was observed in male mice. Moreover, knockdown FSTL1 significantly reduced microglial activation and the expression of proinflammatory cytokines, while overexpression of Fstl1 in hippocampus could exacerbate the activation of microglial under the LPS-induced condition in male mice. Mechanically, knockdown Fstl1 inhibited LPS-induced activation of BV2 microglia and reduced the production of proinflammatory cytokines, thereby protecting the survival of HT22 neurons. In conclusion, our results implied that Fstl1 may modulate despair-like behaviors through regulation of microglial activation and neuronal viability, which would lay the experimental and theoretical foundation for the neuroinflammatory mechanisms underlying depression.