Øyvind Pernell Haugen

• Haugen, Øyvind Pernell; Vallenari, Evan Michael; Belhaj, Imen; Småstuen, Milada Cvancarova; Storm-Mathisen, Jon; Bergersen, Linda Hildegard & Åmellem, Ingrid (2020). Blood lactate dynamics in awake and anaesthetized mice after intraperitoneal and subcutaneous injections of lactate—sex matters. PeerJ.  ISSN 2167-8359.  2020(1) . doi: 10.7717/peerj.8328 Fulltekst i vitenarkiv.
• Lambertus, Marvin; Øverberg, Linda Thøring; Andersson, Krister Andreas; Hjelden, Malin Sørli; Hadzic, Alena; Haugen, Øyvind Pernell; Storm-Mathisen, Jon; Bergersen, Linda Hildegard; Geiseler, Samuel & Morland, Cecilie (2020). L‐lactate induces neurogenesis in the mouse ventricular‐subventricular zone via the lactate receptor HCA1. Acta Physiologica.  ISSN 1748-1708. . doi: 10.1111/apha.13587 Fulltekst i vitenarkiv.
• Das, Mrinal Kumar; Furu, Kari; Evensen, Herman Sebastian Folkestad; Haugen, Øyvind Pernell & Haugen, Trine B. (2018). Knockdown of SPRY4 and SPRY4-IT1 inhibits cell growth and phosphorylation of Akt in human testicular germ cell tumours. Scientific Reports.  ISSN 2045-2322.  8(1), s 2462 . doi: 10.1038/s41598-018-20846-8 Fulltekst i vitenarkiv.
• Morland, Cecilie; Andersson, Krister; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv; Gille, Andreas; Rinholm, Johanne Egge; Palibrk, Vuk; Diget, Elisabeth Holm; Kennedy, Lauritz Hagen; Stølen, Tomas; Hennestad, Eivind; Moldestad, Olve; Cai, Yiqing; Puchades, Maja Amedjkouh; Offermanns, Stefan; Vervaeke, Koen Gerard Alois; Bjørås, Magnar; Wisløff, Ulrik; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2017). Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1. Nature Communications.  ISSN 2041-1723.  8 . doi: 10.1038/ncomms15557 Fulltekst i vitenarkiv. Vis sammendrag

  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. Editorial summary: Physical exercise promotes brain angiogenesis through an unknown signalling cascade. Morland et al. identify the elusive muscle-brain communication and show that lactate produced by muscle activity binds to its receptor HCAR1 in brain vessel-surrounding cells, stimulating VEGF production and brain angiogenesis.

• Lauritzen, Knut Husø; Kleppa, Liv; Aronsen, Jan Magnus; Eide, Lars; Carlsen, Harald; Haugen, Øyvind Pernell; Sjaastad, Ivar; Klungland, Arne; Rasmussen, Lene Juel; Attramadal, Håvard; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2015). Impaired dynamics and function of mitochondria caused by mtDNA toxicity leads to heart failure. American Journal of Physiology. Heart and Circulatory Physiology.  ISSN 0363-6135.  309(3), s H434- H449 . doi: 10.1152/ajpheart.00253.2014

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• Das, Mrinal Kumar; Furu, Kari; Evensen, Herman Sebastian Folkestad; Haugen, Øyvind Pernell & Haugen, Trine B. (2018). Roles for SPRY4 and SPRY4-IT1 in development of testicular germ cell tumour.
• Lambertus, Marvin; Sørli, Malin; Haugen, Øyvind Pernell; Andersson, Krister Andreas & Morland, Cecilie (2018). The effects of HCAR1 activation on the release of growth factors from pia mater fibroblasts.
• Øverberg, Linda Thøring; Andersson, Krister Andreas; Lambertus, Marvin; Hadzic, Alena; Haugen, Øyvind Pernell; Storm-Mathisen, Jon; Bergersen, Linda Hildegard & Morland, Cecilie (2018). Adult neurogenesis: A regulatory role of lactate through the lactate receptor HCAR1?.
• Andersson, Krister; Morland, Cecilie; Haugen, Øyvind Pernell; Bergersen, Linda Hildegard & Storm-Mathisen, Jon (2017). Physical exercise promotes brain angiogenesis through a lactate receptor. Vis sammendrag

  Physical exercise can improve brain function and delay neurodegeneration, but the initial signal from muscle to brain is unknown. Here we show that the lactate receptor (HCAR1) is highly enriched in fibroblast-like cells that line and surround the pial blood vessels supplying the brain, and that activation of HCAR1 stimulates vascular endothelial growth factor A (VEGFA) levels and angiogenesis in hippocampus. High intensity interval exercise (five days weekly for seven weeks), as well as L-lactate injected subcutaneously to similarly increase blood lactate levels, caused a substantial increase in brain VEGFA protein and microvessel density in wild-type mice, but not in knockout mice lacking HCAR1. In contrast, skeletal muscle showed no vascular HCAR1 expression and no HCAR1 dependent change in vascularization induced by exercise or lactate. To our knowledge, this is the first demonstration that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor.

• Andersson, Krister; Morland, Cecilie; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv; Gille, Andreas; Rinholm, Johanne Egge; Palibrk, Vuk; Diget, Elisabeth Holm; Kennedy, Lauritz Hagen; Stølen, Tomas; Hennestad, Eivind; Moldestad, Olve; Cai, Yiqing; Puchades, Maja; Offermanns, Stefan; Vervaeke, Koen; Bjørås, Magnar; Wisløff, Ulrik; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2017). Exercise benefits brain through the lactate receptor HCAR1, increasing VEGF and capillary density in hippocampus and cortex. Vis sammendrag

  While physical exercise is known to improve brain function and delay neurodegeneration, the signal from muscle to brain has not been identified. We show here that the lactate receptor, hydroxycarboxylic acid receptor 1 (HCAR1 also known as GPR81), mediates exercise induced increase in the content of vascular endothelial growth factor A (VEGFA) and in capillary density in the hippocampus and cerebral cortex. Mice were subjected to high intensity interval exercise 5 days per week for 7 weeks. Increases in VEGFA and capillary density were observed in wild-type (wt) mice, but not in knockout (ko) mice lacking HCAR1. Subcutaneous injections of L-lactate 5 days per week for 7 weeks, to achieve intermittently high blood lactate levels comparable to those after exercise, reproduced the findings in wt mice. No changes were observed in ko mice. The intermittent nature of the stimulation may be important since continuously high extracellular lactate has previously been observed to down-regulate HCAR1. To our knowledge, the present finding is the first demonstration that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor. No changes in VEGFA or capillary density were observed in the cerebellar cortex. HCAR1 was highly expressed in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in fibroblast-/pericyte-like cells along intracerebral microvessels. These cells are strategically placed to monitor changes in blood-born lactate as well as in brain extracellular lactate (which equilibrate across the vascular endothelium via monocarboxylate transporter 1). Skeletal muscle showed no vascular HCAR1 expression and no HCAR1-dependent change in vascularization induced by exercise or lactate. As VEGFA governs neuronal functions such as LTP as well as vascular growth, the increases may have direct effects on neurons as well as indirect effects through enhancement of vascularization. Both disturbed vascularization and impaired synaptic function are components of the pathogenesis in neurodegenerative dementias such as Alzheimer’s disease. The lactate receptor HCAR1 may prove a useful nutraceutical target for intervention in persons at risk for dementia who are unable to exercise sufficiently to achieve optimal HCAR1 stimulation through rises in blood lactate.

• Hadzic, Alena; Andersson, Krister; Haugen, Øyvind Pernell; Storm-Mathisen, Jon; Stølen, Tomas; Wisløff, Ulrik; Bergersen, Linda Hildegard & Morland, Cecilie (2016). Lactate receptor HCAR1 mediates synaptic plasticity.
• Morland, Cecilie; Andersson, Krister; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv; Gille, Andreas; Rinholm, Johanne Egge; Diget, Elisabeth Holm; Kennedy, Lauritz Hagen; Stølen, Tomas; Hennestad, Eivind; Cai, Yiqing; Puchades, Maja Amedjkouh; Offermanns, Stefan; Vervaeke, Koen Gerard Alois; Wisløff, Ulrik; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2016). A novel mechanism for cerebral angiogenesis via lactate receptor HCAR1 at pial vessels.
• Morland, Cecilie; Andersson, Krister; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv; Gille, Andreas; Rinholm, Johanne Egge; Elisabeth, Holm Diget; Kennedy, Lauritz Hagen; Stølen, Tomas; Hennestad, Eivind; Cai, Yiqing; Puchades, Maja Amedjkouh; Offermanns, Stefan; Vervaeke, Koen Gerard Alois; Wisløff, Ulrik; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2016). Exercise induces cerebral angiogenesis via lactate receptor HCAR1 at pial vessels.
• Haugen, Øyvind Pernell (2015). Neurons and glutamate receptors.
• Haugen, Øyvind Pernell (2014). Does a dysfunctional heart alter excitatory synapses in the hippocampus?.
• Herning, Hilde; Haugen, Trine B.; Das, Mrinal Kumar; Witczak, Oliwia; Tefre, Toril; Haugen, Øyvind Pernell & Andersen, Jorunn Marie (2014). Celler snakker sammen. Hvilket språk bruker de?.

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