Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1

Cecilie Morland (), Krister A. Andersson, Øyvind P. Haugen, Alena Hadzic, Liv Kleppa, Andreas Gille, Johanne E. Rinholm, Vuk Palibrk, Elisabeth H. Diget, Lauritz H. Kennedy, Tomas Stølen, Eivind Hennestad, Olve Moldestad, Yiqing Cai, Maja Puchades, Stefan Offermanns, Koen Vervaeke, Magnar Bjørås, Ulrik Wisløff, Jon Storm-Mathisen and Linda H. Bergersen ()
Additional contact information
Cecilie Morland: The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
Krister A. Andersson: The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
Øyvind P. Haugen: The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
Alena Hadzic: The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
Liv Kleppa: The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
Andreas Gille: Institute for Experimental and Clinical Pharmacology and Toxicology, Mannheim Medical Faculty, Heidelberg University
Johanne E. Rinholm: The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
Vuk Palibrk: Norwegian University of Science and Technology
Elisabeth H. Diget: The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
Lauritz H. Kennedy: The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
Tomas Stølen: K.G. Jebsen Center of Exercise in Medicine, Norwegian University of Science and Technology
Eivind Hennestad: Laboratory of Neural Computation, University of Oslo
Olve Moldestad: Centre for Rare Disorders, Oslo University Hospital, Rikshospitalet
Yiqing Cai: The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
Maja Puchades: The Synaptic Neurochemistry Lab, Institute of Basic Medical Sciences, Healthy Brain Ageing Centre, University of Oslo
Stefan Offermanns: Max-Planck-Institute for Heart and Lung Research
Koen Vervaeke: Laboratory of Neural Computation, University of Oslo
Magnar Bjørås: Norwegian University of Science and Technology
Ulrik Wisløff: K.G. Jebsen Center of Exercise in Medicine, Norwegian University of Science and Technology
Jon Storm-Mathisen: The Synaptic Neurochemistry Lab, Institute of Basic Medical Sciences, Healthy Brain Ageing Centre, University of Oslo
Linda H. Bergersen: The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms15557

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