The final frontier: Transient microglia reduction after cosmic radiation exposure mitigates cognitive impairments and modulates phagocytic activity

Abstract

Microglia are the primary immune element within the brain, which are responsible for monitoring synapse function and neuron health. Exposure to cosmic radiation has the potential to cause long-term cognitive deficits in rodent models and therefore indicates a difficult challenge for future astronauts piloting interplanetary travel. Here, we discuss the potential of transient microglia depletion after the injury to ameliorate the harsh microenvironment of the brain and eliminate any potential long-term cognitive effects. Repopulation of microglia enables phagocytic phenotypes to be circumvented, via the reduction of Phagocytic and lysosomal markers, potentially being responsible for increased neuroprotection. Brief depletion of microglia after irradiation mitigated the development of any long-term memory deficits, comparable to healthy animals. Chronically, microglial levels were not affected by cosmic radiation followed by temporary microglia depletion. Following repopulation, improved recognition memory was paralleled by downregulated complement receptor C5aR. Preserved synapse function also demonstrated the therapeutic ability of microglia depletion as it corresponded with fewer phagocytic microglia phenotypes. The understanding of long-term radiation-induced cognitive impairments is vital for the protection of future astronauts and equally as important for current cancer patients. Temporary microglia depletion showed promise in preventing any deleterious cognitive impairments following exposure to elements of cosmic radiation, such as helium and high-charge nuclei.

Keywords: Galactic cosmic ray; microglia; radiation; sex dimorphism; synapse.