Age Associated Increase in Microglia Inflammation and Phagocytosis in the Adult Neural Stem Cell Niche.

Abstract

Neurogenesis occurs throughout life but is reduced aging. We show that during aging, microglia in the Subventricular Zone become activated and display an inflammatory phenotype. We show that young SVZ microglia have reduced phagocytic capacity compared to whole brain microglia in vitro, suggesting that these niche microglia are specialized not to phagocytize stem cells and progenitors. However, during aging, SVZ microglia exhibit increased phagocytosis. We show that during aging, there is a significant increase in the number of microglia that have NSC and progenitor markers within the lysosomes, strongly suggesting that during aging microglia engulf NSCs and progenitors. Reducing inflammation improves proliferation but had no significant reduction on phagocytosis suggesting that inflammation is not a key driver in the age-associated phagocytosis but is important in reduced proliferation. This indicates that SVZ microglia are key regulators of neurogenesis in the aged SVZ.