GH Mediates Exercise-Dependent Activation of SVZ Neural Precursor Cells in Aged Mice

Daniel G. Blackmore,Perry F. Bartlett,Michael J. Waters,Jana Vukovic,Eva Mezey

doi:10.1371/journal.pone.0049912

Abstract

Here we demonstrate, both in vivo and in vitro, that growth hormone (GH) mediates precursor cell activation in the subventricular zone (SVZ) of the aged (12-month-old) brain following exercise, and that GH signaling stimulates precursor activation to a similar extent to exercise. Our results reveal that both addition of GH in culture and direct intracerebroventricular infusion of GH stimulate neural precursor cells in the aged brain. In contrast, no increase in neurosphere numbers was observed in GH receptor null animals following exercise. Continuous infusion of a GH antagonist into the lateral ventricle of wild-type animals completely abolished the exercise-induced increase in neural precursor cell number. Given that the aged brain does not recover well after injury, we investigated the direct effect of exercise and GH on neural precursor cell activation following irradiation. This revealed that physical exercise as well as infusion of GH promoted repopulation of neural precursor cells in irradiated aged animals. Conversely, infusion of a GH antagonist during exercise prevented recovery of precursor cells in the SVZ following irradiation.

Highlights

The subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus of the hippocampus are the two niches in the brain where neurogenesis occurs throughout adulthood
We investigated the effect of locally targeting growth hormone (GH) signaling by infusing the competitive GH antagonist G120R into the lateral ventricle of aged WT mice during the 21-day exercise period
In the present study we have demonstrated that GH mediates the activation of neural precursor cell (NPC) within the SVZ of aged mice after exercise

Summary

Introduction

The subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus of the hippocampus are the two niches in the brain where neurogenesis occurs throughout adulthood. The production of new neural cells has been shown to decline with age in both the SVZ [1,2] and the hippocampus [3]. Voluntary exercise has been reported to stimulate neurogenesis [4,5] and counteract the natural decline in neural precursor number [6,7] within the hippocampus of aged animals. Hippocampal neurogenesis has been shown to occur post-exercise, this appears not to be the case for the SVZ [8]. Using the neurosphere assay [9], we have previously observed increases in precursor cell activation within the SVZ of the aged brain after physical exercise [2]. Despite numerous studies the mechanism by which this neural precursor activation occurs is still to be fully elucidated

Methods

Results

Conclusion