Poster abstracts

Poster number 98 submitted by Lars Nelson

Sex differences in microglial phagocytosis and support of neurogenesis in the neonatal hippocampus

Lars H. Nelson (Neuroscience Graduate Program), Spencer Warden (Department of Neuroscience, The Ohio State University), Pavan Peketi (Department of Neuroscience, The Ohio State University), Kathryn M. Lenz (Department of Neuroscience and Psychology, The Ohio State University)

Abstract:
Microglia are the innate immune cell of the central nervous system and are important for many developmental functions. Microglia eat and digest synapses and cells in a process called phagocytosis, and stimulate neurogenesis and synapse formation by secreting diffusible factors. Interestingly, many of these same functions also show sex differences throughout the brain and microglia show sex differences in morphology throughout the brain. We focused on the hippocampus, where males have more neurogenesis during the early neonatal period compared to females, and sought to determine whether microglia regulate neurogenesis in a sex-specific manner. We found that there were significantly more phagocytic microglia in females compared to males during the critical period for sexual differentiation, and estradiol decreased the number of phagocytic microglia in females to male levels. We also found that females have more phagocytic microglia expressing the lysosomal marker CD68+ confirming the sex difference in phagocytosis, and that female microglia phagocytize more non-pyknotic and progenitor cells, but not recently-divided or pyknotic cells. To determine the molecular mechanisms by which microglia phagocytize cells we assayed gene expression of several microglia-specific phagocytic genes in the hippocampus and found that females had higher expression of several such genes, including CD68, Cybb, Tyrobp, and Trem2. Next, to determine whether microglia support the sex difference in neurogenesis in the neonatal hippocampus, we used liposomal clodronate to deplete microglia. Depleting microglia in neonatal hippocampus decreased cell proliferation in males, but not females. We are currently assaying microglial genes that support neurogenesis. Future studies will test whether sex differences in microglial genes involved in phagocytosis and support of neurogenesis are programmed by estradiol. These studies show sex differences in several microglia functions that are important for normal brain development that may lead to sex differences in brain function under basal conditions or following stress or inflammation.

Keywords: Microglia, Brain development, Sex differences