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Brain and Muscle Energy group

The research group investigate the role of lactate in pathogenic brain as we age.

Old people walking

"Exercise your heart and it will benefit your brain"

Photo: Colourbox

Why is physical exercise good for the brain?

In numerous investigations, physical exercise is the most effective measure against dementia, and is beneficial against normal aging and several brain diseases; how does information from muscles reach the brain? We just found out:

Active muscles deliver large quantities of lactate to the blood and thereby to the brain, where it hits a receptor protein, the lactate receptor HCAR1. The activated HCAR1 causes production of growth factors, such as VEGF, which stimulates nerve cells and causes formation of new capillaries – the thinnest blood vessels, where the vital substance exchange takes place. Seven weeks of high intensity interval training five days a week, or injections of lactate to reach similar blood lactate levels, caused increase of VEGF and capillaries in hippocampus in wild-type mice, but not in knockout mice lacking HCAR1.

This is the first time that a substance from exercising muscle has been shown to change the brain through an identified receptor. As impaired blood supply and nerve cell death are key problems in aging and neurodegenerative diseases, including Alzheimer’s disease, the findings open a new approach to treatment.

Projects

Roles of the HCAR1 in brain

Under the Research Council of Noway sponsored Project number 214458 "How does physical exercise translate into better brains?" we discovered that the lactate receptor HCAR1 is expressed and active in brain (Lauritzen KH et al 2014 Cereb Cortex) and now present the first demonstration of a physiological role of this receptor in the living brain (Morland C, Andersson KA et al 2017 Nat Commun twice): HCAR1 mediates an exercise induced increase in the neuro-vasculo-trophic growth factor VEGF and in capillary density in brain (Figure 1).

The exercise effect was reproduced by injection of lactate to achieve similar blood lactate levels. The effects were abolished in knockout mice lacking HCAR1. The change in VEGF and capillary density comprised the dentate hilus of hippocampus known to undergo adult neurogenesis induced by exercise. In cerebellum the same wild-type mice showed no significant change in VEGF or capillary density.

The localization of HCAR1 was revealed in mRFP-HCAR1 reporter mice expressing monomeric red fluorescent protein under the HCAR1 promoter (Figure 2). It turned out to be very highly concentrated in pial cells adjacent to the blood vessels supplying the brain, in their course in the pia mater, and accompanying the vessels as they penetrate into the brain parenchyma, partly expressing pericyte markers such as platelet-derived growth factor receptor β (PDGFRβ). This means that HCAR1 is at a strategic site for monitoring entry and exit of lactate in brain, for influencing brain blood flow and drainage of brain extracellular fluid.

HCAR1: New deal for Dementia

Under Nasjonalforeningen for folkehelsen, sponsored Project number 461516 "Lactate receptor HCAR1: New deal for Dementia", the research group has started up a new project. The project will run from 2018 to 2020.

Cooperation

We currently have collaborations including the labs of:

Tags: Lactate receptor, HCAR1, Physical activity and brain function, VEGF, BDNF, neurogenesis, angiogenesis
Published Aug. 9, 2018 2:41 PM - Last modified Feb. 22, 2021 6:39 PM

Contact

Institute of Oral Biology
Domus Odontologica
Sognsvannsveien 10
0372 Oslo

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