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Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1

Morland, Cecilie ; Andersson, Krister A ; Haugen, Øyvind P ; Hadzic, Alena ; Kleppa, Liv ; Gille, Andreas ; Rinholm, Johanne E ; Palibrk, Vuk ; Diget, Elisabeth H ; Kennedy, Lauritz H ; Stølen, Tomas ; Hennestad, Eivind ; Moldestad, Olve ; Cai, Yiqing ; Puchades, Maja ; Offermanns, Stefan ; Vervaeke, Koen ; Bjørås, Magnar ; Wisløff, Ulrik ; Storm-Mathisen, Jon ; Bergersen, Linda H

Nature communications, 2017-05, Vol.8 (1), p.15557-9, Article 15557 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1
Autor: Morland, Cecilie ; Andersson, Krister A ; Haugen, Øyvind P ; Hadzic, Alena ; Kleppa, Liv ; Gille, Andreas ; Rinholm, Johanne E ; Palibrk, Vuk ; Diget, Elisabeth H ; Kennedy, Lauritz H ; Stølen, Tomas ; Hennestad, Eivind ; Moldestad, Olve ; Cai, Yiqing ; Puchades, Maja ; Offermanns, Stefan ; Vervaeke, Koen ; Bjørås, Magnar ; Wisløff, Ulrik ; Storm-Mathisen, Jon ; Bergersen, Linda H
Assuntos: Animals ; Brain - blood supply ; Capillaries - cytology ; Capillaries - drug effects ; Capillaries - metabolism ; Injections, Subcutaneous ; Lactic Acid - administration & dosage ; Lactic Acid - blood ; Lactic Acid - metabolism ; Male ; Mice ; Mice, Knockout ; Models, Animal ; Muscle, Skeletal - blood supply ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Neovascularization, Physiologic - physiology ; Pericytes - metabolism ; Physical Conditioning, Animal - physiology ; Receptors, G-Protein-Coupled - genetics ; Receptors, G-Protein-Coupled - metabolism ; Vascular Endothelial Growth Factor A - metabolism
É parte de: Nature communications, 2017-05, Vol.8 (1), p.15557-9, Article 15557
Notas: These authors contributed equally to this work.
Descrição: 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.
Editor: England: Nature Publishing Group
Idioma: Inglês;Norueguês

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Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1

England: Nature Publishing Group

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