With our discovery that lactate, acting through its receptor HCAR1, can mimic high intensity exercise to increase capillary density and the combined neurotrophic-angiotrophic growth factor VEGF, as well as adult neurogenesis, in brain. We now target HCAR1 pharmacologically for potential treatment and prophylaxis of dementias
In 2001 we discovered that the monocarboxylate transporter 2 (MCT2) to be expressed in excitatory synapses at the postsynaptic density of spines in vivo in the brain (Bergersen et al., 2001). MCT2 is important for Long Term Potentiation. We have also discovered that the different impulse pattern for different skeletal muscle fibers decides which type of monocarboxylate transporters to be expressed (Bergersen et al., 2006). Later the discovery of HCAR1 (GPR81) (Lauritzen KH Cerebral Cortex 2014) to be present and function in the brain opened a new field of treatment for brain pathology. Our group have shown that lactate injection can mimic high intensity interval training resulting in new blood vessels and new nerve cells in the brain (Morland C et al., 2017 Nature Communication; Lambertus M et al., Acta Physiologica 2021).
Morland C, Andersson KA, Haugen ØP, Hadzic A, Kleppa L, Gille A, Rinholm JE, Palibrk V, Diget EH, Kennedy LH, Stølen T, Hennestad E, Moldestad O, Cai Y, Puchades M, Offermanns S, Vervaeke K, Bjørås M, Wisløff U, Storm-Mathisen J, Bergersen LH (2017) Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1 Nat Commun doi: 10.1038/ncomms15557.
Lauritzen KH, Hasan-Olive MM, Regnell CE, Liv Kleppa, Scheibye-Knudsen M, Gjedde A, Klungland A, Bohr V, Storm-Mathisen J, Bergersen LH (2016) A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain. Neurobiol Aging
Gundersen V, Storm-Mathisen J, Bergersen LH (2015) Neuroglial Transmission. Physiol Rev 95(3):695-726.
Lauritzen KH, Kleppa L, Aronsen JM, Eide L, Carlsen H, Haugen ØP, Sjaastad I, Klungland A, Rasmussen LJ, Attramadal H, Storm-Mathisen J, Bergersen LH (2015) Impaired dynamics and function of mitochondria caused by mtDNA toxicity leads to heart failure. Am J Physiol Heart Circ Physiol 309(3):H434-49.
Bergersen LH (2015) Lactate transport and signaling in the brain: potential therapeutic targets and roles in body-brain interaction. J Cereb Blood Flow Metab 35(2):176-185.