Adult hippocampal neurogenesis inversely correlates with microglia in conditions of voluntary running and aging

Elias Gebara,Nicolas Toni,Jacqueline Kocher-Braissant,Sebastien Sultan

doi:10.3389/fnins.2013.00145

Abstract

Adult hippocampal neurogenesis results in the formation of new neurons and is a process of brain plasticity involved in learning and memory. The proliferation of adult neural stem or progenitor cells is regulated by several extrinsic factors such as experience, disease or aging and intrinsic factors originating from the neurogenic niche. Microglia is very abundant in the dentate gyrus (DG) and increasing evidence indicates that these cells mediate the inflammation-induced reduction in neurogenesis. However, the role of microglia in neurogenesis in physiological conditions remains poorly understood. In this study, we monitored microglia and the proliferation of adult hippocampal stem/progenitor cells in physiological conditions known to increase or decrease adult neurogenesis, voluntary running and aging respectively. We found that the number of microglia in the DG was strongly inversely correlated with the number of stem/progenitor cells and cell proliferation in the granule cell layer. Accordingly, co-cultures of decreasing neural progenitor/glia ratio showed that microglia but not astroglia reduced the number of progenitor cells. Together, these results suggest that microglia inhibits the proliferation of neural stem/progenitor cells despite the absence of inflammatory stimulus.

Highlights

In the mammalian brain, adult neural stem cells reside in the subventricular zone and subgranular zone (SGZ) of the hippocampus and continue to produce new neurons throughout life (Altman, 1969)
These results indicate that the density of proliferative cells, cell proliferation and the density of immature neurons decreased with aging and increased with voluntary running
In this study, we exploited the physiological variations of adult neurogenesis induced by voluntary running and aging to examine the correlation between microglia and adult hippocampal neurogenesis in absence of inflammatory stimulus

Summary

Introduction

Adult neural stem cells reside in the subventricular zone and subgranular zone (SGZ) of the hippocampus and continue to produce new neurons throughout life (Altman, 1969). The neurogenic niche is constituted by stem cells and their progenies, astrocytes, oligodendrocytes, endothelial cells, microglia, mature and immature neurons (Shihabuddin et al, 2000; Song et al, 2002; Zhao et al, 2008; Bonaguidi et al, 2011). These cells release a wide array of factors that control adult neurogenesis. The contribution of specific cell types on the processes of adult neurogenesis remains poorly determined

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