Brain and Muscle Energy Group – University of Copenhagen

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Projects in Brain and Muscle Energy Group

Professor Bergersen’s research is focused on function, regulation and transport of lactate and other monocarboxylates in the brain in young and old animals and humans. Bergersen discovered that a G-protein coupled lactate receptor (GPR81 or HCAR1) is present and active in brain (Lauritzen KH et al. 2014 Cereb Cortex; Morland C et al. 2015 J Neurosci Res). She then showed that HCAR1 mediates effects of physical exercise on the brain (Morland C et al. 2017 Nat Commun): after high intensity interval exercise 5 days weekly for 7 weeks the combined neurotrophic / angiotrophic growth factor VEGF and the capillary density increased in hippocampus. The effects were mimicked by injections of lactate. The effects of both exercise and lactate were absent in HCAR1 knockout mice, showing, for the first time, that a substance –lactate– released in high quantities by exercising muscle causes supportive effects in brain through an identified receptor.

This work on HCAR1 took place in Oslo with co-authors from CEHA (Holm-Hansen, Gjedde, Diget). Further research at CEHA III is focused on delineating the mechanistic basis and translation potential of these discoveries. This includes work by Bergersen’s PhD students, EH Diget, with the group of TW Schwartz on G-protein receptors, and ØP Haugen, with CEHA Managing Director LJ Rasmussen on HCAR1 modulation of glycolytic and mitochondrial functions of pancreatic cancer cells. Haugen is the recipient of an Erasmus+ traineeship at CEHA.

One potential area of HCAR1 targeted therapy is against cerebral malaria, as discussed in a perspective article co-authored with Kolko, Gjedde and Bergersen’s postdoc Mariga (Mariga S et al. 2014 Front Neurosci). This project is part of a partnership started to fight poverty-related diseases in Africa. 

Bergersen’s PhD student S Ulrik Holm (born Holm-Hansen), collaborating with T Karl in Sidney on a Lundbeck Foundation fellowship, showed that a high fat diet alleviated impaired social recognition memory in a mouse model of schizophrenia (Holm-Hansen S et al. 2016 Genes Brain Behav). Other work, with V Bohr and M Scheibye-Knudsen, explored the effects of high fat diets in mouse models of aging and mtDNA damage (Scheibye-Knudsen M et al. 2014 Cell Metab; Lauritzen KH et al. 2016 Neurobiol Aging).

Bergensen and students also work with LJ Rasmussen and M Lauritzen to characterize changes at neural synapses and in mitochondria in DNA repair-deficient transgenic mice (Lauritzen KH et al. 2015 Am J Physiol Heart Circ Physiol; Fakouri NB et al. 2017 Sci Rep; Thomsen K et al. 2018 Neurobiol Aging). 

She collaborates with M Kolko’s group to decipher mechanisms of lactate and glutamate in the retina (Skytt D 2016 Biomed Res Int; Kolko M et al. 2016 Neurochem Res; Vohra R et al. 2017 Mitochondrion).