Electronic Poster | Session 2
005 – Microglial Repopulation Attenuates Age-Associated Dysfunction Independent of Neuroinflammation
Shane O’Neil (1) – Emma Hans (1) – Starr Jiang (1) – Andrew Perl (1) – Jonathan Godbout (1, 2, 3)
Department of Neuroscience, The Ohio State University, Columbus, United States (1) – Department of Neuroscience (2) – Institute for Behavioral Medicine Research (3) – Chronic Brain Injury Program, The Ohio State University
Microglia are the resident innate immune cells of the central nervous system. Limited turnover throughout the lifespan leaves microglia susceptible to age-associated dysfunction. Indeed, we and others have reported microglia develop a pro-inflammatory, or “primed,” profile with age, characterized by increased expression of inflammatory mediators. However, we have recently shown replacement of aged microglia with new cells does not attenuate this hyper-inflammatory phenotype. Microglial repopulation in aged mice using the CSF1R antagonist PLX5622 does, however, result in new microglia with decreased lipofuscin and CD68 expression. Lipofuscin is a source of reactive oxygen species (ROS) and causes metabolic dysfunction in a cell. Therefore, we hypothesized microglial repopulation in aged mice would result in an attenuation of age-associated ROS buildup and phagocytic dysfunction. Here we provide novel data showing microglial repopulation in aged mice decreases ROS content in aged microglia but does not reverse age-associated deficits in microglial phagocytosis. Moreover, microglial repopulation attenuated learning and memory deficits in aged mice. Taken together, these data show microglial repopulation in aged mice results in cells with significantly lower levels of CD68, lipofuscin, and ROS, as well as attenuating learning and memory deficits, despite a continuing pro-inflammatory phenotype.