Microglial sex differences in innate high anxiety and modulatory effects of minocycline

We report striking sex differences, especially in the major microglia clusters of HABs, indicating a higher expression of genes associated with phagocytosis and synaptic engulfment in the female compared to the male. On a functional level, we show that female HAB microglia engulf a greater amount of hippocampal vGLUT1+ excitatory synapses compared to the male. We moreover showed that female HAB microglia engulf more synaptosomes compared to the male HAB in vitro. Due to previously reported effects of minocycline on microglia, we finally administered oral minocycline to HABs of both sexes and showed a significant reduction in the engulfment of synapses by female HAB microglia. In parallel to our microglia-specific findings, we further showed an anxiolytic effect of minocycline on female HABs, which is complementary to our previous findings in the male HABs. Our study, therefore, identifies the altered function of synaptic engulfment by microglia as a potential avenue to target and resolves microglia heterogeneity in mice with innate high anxiety.PMID:38552926 | DOI:10.1016/j.bbi.2024.03.035
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Source Type: research