Linda Hildegard Bergersen

• Wang, He-Ling; Siow, Richard; Schmauck-Medina, Tomas; Zhang, Jianying; Sandset, Per Morten & Filshie, Clare [Vis alle 38 forfattere av denne artikkelen] (2024). Meeting Summary of The NYO3 5th NO-Age/AD Meeting and the 1st Norway-UK Joint Meeting on Aging and Dementia: Recent Progress on the Mechanisms and Interventional Strategies. The journals of gerontology. Series A, Biological sciences and medical sciences. ISSN 1079-5006. 79(4). doi: 10.1093/gerona/glae029.
• Pietilä, Riikka; Del Gaudio, Francesca; He, Liqun; Vázquez-Liébanas, Elisa; Vanlandewijck, Michael & Muhl, Lars [Vis alle 33 forfattere av denne artikkelen] (2023). Molecular anatomy of adult mouse leptomeninges. Neuron. ISSN 0896-6273. 111, s. 3745–3764. doi: 10.1016/j.neuron.2023.09.002. Fulltekst i vitenarkiv
• Norevik, Cecilie Skarstad; Huuha, Aleksi Matias; Røsbjørgen, Ragnhild; Bergersen, Linda Hildegard; Jacobsen, Kamilla & Miguel dos Santos, Rodrigo [Vis alle 13 forfattere av denne artikkelen] (2023). Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain. Journal of Sport and Health Science. ISSN 2095-2546. doi: 10.1016/j.jshs.2023.07.003. Fulltekst i vitenarkiv
• Vohra, Rupali; Sanz-Morello, Berta; Tams, Anna Luna Mølgaard; Mouhammad, Zaynab Ahmad; Freude, Kristine Karla & Hannibal, Jens [Vis alle 9 forfattere av denne artikkelen] (2022). Prevention of Cell Death by Activation of Hydroxycarboxylic Acid Receptor 1 (GPR81) in Retinal Explants. Cells. ISSN 2073-4409. 11(13). doi: 10.3390/cells11132098. Fulltekst i vitenarkiv
• Kennedy, Lauritz Hagen; Glesaaen, Emilie Rylund; Palibrk, Vuk; Pannone, Marco; Wang, Wei & Al-Jabri, Ali [Vis alle 13 forfattere av denne artikkelen] (2022). Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia. eLIFE. ISSN 2050-084X. 11. doi: 10.7554/eLife.76451. Fulltekst i vitenarkiv
• Haugen, Øyvind Pernell; Khuu, Cuong; Weidemann, Hanne Margrete; Utheim, Tor Paaske & Bergersen, Linda Hildegard (2022). Transcriptomic and functional studies reveal miR-431-5p as a tumour suppressor in pancreatic ductal adenocarcinoma cells. Gene. ISSN 0378-1119. 822. doi: 10.1016/j.gene.2022.146346. Fulltekst i vitenarkiv Vis sammendrag

  The lactate receptor HCAR1 (hydroxycarboxylic acid receptor 1) is highly expressed in pancreatic ductal adenocarcinoma (PDAC), where it regulates lactate transport between the cancer cells. Little is known about the underlying cause of high HCAR1 expression in PDAC, and in the present study, we investigated whether HCAR1 could be a target of miRNA regulation. By searching for predicted miRNA candidates in silico, we identified miR-431-5p as a possible regulator of HCAR1. We found miR-431-5p to repress HCAR1 expression through direct binding to the 3′ UTR. The endogenous expression of miR-431-5p and HCAR1 was found to be negatively related in the PDAC cell lines BxPC-3, Capan-2, and PANC-1. Overexpression of miR-431-5p inhibited cell proliferation in all the cell lines, and a shift in cell cycle progression and induction of apoptosis were found in the BxPC-3 cells. Transcriptomic analysis of mRNA from BxPC-3 cells revealed numerous differentially expressed genes (DEGs), including HCAR1, in response to miR-431-5p overexpression. A significant proportion of these DEGs was enriched in cancer-related processes and signalling pathways. Among the most significantly repressed DEGs was ATP6V0E1, encoding the integral subunit e of vacuolar ATPase (V-ATPase), an enzyme that is important for cancer cell survival. Small interfering RNA (siRNA)-mediated knockdown of HCAR1 and ATP6V0E1 showed that only knockdown of ATP6V0E1 mimicked the effect of miR-431-5p overexpression on cell viability. Our findings indicate that miR-431-5p acts as a tumour suppressor in PDAC cells, with BxPC-3 cells being most responsive.

• Lauritzen, Knut H.; Olsen, Maria Belland; Ahmed, Mohammed Shakil; Yang, Kuan; Rinholm, Johanne Egge & Bergersen, Linda H. [Vis alle 13 forfattere av denne artikkelen] (2021). Instability in nad+ metabolism leads to impaired cardiac mitochondrial function and communication. eLIFE. ISSN 2050-084X. 10, s. 1–23. doi: 10.7554/ELIFE.59828. Fulltekst i vitenarkiv
• Lambertus, Marvin; Øverberg, Linda Thøring; Andersson, Krister Andreas; Hjelden, Malin Sørli; Hadzic, Alena & Haugen, Øyvind Pernell [Vis alle 10 forfattere av denne artikkelen] (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
• Utheim, Tor Paaske; Chen, Xiangjun; Fricke, Otto; Bergersen, Linda Hildegard & Lagali, Neil Satish (2020). Microdot Accumulation in the Anterior Cornea with Aging–Quantitative Analysis with in Vivo Confocal Microscopy. Current Eye Research. ISSN 0271-3683. 45(9), s. 1058–1064. doi: 10.1080/02713683.2020.1725062.
• Cunnane, Stephen C.; Trushina, Eugenia; Morland, Cecilie; Prigione, Alessandro; Casadesus, Gemma & Andrews, Zane B [Vis alle 27 forfattere av denne artikkelen] (2020). Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nature Reviews Drug Discovery. ISSN 1474-1776. 19, s. 609–633. doi: 10.1038/s41573-020-0072-x. Fulltekst i vitenarkiv
• Hadzic, Alena; Nguyen, Teresa Dang; Hosoyamada, Makoto; Tomioka, Naoko H.; Bergersen, Linda Hildegard & Storm-Mathisen, Jon [Vis alle 7 forfattere av denne artikkelen] (2020). The Lactate Receptor HCA1 Is Present in the Choroid Plexus, the Tela Choroidea, and the Neuroepithelial Lining of the Dorsal Part of the Third Ventricle. International Journal of Molecular Sciences. ISSN 1661-6596. 21(18). doi: 10.3390/ijms21186457. Fulltekst i vitenarkiv
• Aman, Yahyah; Frank, Johannes; Lautrup, Sofie Hindkjær; Matysek, Adrian; Niu, Zhangming & Yang, Guang [Vis alle 13 forfattere av denne artikkelen] (2020). The NAD+-mitophagy axis in healthy longevity and in artificial intelligence-based clinical applications. Mechanisms of Ageing and Development. ISSN 0047-6374. 185, s. 1–11. doi: 10.1016/j.mad.2019.111194. Fulltekst i vitenarkiv
• Gilmour, Brian Christopher; Gudmundsrud, Ruben; Frank, Johannes; Hov, Amund; Hindkjær Lautrup, Sofie & Aman, Yahyah [Vis alle 18 forfattere av denne artikkelen] (2020). Targeting NAD+ in translational research to relieve diseases and conditions of metabolic stress and ageing. Mechanisms of Ageing and Development. ISSN 0047-6374. 186, s. 1–6. doi: 10.1016/j.mad.2020.111208. Fulltekst i vitenarkiv
• Haugen, Øyvind Pernell; Vallenari, Evan Michael; Belhaj, Imen; Småstuen, Milada Cvancarova; Storm-Mathisen, Jon & Bergersen, Linda Hildegard [Vis alle 7 forfattere av denne artikkelen] (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
• Fang, Fei; Nilsen, Hilde; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2019). NO-age in Norway. Translational Medicine of Aging. ISSN 2468-5011. 3, s. 37–39. doi: 10.1016/j.tma.2019.04.001.
• Vohra, Rupali; Aldana, Blanca I; Bulli, Giorgia; Skytt, Dorte M.; Waagepetersen, Helle & Bergersen, Linda Hildegard [Vis alle 7 forfattere av denne artikkelen] (2019). Lactate-Mediated Protection of Retinal Ganglion Cells. Journal of Molecular Biology (JMB). ISSN 0022-2836. 431(9), s. 1878–1888. doi: 10.1016/j.jmb.2019.03.005.
• Bækkerud, Fredrik Hjulstad; Salerno, Simona; Ceriotti, Paola; Morland, Cecilie; Storm-Mathisen, Jon & Bergersen, Linda Hildegard [Vis alle 9 forfattere av denne artikkelen] (2019). High intensity interval training ameliorates mitochondrial dysfunction in the left ventricle of mice with type 2 diabetes. Cardiovascular Toxicology. ISSN 1530-7905. 19(5), s. 422–431. doi: 10.1007/s12012-019-09514-z. Fulltekst i vitenarkiv Vis sammendrag

  UNIKARD (Project Number 217777/H10)

• Vohra, Rupali; Aldana, Blanca I; Waagepetersen, Helle; Bergersen, Linda Hildegard & Kolko, Miriam (2019). Dual Properties of Lactate in Müller Cells: The Effect of GPR81 Activation. Investigative Ophthalmology and Visual Science. ISSN 0146-0404. 60(4), s. 999–1008. doi: 10.1167/iovs.18-25458. Fulltekst i vitenarkiv
• Vohra, Rupali; Dalgaard, Line Marie; Vibæk, Jeppe; Langbøl, Mia Aggergaard; Bergersen, Linda Hildegard & Olsen, Niels Vidiendal [Vis alle 8 forfattere av denne artikkelen] (2019). Potential metabolic markers in glaucoma and their regulation in response to hypoxia. Acta Ophthalmologica. ISSN 1755-375X. s. 1–10. doi: 10.1111/aos.14021.
• Tari, Atefe R; Norevik, Cecilie Skarstad; Scrimgeour, Nathan Robert; Kobro-Flatmoen, Asgeir; Storm-Mathisen, Jon & Bergersen, Linda Hildegard [Vis alle 11 forfattere av denne artikkelen] (2019). Are the Neuroprotective Effects of Exercise Training Systemically Mediated? Progress in cardiovascular diseases. ISSN 0033-0620. 62(2), s. 94–101. doi: 10.1016/j.pcad.2019.02.003. Fulltekst i vitenarkiv
• Medin, Tirill; Jensen, Vidar; Skare, Øivind; Storm-Mathisen, Jon; Hvalby, Øyvind Christian & Bergersen, Linda Hildegard (2019). Altered α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function and expression in hippocampus in a rat model of attention-deficit/hyperactivity disorder (ADHD). Behavioural Brain Research. ISSN 0166-4328. 360, s. 209–215. doi: 10.1016/j.bbr.2018.12.028. Fulltekst i vitenarkiv Vis sammendrag

  Glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) carry the bulk of excitatory synaptic transmission. Their modulation plays key roles in synaptic plasticity, which underlies hippocampal learning and memory. A dysfunctional glutamatergic system may negatively affect learning abilities and underlie symptoms of attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to investigate whether the expression and function of AMPARs were altered in ADHD. We recorded AMPAR mediated synaptic transmission at hippocampal excitatory synapses and quantified immunogold labelling density of AMPAR subunits GluA1 and GluA2/3 in a rat model for ADHD; the spontaneously hypertensive rat (SHR). Electrophysiological recordings showed significantly reduced AMPAR mediated synaptic transmission at the CA3-to-CA1 pyramidal cell synapses in stratum radiatum and stratum oriens in SHRs compared to control rats. Electronmicroscopic immunogold quantifications did not show any statistically significant changes in labelling densities of the GluA1 subunit of the AMPAR on dendritic spines in stratum radiatum or in stratum oriens. However, there was a significant increase of the GluA2/3 subunit intracellularly in stratum oriens in SHR compared to control, interpreted as a compensatory effect. The proportion of synapses lacking AMPAR subunit labelling was the same in the two genotypes. In addition, electronmicroscopic examination of tissue morphology showed the density of this type of synapse (i.e., asymmetric synapses on spines), and the average size of the synaptic membranes, to be the same. AMPAR dysfunction, possibly involving molecular changes, in hippocampus may in part reflect altered learning in individuals with ADHD.

• Vohra, Rupali; Aldana, Blanca I; Skytt, Dorte M.; Freude, Kristine; Waagepetersen, Helle S. & Bergersen, Linda Hildegard [Vis alle 7 forfattere av denne artikkelen] (2018). Essential Roles of Lactate in Muller Cell Survival and Function. Molecular Neurobiology. ISSN 0893-7648. 55(12), s. 9108–9121. doi: 10.1007/s12035-018-1056-2.
• Medin, Tirill; Medin, Hege; Hefte, Marita Brandsar; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2018). Upregulation of the lactate transporter monocarboxylate transporter 1 at the blood-brain barrier in a rat model of attention-deficit/hyperactivity disorder suggests hyperactivity could be a form of self-treatment . Behavioural Brain Research. ISSN 0166-4328. 360, s. 279–285. doi: 10.1016/j.bbr.2018.12.023. Vis sammendrag

  The energy deficit hypothesis of attention-deficit/hyperactivity disorder (ADHD) suggests that low lactate production by brain astrocytes causes the symptoms of the disorder. Astrocytes are the main producers of lactate in the brain; however, skeletal muscles can produce the most lactate in the body. The lactate production by skeletal muscles increases with physical activity, as does the expression of the lactate transporter monocarboxylate transporter 1 (MCT1) at the blood-brain barrier (BBB). We hypothesise that children with ADHD, by being hyperactive, increase lactate production by skeletal muscles and transport it into the brain to compensate for low supply by astrocytes. The aim of this study was to explore whether the level of MCT1 is altered in the brain in an animal model of ADHD. The MCT1 expression was quantified on hippocampal brain sections from the best available rat model of ADHD, i.e., the spontaneously hypertensive rat (SHR) (n=12), and the relevant control, the Wistar Kyoto rat (WKY) (n=12), by the use of quantitative immunofluorescence laser scanning microscopy and postembedding immunogold electron microscopy. The results revealed significantly higher levels of hippocampal MCT1 immunoreactivity in SHR compared to WKY, particularly at the BBB. These results indicate that lactate flux through MCT1 between the body and the brain could be upregulated in children with ADHD. This study adds to previous research suggesting hyperactivity may be beneficial in ADHD; Children with ADHD possibly display a hyperactive behaviour in order to raise skeletal muscle lactate production, MCT1 expression and flux over the BBB to supply the brain with lactate.

• Hasan-Olive, Md Mahdi; Lauritzen, Knut Husø; Ali, Mohammad Abdulla; Rasmussen, Lene Juel; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2018). A ketogenic diet improves mitochondrial biogenesis and bioenergetics via the PGC1α-SIRT3-UCP2 axis. Neurochemical Research. ISSN 0364-3190. s. 1–16. doi: 10.1007/s11064-018-2588-6.
• Thomsen, Kirsten; Yokota, Takashi; Hasan-Olive, Md Mahdi; Sherazi, Niloofar; Fakouri, Nima Borhan & Desler, Claus [Vis alle 12 forfattere av denne artikkelen] (2018). Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus. Neurobiology of Aging. ISSN 0197-4580. 61, s. 215–224. doi: 10.1016/j.neurobiolaging.2017.08.004.
• Vardjan, Nina; Chowdhury, Helena H.; Horvat, Anemari; Velebit, Jelena; Malnar, Maja & Muhic, Marko [Vis alle 16 forfattere av denne artikkelen] (2018). Enhancement of astroglial aerobic glycolysis by extracellular lactate-mediated increase in cAMP. Frontiers in Molecular Neuroscience. ISSN 1662-5099. 11. doi: 10.3389/fnmol.2018.00148. Fulltekst i vitenarkiv
• Fakouri, Nima Borhan; Durhuus, Jon Ambæk; Regnell, Christine E; Angleys, Maria; Desler, Claus & Hasan-Olive, Md Mahdi [Vis alle 14 forfattere av denne artikkelen] (2017). Rev1 contributes to proper mitochondrial function via the PARP-NAD+-SIRT1-PGC1α axis. Scientific Reports. ISSN 2045-2322. 7(1). doi: 10.1038/s41598-017-12662-3.
• Vohra, Rupali; Gurubaran, I. S.; Henriksen, Ulrik; Bergersen, Linda Hildegard; Rasmussen, Lene Juel & Desler, Claus [Vis alle 8 forfattere av denne artikkelen] (2017). Disturbed mitochondrial function restricts glutamate uptake in the human Muller glia cell line, MIO-M1. Mitochondrion (Amsterdam. Print). ISSN 1567-7249. 36, s. 52–59. doi: 10.1016/j.mito.2017.02.003.
• Jackson, Catherine; Reppe, Sjur; Eidet, Jon Roger; Eide, Lars; Tønseth, Kim Alexander & Bergersen, Linda Hildegard [Vis alle 9 forfattere av denne artikkelen] (2017). Optimization of storage temperature for Retention of Undifferentiated cell character of cultured human epidermal cell sheets. Scientific Reports. ISSN 2045-2322. 7:8206, s. 1–14. doi: 10.1038/s41598-017-08586-7.
• Morland, Cecilie; Andersson, Krister; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv & Gille, Andreas [Vis alle 21 forfattere av denne artikkelen] (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.

• Saeed, Muhammad; Rafiq, Sikander; Bergersen, Linda Hildegard & Deng, Liyuan (2017). Tailoring of water swollen PVA membrane for hosting carriers in CO2 facilitated transport membranes. Separation and Purification Technology. ISSN 1383-5866. 179, s. 550–560. doi: 10.1016/j.seppur.2017.02.022.
• Hamilton, Nicola; Clarke, Laura E.; Arancibia-Carcamo, I. Lorena; Kougioumtzidou, Eleni; Matthey, Moritz & Karadottir, Ragnhildur [Vis alle 10 forfattere av denne artikkelen] (2017). Endogenous GABA controls oligodendrocyte lineage cell number, myelination, and CNS internodelength. Glia. ISSN 0894-1491. 65(2), s. 309–321. doi: 10.1002/glia.23093. Fulltekst i vitenarkiv
• Skytt, D. M.; Toft-Kehler, A. K.; Brændstrup, C. T.; Cejvanovic, S.; Gurubaran, I. S. & Bergersen, Linda Hildegard [Vis alle 7 forfattere av denne artikkelen] (2016). Glia-neuron interactions in the retina can be studied in cocultures of Müller cells and retinal ganglion cells. BioMed Research International. ISSN 2314-6133. 2016. doi: 10.1155/2016/1087647. Fulltekst i vitenarkiv
• Lauritzen, Knut Husø; Hasan-Olive, Md Mahdi; Regnell, Christine E; Kleppa, Liv; Scheibye Knudsen, Morten & Gjedde, Albert [Vis alle 10 forfattere av denne artikkelen] (2016). A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain. Neurobiology of Aging. ISSN 0197-4580. 48, s. 34–47. doi: 10.1016/j.neurobiolaging.2016.08.005.
• Holm-Hansen, Signe; Low, J.K.; Zieba, J; Gjedde, A.; Bergersen, Linda Hildegard & Karl, Tim (2016). Behavioural effects of high fat diet in a mutant mouse model for the schizophrenia risk gene neuregulin 1. Genes, Brain and Behavior. ISSN 1601-1848. 15(3), s. 295–304. doi: 10.1111/gbb.12267. Vis sammendrag

  Schizophrenia patients are often obese or overweight and poor dietary choices appear to be a factor in this phenomenon. Poor diet has been found to have complex consequences for the mental state of patients. Thus, this study investigated whether an unhealthy diet (i.e. high fat diet: HFD) impacts on the behaviour of a genetic mouse model for the schizophrenia risk gene neuregulin 1 (i.e. transmembrane domain Nrg1 mutant mice: Nrg1 HET). Female Nrg1 HET and wild type-like littermates (WT) were fed with either HFD or a control chow diet. The mice were tested for baseline (e.g. anxiety) and schizophrenia-relevant behaviours after 7 weeks of diet exposure. HFD increased body weight and impaired glucose tolerance in all mice. Only Nrg1 females on HFD displayed a hyper-locomotive phenotype as locomotion-suppressive effects of HFD were only evident in WT mice. HFD also induced an anxiety-like response and increased freezing in the context and the cued version of the fear conditioning task. Importantly, CHOW-fed Nrg1 females displayed impaired social recognition memory, which was absent in HFD-fed mutants. Sensorimotor gating deficits of Nrg1 females were not affected by diet. In summary, HFD had complex effects on the behavioural phenotype of test mice and attenuated particular cognitive deficits of Nrg1 mutant females. This topic requires further investigations thereby also considering other dietary factors of relevance for schizophrenia as well as interactive effects of diet with medication and sex.

• Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L.; Hasan, Mahdi; Diget, Elisabeth Holm & Vohra, Rupali [Vis alle 13 forfattere av denne artikkelen] (2016). Lactate transport and receptor actions in retina: potential roles in retinal function and disease. Neurochemical Research. ISSN 0364-3190. 41(6), s. 1229–1236. doi: 10.1007/s11064-015-1792-x.
• Rinholm, Johanne Egge; Vervaeke, Koen Gerard Alois; Tadross, Michael; Tkachuk, Ariana; Kopek, Benjamin & Brown, Timothy A [Vis alle 8 forfattere av denne artikkelen] (2016). Movement and structure of mitochondria in oligodendrocytes and their myelin sheaths. Glia. ISSN 0894-1491. 64(5), s. 810–825. doi: 10.1002/glia.22965. Vis sammendrag

  Mitochondria play several crucial roles in the life of oligodendrocytes. During development of the myelin sheath they are essential providers of carbon skeletons and energy for lipid synthesis. During normal brain function their consumption of pyruvate will be a key determinant of how much lactate is available for oligodendrocytes to export to power axonal function. Finally, during calcium-overload induced pathology, as occurs in ischemia, mitochondria may buffer calcium or induce apoptosis. Despite their important functions, very little is known of the properties of oligodendrocyte mitochondria, and mitochondria have never been observed in the myelin sheaths. We have now used targeted expression of fluorescent mitochondrial markers to characterize the location and movement of mitochondria within oligodendrocytes. We show for the first time that mitochondria are able to enter and move within the myelin sheath. Within the myelin sheath the highest number of mitochondria was in the cytoplasmic ridges along the sheath. Mitochondria moved more slowly than in neurons and, in contrast to their behavior in neurons and astrocytes, their movement was increased rather than inhibited by glutamate activating NMDA receptors. By electron microscopy we show that myelin sheath mitochondria have a low surface area of cristae, which suggests a low ATP production. These data specify fundamental properties of the oxidative phosphorylation system in oligodendrocytes, the glial cells that enhance cognition by speeding action potential propagation and provide metabolic support to axons.

• Lauritzen, Knut Husø; Kleppa, Liv; Aronsen, Jan Magnus; Eide, Lars; Carlsen, Harald & Haugen, Øyvind Pernell [Vis alle 12 forfattere av denne artikkelen] (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.
• Gundersen, Vidar; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2015). Neuroglial transmission. Physiological Reviews. ISSN 0031-9333. 95(3), s. 695–726. doi: 10.1152/physrev.00024.2014.
• Morland, Cecilie; Lauritzen, Knut Husø; Puchades, Maja Amedjkouh; Holm-Hansen, Signe; Andersson, Krister & Gjedde, Albert [Vis alle 9 forfattere av denne artikkelen] (2015). The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1: Expression and action in brain. Journal of Neuroscience Research. ISSN 0360-4012. 93(7), s. 1045–1055. doi: 10.1002/jnr.23593.
• Bergersen, Linda Hildegard (2015). Lactate transport and signaling in the brain: potential therapeutic targets and roles in body-brain interaction . Journal of Cerebral Blood Flow and Metabolism. ISSN 0271-678X. 35(2), s. 176–185. doi: 10.1038/jcbfm.2014.206.
• Lauritzen, Fredrik; Eid, Tore & Bergersen, Linda Hildegard (2015). Monocarboxylate transporters in temporal lobe epilepsy: roles of lactate and ketogenic diet. Brain Structure and Function. ISSN 1863-2653. 220(1), s. 1–12. doi: 10.1007/s00429-013-0672-x. Vis sammendrag

  Epilepsy is a serious neurological disorder that affects approximately 1 % of the general population, making it one of the most common disorders of the central nervous system. Furthermore, up to 40 % of all patients with epilepsy cannot control their seizures with current medications. More efficacious treatments for medication refractory epilepsy are therefore needed. A better understanding of the mechanisms that cause this disorder is likely to facilitate the discovery of such treatments. Impairment in cerebral energy metabolism has been proposed as a possible causative factor in the pathogenesis of temporal lobe epilepsy (TLE), which is one of the most common types of medication-refractory epilepsies in adults. In this review, we will discuss some of the current hypotheses regarding the possible causal relationship between brain energy metabolism and TLE. Emphasis will be placed on the role of energy substrates (lactate and ketone bodies) and their transporter molecules, particularly monocarboxylate transporters 1 and 2 (MCT1 and MCT2). We recently reported that the cellular distribution of MCT1 and MCT2 is perturbed in the hippocampus in patients with TLE. The changes may be an adaptive response aimed at keeping high levels of lactate in the epileptic tissue, which may serve to counteract epileptic activity by downregulating cAMP levels through the lactate receptor GPR81, newly discovered in hippocampus. We propose that the perturbation of MCTs may be further involved in the pathophysiology of TLE by influencing brain energy homeostasis, mitochondrial function, GABA-ergic and glutamatergic neurotransmission, and flux of lactate through the brain.

• Lauritzen, Knut Husø; Morland, Cecilie; Puchades, Maja Amedjkouh; Holm-Hansen, Signe; Hagelin, Else Marie Valbjørn & Lauritzen, Fredrik [Vis alle 10 forfattere av denne artikkelen] (2014). Lactate receptor sites link neurotransmission, neurovascular coupling, and brain energy metabolism. Cereb Cortex. Cerebral Cortex. ISSN 1047-3211. s. 2784–2795. doi: 10.1093/cercor/bht136.
• Knudsen Scheibye, Morten; Mitchell, SJ; Fang, EF; Iyama, T; Ward, T. & Wang, J [Vis alle 22 forfattere av denne artikkelen] (2014). A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in cockayne syndrome . Cell Metabolism. ISSN 1550-4131. 20(5), s. 840–855. doi: 10.1016/j.cmet.2014.10.005.
• Edin, Nina Frederike J; Sandvik, Joe Alexander; Chang, Cheng; Bergersen, Linda Hildegard & Pettersen, Erik O (2014). The roles of TGF-β3 and peroxynitrite in removal of hyper-radiosensitivity by priming irradiation. International Journal of Radiation Biology. ISSN 0955-3002. 90(7), s. 527–537. doi: 10.3109/09553002.2014.906767.
• Mariga, Shelton T.; Kolko, Miriam; Gjedde, Albert & Bergersen, Linda Hildegard (2014). Lactate transport and receptor actions in cerebral malaria. Frontiers in Neuroenergetics. ISSN 1662-6427. 6(MAY). doi: 10.3389/fnins.2014.00125. Fulltekst i vitenarkiv
• Rinholm, Johanne Egge & Bergersen, Linda Hildegard (2014). White matter lactate - Does it matter? Neuroscience. ISSN 0306-4522. 276, s. 109–116. doi: 10.1016/j.neuroscience.2013.10.002.
• Rasmussen, Lene Juel; Shiloh, Y.; Bergersen, Linda Hildegard; Sander, Miriam; Bohr, Vilhelm A. & Tønjum, Tone (2013). DNA damage response, bioenergetics, and neurological disease: The challenge of maintaining brain health in an aging human population. Mechanisms of Ageing and Development. ISSN 0047-6374. 134(10), s. 427–433. doi: 10.1016/j.mad.2013.05.001.
• Rodell, Anders; Rasmussen, Lene Juel; Bergersen, Linda Hildegard; Singh, KK & Gjedde, Albert (2013). Natural selection of mitochondria during somatic lifetime promotes healthy aging. Frontiers in Neuroenergetics. ISSN 1662-6427. doi: 10.3389/fnene.2013.00007. Vis sammendrag

  Stimulation of mitochondrial biogenesis during life-time challenges both eliminates disadvantageous properties and drives adaptive selection of advantageous phenotypic variations. Intermittent fission and fusion of mitochondria provide specific targets for health promotion by brief temporal stressors, interspersed with periods of recovery and biogenesis. For mitochondria, the mechanisms of selection, variability, and heritability, are complicated by interaction of two independent genomes, including the multiple copies of DNA in each mitochondrion, as well as the shared nuclear genome of each cell. The mechanisms of stress-induced fission, followed by recovery-induced fusion and biogenesis, drive the improvement of mitochondrial functions, not only as directed by genotypic variations, but also as enabled by phenotypic diversity. Selective adaptation may explain unresolved aspects of aging, including the health effects of exercise, hypoxic and poisonous preconditioning, and tissue-specific mitochondrial differences. We propose that intermittent purposeful enhancement of mitochondrial biogenesis by stressful episodes with subsequent recovery paradoxically promotes adaptive mitochondrial health and continued healthy aging.

• Lauritzen, Knut Husø; Morland, Cecilie; Puchades, Maja Amedjkouh; Holm-Hansen, Signe; Hagelin, Else Marie Valbjørn & Lauritzen, Fredrik [Vis alle 10 forfattere av denne artikkelen] (2013). Lactate Receptor Sites Link Neurotransmission, Neurovascular Coupling, and Brain Energy Metabolism. Cerebral Cortex. ISSN 1047-3211. doi: 10.1093/cercor/bht136. Vis sammendrag

  The G-protein-coupled lactate receptor, GPR81 (HCA1), is known to promote lipid storage in adipocytes by downregulating cAMP levels. Here, we show that GPR81 is also present in the mammalian brain, including regions of the cerebral neocortex and hippocampus, where it can be activated by physiological concentrations of lactate and by the specific GPR81 agonist 3,5-dihydroxybenzoate to reduce cAMP. Cerebral GPR81 is concentrated on the synaptic membranes of excitatory synapses, with a postsynaptic predominance. GPR81 is also enriched at the blood-brain-barrier: the GPR81 densities at endothelial cell membranes are about twice the GPR81 density at membranes of perivascular astrocytic processes, but about one-seventh of that on synaptic membranes. There is only a slight signal in perisynaptic processes of astrocytes. In synaptic spines, as well as in adipocytes, GPR81 immunoreactivity is located on subplasmalemmal vesicular organelles, suggesting trafficking of the protein to and from the plasma membrane. The results indicate roles of lactate in brain signaling, including a neuronal glucose and glycogen saving response to the supply of lactate. We propose that lactate, through activation of GPR81 receptors, can act as a volume transmitter that links neuronal activity, cerebral energy metabolism and energy substrate availability.

• Nagelhus, Erlend Arnulf; Amiry-Moghaddam, Mahmood ; Bergersen, Linda Hildegard; Bjaalie, Jan G.; Eriksson, Jens & Gundersen, Vidar [Vis alle 12 forfattere av denne artikkelen] (2013). The glia doctrine: Addressing the role of glial cells in healthy brain ageing. Mechanisms of Ageing and Development. ISSN 0047-6374. 134(10), s. 449–459. doi: 10.1016/j.mad.2013.10.001.
• Puchades, Maja Amedjkouh; Sogn, Carl Johan; Mæhlen, Jan; Bergersen, Linda Hildegard & Gundersen, Vidar (2013). Unaltered lactate and glucose transporter levels in the MPTP mouse model of Parkinson's disease. Parkinson's Disease. ISSN 2090-8083. 3(3), s. 371–385. doi: 10.3233/JPD-130190.
• Medin, Tirill; Rinholm, Johanne Egge; Owe, Simen Gylterud; Sagvolden, Terje; Gjedde, A. & Storm-Mathisen, Jon [Vis alle 7 forfattere av denne artikkelen] (2013). LOW DOPAMINE D5 RECEPTOR DENSITY IN HIPPOCAMPUS IN AN ANIMAL MODEL OF ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD). Neuroscience. ISSN 0306-4522. 242, s. 11–20. doi: 10.1016/j.neuroscience.2013.03.036.

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• Fang, Fei; Bergersen, Linda Hildegard & Gilmour, Brian Christopher (2023). Molecular, Cellular, and Metabolic Fundamentals of Human Aging. Academic Press. ISBN 978-0-323-91617-2. 246 s.
• Åmellem, Ingrid; Bergersen, Linda Hildegard & Storm-Mathisen, Jon (2019). VNPN-2 Conference Booklet Virginia-Nordic Precision Neuroscience II: From Discovery to Translation and Innovation – Oslo, Norway, 19-21 September 2018. Virginia-Nordic Precision Neuroscience (http://www.vnpn.science/). ISBN 978-82-995010-4-0. 30 s.
• Bergersen, Linda Hildegard (2013). Brain Energy 2013 – Current Advances in Brain Maintenance. DNVA: www.dnva.no/binfil/download.php?tid=58301. ISBN 82-995010-2-4. 18 s.

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• Bergersen, Linda Hildegard; Petersen, Fernanda Cristina & Dahle, Ulf R (2020). Kort sagt, fredag 27. mars. [Avis]. Aftenposten.
• Bergersen, Linda Hildegard; Bjorvand Bjørkøy, Aasta Marie; Fei Fang, Evandro; Gjelsvik, Olav; Hystad Hove, Lene & Liaaen Jensen, Janicke [Vis alle 12 forfattere av denne artikkelen] (2020). Vi må kunne tenke nytt om alderdom.
• Fakouri, Nima Borhan; Durhuus, Jon Ambæk; Regnell, Christine E; Angleys, Maria; Desler, Claus & Hasan-Olive, Md Mahdi [Vis alle 14 forfattere av denne artikkelen] (2018). Erratum: Author Correction: Rev1 contributes to proper mitochondrial function via the PARP-NAD⁺-SIRT1-PGC1α axis (Scientific reports (2017) 7 1 (12480)). Scientific Reports. ISSN 2045-2322. 8(1). doi: 10.1038/s41598-018-20586-9.
• Øverberg, Linda Thøring; Andersson, Krister Andreas; Lambertus, Marvin; Hadzic, Alena; Haugen, Øyvind Pernell & Storm-Mathisen, Jon [Vis alle 8 forfattere av denne artikkelen] (2018). Adult neurogenesis: A regulatory role of lactate through the lactate receptor HCAR1? .
• Andersson, Krister; Morland, Cecilie; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv & Gille, Andreas [Vis alle 21 forfattere av denne artikkelen] (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.

• 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.

• Jensen, Jørgen; Storm-Mathisen, Jon; Bergersen, Linda Hildegard; Wærhaug, Ola; Samuelsen, Gunnar & Osen, Kirsten Kjelsberg (2017). Minneord: Hans A. Dahl. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 137, s. 14–15. doi: 10.4045/tidsskr.17.0487.
• Bergersen, Linda Hildegard (2016). Novel mechanism for exercise‐induced angiogenesis in the brain.
• Bergersen, Linda Hildegard (2016). The lactate receptor is important for brain vascularization.
• Morland, Cecilie; Andersson, Krister; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv & Gille, Andreas [Vis alle 18 forfattere av denne artikkelen] (2016). A novel mechanism for cerebral angiogenesis via lactate receptor HCAR1 at pial vessels.
• Hadzic, Alena; Andersson, Krister; Haugen, Øyvind Pernell; Storm-Mathisen, Jon; Stølen, Tomas & Wisløff, Ulrik [Vis alle 8 forfattere av denne artikkelen] (2016). Lactate receptor HCAR1 mediates synaptic plasticity.
• Moretti, Laura; Stølen, Tomas; Wisløff, Ulrik; Storm-Mathisen, Jon; Bergersen, Linda Hildegard & Morland, Cecilie (2016). Effects of intrinsic fitness level on mitochondria during exercise .
• Morland, Cecilie; Andersson, Krister; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv & Gille, Andreas [Vis alle 18 forfattere av denne artikkelen] (2016). Exercise induces cerebral angiogenesis via lactate receptor HCAR1 at pial vessels.
• Bergersen, Linda Hildegard (2016). Exercise induces brain VEGFA and angiogenesis through the lactate receptor.
• Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L.; Hasan-Olive, Md Mahdi; Diget, Elisabeth Holm & Vohra, Rupali [Vis alle 13 forfattere av denne artikkelen] (2016). Erratum to: Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease. Neurochemical Research. ISSN 0364-3190. 41(6), s. 1237–1237. doi: 10.1007/s11064-016-1916-y.
• Bergersen, Linda Hildegard (2016). Hvor ligger forskningsfronten innen demens nå? Hva vet vi og hva vet vi ikke?
• Bergersen, Linda Hildegard (2016). "Lactate transport and receptor action in the brain: rescue of cognitive decline” .
• Bergersen, Linda Hildegard (2016). The brain has a lactate receptor.
• Larsson, Max; Bergersen, Linda Hildegard & Gundersen, Vidar (2015). Immunogold electron microscopic quantification of small molecular compounds and proteins at synapses and other neural profiles. I Merighi, Adalberto & Lossi, Laura (Red.), Immunocytochemistry and related techniques. Springer. ISSN 978-1-4939-2312-0. s. 281–297. doi: 10.1007/978-1-4939-2313-7_15.
• Jackson, Catherine; Eidet, Jon Roger; Reppe, Sjur; Eide, Lars; Tønseth, Kim Aleksander & Bergersen, Linda Hildegard [Vis alle 9 forfattere av denne artikkelen] (2015). Storage of cultured skin cell sheets for treatment of limbal stem cell deficiency.
• Bergersen, Linda Hildegard (2015). Lactate Transport and Signaling in the Brain: Potential Therapeutic Targets and Roles in Body-Brain Interaction.
• Bergersen, Linda Hildegard (2015). Gir melkesyre bedre hjernehelse?
• Bergersen, Linda Hildegard (2015). Clinical use of lactate monitoring in malaria.
• Bergersen, Linda Hildegard (2015). Lactate transport and signaling in the brain: potential therapeutic targets and roles in body-brain interaction.
• Bergersen, Linda Hildegard (2015). Monocarboxylate transporters and lactate receptor expression and function in the brain.
• Bergersen, Linda Hildegard (2015). Lactate transport and receptor actions in cerebral malaria.
• Bergersen, Linda Hildegard (2015). Exercise in healthy aging.
• Bergersen, Linda Hildegard (2014). Professor i fysiologi, ekspert i sund aldring. [Internett]. iform.dk - advisory-board.
• Bergersen, Linda Hildegard (2014). Professor i fysiologi och expert på sunt åldrande. [Internett]. iform.se - expertpanelen.
• Bergersen, Linda Hildegard (2014). I FORM ekspert med spesiale: Sunn aldring. [Internett]. iFORM.nu.
• Bergersen, Linda Hildegard (2014). Mutasjon i transportørgen kan gi ketoacidose. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 134(23/24), s. 2257–2257. doi: 10.4045/tidsskr.14.1326.
• Bergersen, Linda Hildegard (2014). Trening for et bedre og lengre liv - Hjerne og trening.
• Bergersen, Linda Hildegard (2014). Trening for hjernehelse.
• Bergersen, Linda Hildegard (2014). The brain lactate receptor – does it matter in cognitive impairment.
• Bergersen, Linda Hildegard (2014). Lactate as messenger in the CNS.
• Bergersen, Linda Hildegard (2014). A ketogenic diet accelerates neurodegeneration in forebrain neurons during mitochondrial DNA toxicity.
• Bergersen, Linda Hildegard (2014). Lactate receptor in the brain.
• Bergersen, Linda Hildegard & Eid, Tore (2014). Monocarboxylate transport matters. New England Journal of Medicine. ISSN 0028-4793. 371(20), s. 1931–1932. doi: 10.1056/NEJMe1411903.
• Bergersen, Linda Hildegard (2013). Laktat har signalfunksjon i hjernen. [Fagblad]. Tidsskrift for Den norske legeforening.
• Bergersen, Linda Hildegard (2013). Lactate is a volume transmitter – 'New Deal' for understanding brain function and brain disease.
• Bergersen, Linda Hildegard (2013). Melkesyre har en egen reseptor i hjernen- viktig for den aldrende hjernen?
• Bergersen, Linda Hildegard (2013). Views from new research group Leader: how to succeed as leader and to build a new group?
• Bergersen, Linda Hildegard (2013). Lactate receptor in the Brain.
• Bergersen, Linda Hildegard (2013). How to implement brain research methods in exercise medicine? Lactate as a signal substance. How does physical exercise translate onto better brains?

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