BioProject

Maternal immune activation (MIA) during pregnancy has been linked to an increased risk in the offspring to develop schizophrenia. More...

Maternal immune activation (MIA) during pregnancy has been linked to an increased risk in the offspring to develop schizophrenia. In schizophrenic patients, a dysregulation of microglia, the brain's immune competent cells, was reported and treatment with the immunomodulatory compound minocycline proved to be beneficial. Nevertheless, it remains unclear how specific minocycline treatment acts on microglia cells in vivo. Utilizing a mouse model of schizophrenia triggered by a maternal injection of the viral mimic PolyI:C we performed mRNA-sequencing on freshly isolated microglia form adult PolyI:C mice with and without chronic minocycline treatment. In the adult offspring an altered microglial transcriptome associated with changes in cell activation, motility, adhesion and phagocytosis was accompanied by behavioral deficits. Treatment with 3mg/kg/day minocycline for 5 weeks restored the changes in microglial transcriptional signature and phagocytic activity while attenuating the behavioral deficits. Our findings indicate that maternal immune activation induces profound changes in microglial transcriptome and function in the adult offspring and minocycline represents a valuable drug to restore a normal cellular and functional phenotype. Less...