Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1
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- Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1
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Physical exercise can improve brain function and delay neurodegeneration; however, the initial signal from muscle to brain is unknown. Here we show that the lactate receptor (HCAR1) is highly enriched in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in pericyte-like cells along intracerebral microvessels. Activation of HCAR1 enhances cerebral vascular endothelial growth factor A (VEGFA) and cerebral angiogenesis. High-intensity interval exercise (5 days weekly for 7 weeks), as well as L-lactate subcutaneous injection that leads to an increase in blood lactate levels similar to exercise, increases brain VEGFA protein and capillary density in wild-type mice, but not in knockout mice lacking HCAR1. In contrast, skeletal muscle shows no vascular HCAR1 expression and no HCAR1-dependent change in vascularization induced by exercise or lactate. Thus, we demonstrate that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor.
Originalsprog | Engelsk |
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Artikelnummer | 15557 |
Tidsskrift | Nature Communications |
Vol/bind | 8 |
Antal sider | 9 |
ISSN | 2041-1723 |
DOI | |
Status | Udgivet - 2017 |
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