The dysfunction of parvalbumin interneurons mediated by microglia contributes to cognitive impairment induced by lipopolysaccharide challenge

Abstract

BackgroundThe mechanisms underlying cognitive impairments induced by systemic inflammation remain unclear. Increasing evidence has suggested that parvalbumin (PV) interneurons play an important role in regulating cognitive behaviors and its dysfunction is implicated in many neurological disorders. Thus, the present study was aimed to detect whether the destruction of PV interneurons mediates cognitive impairment associated with systemic inflammation. MethodsMale wild-type C57BL/6J mice (12–14 weeks old) received lipopolysaccharide (LPS 2 mg/kg i.p.) injection to establish the systemic inflammation model. For the suppression of microglial activation, minocycline (50 mg/kg i.p.) was applied. Animal behavior tests were conducted on day 3 post-LPS injection including the open field test, fear conditioning test and Y maze test. The PV expression in hippocampus was detected by Western blot and immunofluorescence. The number of perisomatic boutons around the NeuN–positive cells and microglia in hippocampus was detected by immunofluorescence. ResultsLPS induced hippocampus-dependent memory and working memory impairment, coinciding with decreased PV expression, reduced perisomatic boutons around the NeuN–positive cells and activated microglia in the hippocampus. Notably, the treatment of minocycline suppressed the microglial activation and rescued the PV expression as well as the perisomatic boutons around the NeuN–positive cells in the hippocampus, contributing to improved cognitive function. ConclusionOur study suggests that the dysfunction of parvalbumin interneurons mediated by microglia plays a key role in LPS-induced cognitive impairments, which may serve a therapeutic strategy for cognitive disorders associated with systemic inflammation.