The role of convergent ion channel pathways in microglial phenotypes: a systematic review of the implications for neurological and psychiatric disorders

Increases in the activated state of microglia, the main neuroimmune cells, are widely reported in the brains of patients with neurological and psychiatric disorders. Microglia transform from the resting to the activated state by sensing their environment, aided by a variety of ion channels. To examine the effect of ion channels on microglial phenotypes, we conducted a systematic review of immunohistochemical analyses of these neuroimmune cells in animal models following administration of ion channel antagonists, compared to control conditions. A systematic search of the PubMed and Web of Science electronic databases using the PRISMA and WHO methodologies for systematic reviews yielded 15 original peer-reviewed studies. The majority (13 out of 15) of these studies reported a decrease in microglial activated state after ion signaling pharmacological blockade. The studies provide evidence that acute administration of ion channel antagonists leads to a reduction in microglial activation in rodent brains in the models for epilepsy, Parkinson’s disease, inflammation, pain, ischemia, and brain and spinal cord injury. Future research should explore microglial-specific druggable targets for neurological and psychiatric disorders. The investigation of acute and chronic administration of ion channel antagonists in microglial phenotypes in primates and the development of microglia-like cells derived from human stem cells could be valuable sources in this direction.