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Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1

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  • Cecilie Morland

    (The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
    Institute for Behavioral Sciences, Faculty of Health Sciences, Oslo and Akershus University College
    The Synaptic Neurochemistry Lab, Institute of Basic Medical Sciences, Healthy Brain Ageing Centre, University of Oslo)

  • Krister A. Andersson

    (The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
    Institute for Behavioral Sciences, Faculty of Health Sciences, Oslo and Akershus University College
    The Synaptic Neurochemistry Lab, Institute of Basic Medical Sciences, Healthy Brain Ageing Centre, 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
    Institute for Behavioral Sciences, Faculty of Health Sciences, Oslo and Akershus University College
    The Synaptic Neurochemistry Lab, Institute of Basic Medical Sciences, Healthy Brain Ageing Centre, University of Oslo)

  • Liv Kleppa

    (The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
    The Synaptic Neurochemistry Lab, Institute of Basic Medical Sciences, Healthy Brain Ageing Centre, 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
    The Synaptic Neurochemistry Lab, Institute of Basic Medical Sciences, Healthy Brain Ageing Centre, 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
    Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen)

  • Lauritz H. Kennedy

    (The Brain and Muscle Energy Group, Electron Microscopy Laboratory, University of Oslo
    The Synaptic Neurochemistry Lab, Institute of Basic Medical Sciences, Healthy Brain Ageing Centre, 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
    The Synaptic Neurochemistry Lab, Institute of Basic Medical Sciences, Healthy Brain Ageing Centre, University of Oslo
    Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen)

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.

Suggested Citation

  • 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 & Eivi, 2017. "Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1," Nature Communications, Nature, vol. 8(1), pages 1-9, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15557
    DOI: 10.1038/ncomms15557
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    Cited by:

    1. Xue Fan Wang & Robin Vigouroux & Michal Syonov & Yuriy Baglaenko & Angeliki M. Nikolakopoulou & Dene Ringuette & Horea Rus & Peter V. DiStefano & Suzie Dufour & Alireza P. Shabanzadeh & Seunggi Lee & , 2024. "The liver and muscle secreted HFE2-protein maintains central nervous system blood vessel integrity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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