VEGF is necessary for exercise‐induced adult hippocampal neurogenesis

TLDR

Declining learning and memory function is linked to reduced adult hippocampal neurogenesis, a process that is suppressed by chronic stress or depression but markedly enhanced by voluntary exercise despite elevated stress hormones. The study examined how running signals the brain and identified peripheral vascular endothelial growth factor (VEGF) as essential for exercise‑induced neurogenesis. Blocking VEGF eliminated the neurogenic effect of running without affecting baseline neurogenesis, indicating that VEGF acts as a somatic regulator of adult hippocampal neurogenesis independent of central pathways.

Abstract

Abstract Declining learning and memory function is associated with the attenuation of adult hippocampal neurogenesis. As in humans, chronic stress or depression in animals is accompanied by hippocampal dysfunction, and neurogenesis is correspondingly down regulated, in part, by the activity of the hypothalamic–pituitary–adrenal axis as well as glutamatergic and serotonergic networks. Antidepressants can reverse this effect over time but one of the most clinically effective moderators of stress or depression and robust stimulators of neurogenesis is simple voluntary physical exercise such as running. Curiously, running also elevates circulating stress hormone levels yet neurogenesis is doubled in running animals. In evaluating the signalling that running provides to the central nervous system in mice, we have found that peripheral vascular endothelial growth factor (VEGF) is necessary for the effects of running on adult hippocampal neurogenesis. Peripheral blockade of VEGF abolished running‐induced neurogenesis but had no detectable effect on baseline neurogenesis in non‐running animals. These data suggest that VEGF is an important element of a ‘somatic regulator’ of adult neurogenesis and that these somatic signalling networks can function independently of the central regulatory networks that are typically considered in the context of hippocampal neurogenesis.