Linda Hildegard Bergersen

• Belhaj, Imen; Åmellem, Ingrid; Tartanoglu, Can H.; Weidemann, Hanne Margrete; Vallenari, Evan Michael & Yang, Mingyi [Vis alle 10 forfattere av denne artikkelen] (2026). Lactate treatment improves brain biochemistry and cognitive function in transgenic Alzheimer’s and wild-type mice. Scientific Reports. 16(1). doi: 10.1038/s41598-026-48154-6. Fulltekst i vitenarkiv Vis sammendrag

  Lactate, a well-known metabolite and signalling molecule, holds therapeutic potential for neurodegenerative diseases. Here, we investigated the effects of chronic lactate treatment on cognition and molecular biomarkers in the 5XFAD mouse model of Alzheimer’s disease (AD) and in wild-type (WT) controls using behavioural testing alongside proteomic and transcriptomic analyses. Mice received lactate or vehicle injections 4 days per week for 11 weeks, with behavioural testing before and after the treatment period. Lactate improved working memory in late-treated AD mice, without eliciting anxiety-like behaviour. At the molecular level, lactate reduced Il1b expression, and in a sex-dependent manner, normalised NEFL, and enhanced synaptic integrity proteins (OPCML, PPFIA2, STXBP3, SYT1, VGLUT2, VSNL1) in AD mice, while also augmenting mitochondrial regulators (ATP5G2, GRPEL1, SLC25A23) across genotypes. Notably, lactate upregulated low-abundance ionotropic glutamate receptor mRNAs (Grik3, Grin2c, Grid2ip) in female AD mice, indicating enhanced glutamatergic signalling. In WT mice, lactate increased expression of neurotrophic factors (Bdnf, Igf1, Vegfa), anti-inflammatory cytokines (Il4 and Il13), and the neuronal lactate transporter Mct2, suggesting promoted neuronal resilience. Together, these findings indicate that lactate treatment can mitigate cognitive decline and enhance molecular pathways of resilience in AD, warranting larger, age-stratified studies to validate its therapeutic potential and elucidate underlying mechanisms.

• Ai, Ruixue; Mao, Lipeng; Jin, Xurui; Campos-Marques, Carlos; Zhang, Shi-qi & Pan, Junping [Vis alle 33 forfattere av denne artikkelen] (2025). NAD+ reverses Alzheimer’s neurological deficits via regulating differential alternative RNA splicing of EVA1C. Science Advances. 11(45). doi: 10.1126/sciadv.ady9811. Fulltekst i vitenarkiv Vis sammendrag

  Dysfunctional alternative splicing events (ASEs) in RNA are markers of aging and Alzheimer’s disease (AD). As a key neuronal resilience metabolite, the oxidized nicotinamide adenine dinucleotide (NAD+) slows down AD progression in preclinical studies with several clinical trials ongoing. However, the underlying molecular mechanisms around how NAD+ enhances neuronal resilience, especially whether it has any effect on ASEs, have remained elusive. This study shows that NAD+ augmentation corrects the ASEs of many genes via a key protein, EVA1C (epithelial V-like antigen 1 homolog C), which is involved in neuronal development and activities. EVA1C is reduced in the hippocampus in patients with AD compared to cognitively normal ones. NAD+-induced memory retention is partially dependent on EVA1C, as adeno-associated virus–based Eva1c knockdown in the hippocampal CA1 region annuls NAD+-induced memory improvement in pathological Tau–bearing mice. We propose that NAD+ reduces AD pathologies, at least partially, via amplification of the NAD+-EVA1C splicing axis, pointing to a potential splice-switching therapy for AD.

• Kennedy, Lauritz Hagen; Morland, Cecilie; Narum, Martine; Bergersen, Linda Hildegard & Rinholm, Johanne Egge (2025). Lactate Receptor HCAR1 Affects Axonal Development and Contributes to Lactate’s Protection of Axons and Myelin in Experimental Neonatal Hypoglycemia. eNeuro. 12(5). doi: 10.1523/eneuro.0563-24.2025. Fulltekst i vitenarkiv Vis sammendrag

  Lactate plays an important role in brain energy metabolism. It contributes to normal brain development and to neuroprotection in diabetic hypoglycemia, but its role in neonatal hypoglycemia is unclear. Moreover, lactate can work as a signaling substance via the lactate receptor HCAR1 (Hydroxycarboxylic acid receptor 1). Recent studies indicate that HCAR1 is protective in mouse models of neonatal hypoxic ischemia and has a role in metabolic regulation in glial cells during hypoglycemia. Here we have studied potential impacts of HCAR1 on axonal and myelin development in the cerebral cortex and corpus callosum of young (P21) wild-type (WT) mice and HCAR1 KO mice and in cortical organotypic brain slice cultures. The HCAR1 KO mice showed lower axonal area relative to WT in both cortex and corpus callosum. However, the myelin area was unaffected by HCAR1 KO. Using particle and colocalization analysis, we show that HCAR1 KO predominantly reduces axonal size in unmyelinated axons. Using an organotypic brain slice model of neonatal hypoglycemia, we find that lactate protects both axonal and myelin development in hypoglycemia, partially via HCAR1. Lastly, live imaging with a pH-sensitive dye on acute cortical brain slices indicates that cellular lactate uptake is influenced by HCAR1. In conclusion, our findings support a role of HCAR1 in axonal development and in lactate’s protective effects in hypoglycemia.

• Pietilä, Riikka; Gaudio, Francesca Del; 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 Vis sammendrag

  Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.

• Norevik, Cecilie Skarstad; Huuha, Aleksi Matias; Røsbjørgen, Ragnhild; Bergersen, Linda Hildegard; Jacobsen, Kamilla & Santos, Rodrigo Miguel dos [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 Vis sammendrag

  Background Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer's disease (AD). These beneficial effects may be partly mediated by blood-borne factors. Here we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability, and an in vivo rat model of AD to test whether such plasma impacts cognitive function, amyloid pathology, and neurogenesis. Methods Mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-β and treated with plasma collected from human male donors 3 h after a single bout of high-intensity exercise. For in vivo studies, blood was collected from exercise-trained young male Wistar rats (high-intensity intervals 5 days/week for 6 weeks). Transgenic AD rats (McGill-R-Thy1-APP) were injected 5 times/fortnight for 6 weeks at 2 months or 5 months of age with either (a) plasma from the exercise-trained rats, (b) plasma from sedentary rats, or (c) saline. Cognitive function, amyloid plaque pathology, and neurogenesis were assessed. The plasma used for the treatment was analyzed for 23 cytokines. Results Plasma from exercised donors enhanced cell viability by 44.1% (p = 0.032) and reduced atrophy by 50.0% (p < 0.001) in amyloid-β-treated cells. In vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by ∼3-fold, regardless of pathological stage, when compared to saline-treated rats. Concentrations of 7 cytokines were significantly reduced in exercised plasma compared to sedentary plasma. Conclusion Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat brain. This effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

• 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. 11. doi: 10.7554/eLife.76451. Fulltekst i vitenarkiv Vis sammendrag

  Neonatal cerebral hypoxia-ischemia (HI) is the leading cause of death and disability in newborns with the only current treatment being hypothermia. An increased understanding of the pathways that facilitate tissue repair after HI may aid the development of better treatments. Here, we study the role of lactate receptor HCAR1 in tissue repair after neonatal HI in mice. We show that HCAR1 knockout mice have reduced tissue regeneration compared with wildtype mice. Furthermore, proliferation of neural progenitor cells and glial cells, as well as microglial activation was impaired. Transcriptome analysis showed a strong transcriptional response to HI in the subventricular zone of wildtype mice involving about 7300 genes. In contrast, the HCAR1 knockout mice showed a modest response, involving about 750 genes. Notably, fundamental processes in tissue repair such as cell cycle and innate immunity were dysregulated in HCAR1 knockout. Our data suggest that HCAR1 is a key transcriptional regulator of pathways that promote tissue regeneration after HI.

• 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. 11(13). doi: 10.3390/cells11132098. Fulltekst i vitenarkiv Vis sammendrag

  Background: Progressive retinal ganglion cell (RGC) dysfunction and death are common characteristics of retinal neurodegenerative diseases. Recently, hydroxycarboxylic acid receptor 1 (HCA1R, GPR81) was identified as a key modulator of mitochondrial function and cell survival. Thus, we aimed to test whether activation of HCA1R with 3,5-Dihydroxybenzoic acid (DHBA) also promotes RGC survival and improves energy metabolism in mouse retinas. Methods: Retinal explants were treated with 5 mM of the HCA1R agonist, 3,5-DHBA, for 2, 4, 24, and 72 h. Additionally, explants were also treated with 15 mM of L-glutamate to induce toxicity. Tissue survival was assessed through lactate dehydrogenase (LDH) viability assays. RGC survival was measured through immunohistochemical (IHC) staining. Total ATP levels were quantified through bioluminescence assays. Energy metabolism was investigated through stable isotope labeling and gas chromatography-mass spectrometry (GC-MS). Lactate and nitric oxide levels were measured through colorimetric assays. Results: HCA1R activation with 3,5-DHBAincreased retinal explant survival. During glutamate-induced death, 3,5-DHBA treatment also increased survival. IHC analysis revealed that 3,5-DHBA treatment promoted RGC survival in retinal wholemounts. 3,5-DHBA treatment also enhanced ATP levels in retinal explants, whereas lactate levels decreased. No effects on glucose metabolism were observed, but small changes in lactate metabolism were found. Nitric oxide levels remained unaltered in response to 3,5-DHBA treatment. Conclusion: The present study reveals that activation of HCA1R with 3,5-DHBA treatment has a neuroprotective effect specifically on RGCs and on glutamate-induced retinal degeneration. Hence, HCA1R agonist administration may be a potential new strategy for rescuing RGCs, ultimately preventing visual disability.

• 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. 10, s. 1–23. doi: 10.7554/ELIFE.59828. Fulltekst i vitenarkiv Vis sammendrag

  Poly(ADP-ribose) polymerase (PARP) enzymes initiate (mt)DNA repair mechanisms and use nicotinamide adenine dinucleotide (NAD+) as energy source. Prolonged PARP activity can drain cellular NAD+ reserves, leading to de-regulation of important molecular processes. Here, we provide evidence of a pathophysiological mechanism that connects mtDNA damage to cardiac dysfunction via reduced NAD+ levels and loss of mitochondrial function and communication. Using a transgenic model, we demonstrate that high levels of mice cardiomyocyte mtDNA damage cause a reduction in NAD+ levels due to extreme DNA repair activity, causing impaired activation of NAD+-dependent SIRT3. In addition, we show that myocardial mtDNA damage in combination with high dosages of nicotinamideriboside (NR) causes an inhibition of sirtuin activity due to accumulation of nicotinamide (NAM), in addition to irregular cardiac mitochondrial morphology. Consequently, high doses of NR should be used with caution, especially when cardiomyopathic symptoms are caused by mitochondrial dysfunction and instability of mtDNA.

• 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. 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 Vis sammendrag

  Nicotinamide adenine dinucleotide (NAD+) is an important natural molecule involved in fundamental biological processes, including the TCA cycle, OXPHOS, β-oxidation, and is a co-factor for proteins promoting healthy longevity. NAD+ depletion is associated with the hallmarks of ageing and may contribute to a wide range of age-related diseases including metabolic disorders, cancer, and neurodegenerative diseases. One of the central pathways by which NAD+ promotes healthy ageing is through regulation of mitochondrial homeostasis via mitochondrial biogenesis and the clearance of damaged mitochondria via mitophagy. Here, we highlight the contribution of the NAD+-mitophagy axis to ageing and age-related diseases, and evaluate how boosting NAD+ levels may emerge as a promising therapeutic strategy to counter ageing as well as neurodegenerative diseases including Alzheimer’s disease. The potential use of artificial intelligence to understand the roles and molecular mechanisms of the NAD+-mitophagy axis in ageing is discussed, including possible applications in drug target identification and validation, compound screening and lead compound discovery, biomarker development, as well as efficacy and safety assessment. Advances in our understanding of the molecular and cellular roles of NAD+ in mitophagy will lead to novel approaches for facilitating healthy mitochondrial homoeostasis that may serve as a promising therapeutic strategy to counter ageing-associated pathologies and/or accelerated ageing.

• 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. 2020(1). doi: 10.7717/peerj.8328. Fulltekst i vitenarkiv Vis sammendrag

  Lactate treatment has shown a therapeutic potential for several neurological diseases, including Alzheimer’s disease. In order to optimize the administration of lactate for studies in mouse models, we compared blood lactate dynamics after intraperitoneal (IP) and subcutaneous (SC) injections. We used the 5xFAD mouse model for familial Alzheimer’s disease and performed the experiments in both awake and anaesthetized mice. Blood glucose was used as an indication of the hepatic conversion of lactate. In awake mice, both injection routes resulted in high blood lactate levels, mimicking levels reached during high-intensity training. In anaesthetized mice, SC injections resulted in significantly lower lactate levels compared to IP injections. Interestingly, we observed that awake males had significantly higher lactate levels than awake females, while the opposite sex difference was observed during anaesthesia. We did not find any significant difference between transgenic and wild-type mice and therefore believe that our results can be generalized to other mouse models. These results should be considered when planning experiments using lactate treatment in mice.

• 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 Vis sammendrag

  The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes.

• 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 Vis sammendrag

  The volume, composition, and movement of the cerebrospinal fluid (CSF) are important for brain physiology, pathology, and diagnostics. Nevertheless, few studies have focused on the main structure that produces CSF, the choroid plexus (CP). Due to the presence of monocarboxylate transporters (MCTs) in the CP, changes in blood and brain lactate levels are reflected in the CSF. A lactate receptor, the hydroxycarboxylic acid receptor 1 (HCA1), is present in the brain, but whether it is located in the CP or in other periventricular structures has not been studied. Here, we investigated the distribution of HCA1 in the cerebral ventricular system using monomeric red fluorescent protein (mRFP)-HCA1 reporter mice. The reporter signal was only detected in the dorsal part of the third ventricle, where strong mRFP-HCA1 labeling was present in cells of the CP, the tela choroidea, and the neuroepithelial ventricular lining. Co-labeling experiments identified these cells as fibroblasts (in the CP, the tela choroidea, and the ventricle lining) and ependymal cells (in the tela choroidea and the ventricle lining). Our data suggest that the HCA1-containing fibroblasts and ependymal cells have the ability to respond to alterations in CSF lactate in body–brain signaling, but also as a sign of neuropathology (e.g., stroke and Alzheimer’s disease biomarker).

• 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. 231(3). doi: 10.1111/apha.13587. Fulltekst i vitenarkiv Vis sammendrag

  Aim: Adult neurogenesis occurs in two major niches in the brain: the subgranular zone of the hippocampal formation and the ventricular-subventricular zone. Neurogenesis in both niches is reduced in ageing and neurological disease involving dementia. Exercise can rescue memory by enhancing hippocampal neurogenesis, but whether exercise affects adult neurogenesis in the ventricular-subventricular zone remains unresolved. Previously, we reported that exercise induces angiogenesis through ac- tivation of the lactate receptor HCA1. The aim of the present study is to investigate HCA1-dependent effects on neurogenesis in the two main neurogenic niches. Methods: Wild-type and HCA1 knock-out mice received high intensity interval ex- ercise, subcutaneous injections of L-lactate, or saline injections, five days per week for seven weeks. Well-established markers for proliferating cells (Ki-67) and imma- ture neurons (doublecortin), were used to investigate neurogenesis in the subgranular zone and the ventricular-subventricular zone. Results: We demonstrated that neurogenesis in the ventricular-subventricular zone is enhanced by HCA1 activation: Treatment with exercise or lactate resulted in in- creased neurogenesis in wild-type, but not in HCA1 knock-out mice. In the subgranu- lar zone, neurogenesis was induced by exercise in both genotypes, but unaffected by lactate treatment. Conclusion: Our study demonstrates that neurogenesis in the two main neurogenic niches in the brain is regulated differently: Neurogenesis in both niches was induced by exercise, but only in the ventricular-subventricular zone was neurogenesis in- duced by lactate through HCA1 activation. This opens for a role of HCA1 in the physiological control of neurogenesis, and potentially in counteracting age-related cognitive decline.

• Gilmour, Brian Christopher; Gudmundsrud, Ruben; Frank, Johannes; Hov, Amund; Lautrup, Sofie Hindkjær & 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 Vis sammendrag

  Nicotinamide adenine dinucleotide (NAD+) plays a fundamental role in life and health through the regulation of energy biogenesis, redox homeostasis, cell metabolism, and the arbitration of cell survival via linkages to apoptosis and autophagic pathways. The importance of NAD+ in ageing and healthy longevity has been revealed from laboratory animal studies and early-stage clinical testing. While basic researchers and clinicians have investigated the molecular mechanisms and translation potential of NAD+, there are still major gaps in applying laboratory science to design the most effective trials. This mini-review was based on the programme and discussions of the 3rd NO-Age Symposium held at the Akershus University Hospital, Norway on the 28th October 2019. This symposium brought together leading basic researchers on NAD+ and clinicians who are leading or are going to perform NAD+ augmentation-related clinical studies. This meeting covered talks about NAD+ synthetic pathways, subcellular homeostasis of NAD+, the benefits of NAD+ augmentation from maternal milk to offspring, current clinical trials of the NAD+ precursor nicotinamide riboside (NR) on Ataxia-Telangiectasia (A-T), Parkinson’s disease (PD), post-sepsis fatigue, as well as other potential NR-based clinical trials. Importantly, a consensus is emerging with respect to the design of clinical trials in order to measure meaningful parameters and ensure safety.

• 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 Vis sammendrag

  To date there is no cure available for dementia, and the field calls for novel therapeutic targets. A rapidly growing body of literature suggests that regular endurance training and high cardiorespiratory fitness attenuate cognitive impairment and reduce dementia risk. Such benefits have recently been linked to systemic neurotrophic factors induced by exercise. These circulating biomolecules may cross the blood-brain barrier and potentially protect against neurodegenerative disorders such as Alzheimer's disease. Identifying exercise-induced systemic neurotrophic factors with beneficial effects on the brain may lead to novel molecular targets for maintaining cognitive function and preventing neurodegeneration. Here we review the recent literature on potential systemic mediators of neuroprotection induced by exercise. We focus on the body of translational research in the field, integrating knowledge from the molecular level, animal models, clinical and epidemiological studies. Taken together, the current literature provides initial evidence that exercise-induced, blood-borne biomolecules, such as BDNF and FNDC5/irisin, may be powerful agents mediating the benefits of exercise on cognitive function and may form the basis for new therapeutic strategies to better prevent and treat dementia.

• 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 Vis sammendrag

  Purpose: Besides being actively metabolized, lactate may also function as a signaling molecule by activation of the G-protein–coupled receptor 81 (GPR81). Thus, we aimed to characterize the metabolic effects of GPR81 activation in Müller cells. Method: Primary Müller cells from mice were treated with and without 10 mM L-lactate in the presence or absence of 6 mM glucose. The effects of lactate receptor GPR81 activation were evaluated by the addition of 5 mM 3,5-DHBA (3,5-dihydroxybenzoic acid), a GPR81 agonist. Western blot analyses were used to determine protein expression of GPR81. Cell survival was assessed through 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assays. Lactate release was quantified by commercially available lactate kits. 13C-labeling studies via mass spectroscopy and Seahorse analyses were performed to evaluate metabolism of lactate and glucose, and mitochondrial function. Finally, Müller cell function was evaluated by measuring glutamate uptake. Results: The lactate receptor, GPR81, was upregulated during glucose deprivation. Treatment with a GPR81 agonist did not affect Müller cell survival. However, GPR81 activation diminished lactate release allowing lactate to be metabolized intracellularly. Furthermore, GPR81 activation increased metabolism of glucose and mitochondrial function. Finally, maximal glutamate uptake decreased in response to GPR81 activation during glucose deprivation. Conclusions: The present study revealed dual properties of lactate via functioning as an active metabolic energy substrate and a regulatory molecule by activation of the GPR81 receptor in primary Müller cells. Thus, combinational therapy of lactate and GPR81 agonists may be of future interest in maintaining Müller cell survival, ultimately leading to increased resistance toward retinal neurodegeneration.

• 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; 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. Fulltekst i vitenarkiv
• Vohra, Rupali; Dalgaard, Line Marie; Vibæk, Jeppe; Langbøl, Mia Aggergaard; Bergersen, Linda Hildegard & Olsen, Niels Vidiendal [Vis alle 9 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. Fulltekst i vitenarkiv
• Fang, Fei; Nilsen, Hilde; Storm-Mathisen, Jon & Bergersen, Linda Hildegard (2019). NO-age in Norway. Translational Medicine of Aging. 3, s. 37–39. doi: 10.1016/j.tma.2019.04.001. Fulltekst i vitenarkiv
• 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; 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• 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. 11. doi: 10.3389/fnmol.2018.00148. Fulltekst i vitenarkiv Vis sammendrag

  Besides being a neuronal fuel, L-lactate is also a signal in the brain. Whether extracellular L-lactate affects brain metabolism, in particular astrocytes, abundant neuroglial cells, which produce L-lactate in aerobic glycolysis, is unclear. Recent studies suggested that astrocytes express low levels of the L-lactate GPR81 receptor (EC50 ≈ 5 mM) that is in fat cells part of an autocrine loop, in which the Gi-protein mediates reduction of cytosolic cyclic adenosine monophosphate (cAMP). To study whether a similar signaling loop is present in astrocytes, affecting aerobic glycolysis, we measured the cytosolic levels of cAMP, D-glucose and L-lactate in single astrocytes using fluorescence resonance energy transfer (FRET)-based nanosensors. In contrast to the situation in fat cells, stimulation by extracellular L-lactate and the selective GPR81 agonists, 3-chloro-5-hydroxybenzoic acid (3Cl-5OH-BA) or 4-methyl-N-(5-(2-(4-methylpiperazin-1-yl)-2-oxoethyl)-4-(2-thienyl)-1,3-thiazol-2-yl)cyclohexanecarboxamide (Compound 2), like adrenergic stimulation, elevated intracellular cAMP and L-lactate in astrocytes, which was reduced by the inhibition of adenylate cyclase. Surprisingly, 3Cl-5OH-BA and Compound 2 increased cytosolic cAMP also in GPR81-knock out astrocytes, indicating that the effect is GPR81-independent and mediated by a novel, yet unidentified, excitatory L-lactate receptor-like mechanism in astrocytes that enhances aerobic glycolysis and L-lactate production via a positive feedback mechanism.

• 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. Fulltekst i vitenarkiv 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.

• 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. 7:8206, s. 1–14. doi: 10.1038/s41598-017-08586-7. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• 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. 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. 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. 7(1). doi: 10.1038/s41598-017-12662-3. Fulltekst i vitenarkiv
• 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 Vis sammendrag

  Adjusting the thickness and internodal length of the myelin sheath is a mechanism for tuning the conduction velocity of axons to match computational needs. Interactions between oligodendrocyte precursor cells (OPCs) and developing axons regulate the formation of myelin around axons. We now show, using organotypic cerebral cortex slices from mice expressing eGFP in Sox10‐positive oligodendrocytes, that endogenously released GABA, acting on GABAA receptors, greatly reduces the number of oligodendrocyte lineage cells. The decrease in oligodendrocyte number correlates with a reduction in the amount of myelination but also an increase in internode length, a parameter previously thought to be set by the axon diameter or to be a property intrinsic to oligodendrocytes. Importantly, while TTX block of neuronal activity had no effect on oligodendrocyte lineage cell number when applied alone, it was able to completely abolish the effect of blocking GABAA receptors, suggesting that control of myelination by endogenous GABA may require a permissive factor to be released from axons. In contrast, block of AMPA/KA receptors had no effect on oligodendrocyte lineage cell number or myelination. These results imply that, during development, GABA can act as a local environmental cue to control myelination and thus influence the conduction velocity of action potentials within the CNS. GLIA 2017;65:309–321

• 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. Fulltekst i vitenarkiv 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.

• 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. Fulltekst i vitenarkiv
• Lauritzen, Knut Husø; Hasan-Olive, Md Mahdi; Regnell, Christine E; Kleppa, Liv; Knudsen, Morten Scheibye & 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. 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 Vis sammendrag

  Glia-neuron partnership is important for inner retinal homeostasis and any disturbances may result in retinal ganglion cell (RGC) death. Müller cells support RGCs with essential functions such as removing excess glutamate and providing energy sources. The aim was to explore the impact of Müller cells on RGC survival. To investigate the Müller cell/RGC interactions we developed a coculture model, in which primary Müller cells were grown in inserts on top of pure primary RGC cultures. The impact of starvation and mitochondrial inhibition on the Müller cell ability to protect RGCs was studied. Moreover, the ability of Müller cells to remove glutamate from the extracellular space was investigated. RGC survival was evaluated by cell viability assays and glutamate uptake was assessed by kinetic uptake assays. We demonstrated a significantly increased RGC survival in presence of untreated and prestarved Müller cells. Additionally, prestarved Müller cells significantly increased RGC survival after mitochondrial inhibition. Finally, we revealed a significantly increased ability to take up glutamate in starved Müller cells. Overall, our study confirms essential roles of Müller cells in RGC survival. We suggest that targeting Müller cell function could have potential for future treatment strategies to prevent blinding neurodegenerative retinal diseases.

• 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. Fulltekst i vitenarkiv
• Holm-Hansen, Signe; Low, J.K.; Zieba, J; Gjedde, A.; Bergersen, Linda Hildegard & Karl, Tim (2015). 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. Fulltekst i vitenarkiv 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.

• 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv 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.

• 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• Mariga, Shelton T.; Kolko, Miriam; Gjedde, Albert & Bergersen, Linda Hildegard (2014). Lactate transport and receptor actions in cerebral malaria. Frontiers in Neuroenergetics. 6(MAY). doi: 10.3389/fnins.2014.00125. Fulltekst i vitenarkiv Vis sammendrag

  Cerebral malaria (CM), caused by Plasmodium falciparum infection, is a prevalent neurological disorder in the tropics. Most of the patients are children, typically with intractable seizures and high mortality. Current treatment is unsatisfactory. Understanding the pathogenesis of CM is required in order to identify therapeutic targets. Here, we argue that cerebral energy metabolic defects are probable etiological factors in CM pathogenesis, because malaria parasites consume large amounts of glucose metabolized mostly to lactate. Monocarboxylate transporters (MCTs) mediate facilitated transfer, which serves to equalize lactate concentrations across cell membranes in the direction of the concentration gradient. The equalizing action of MCTs is the basis for lactate’s role as a volume transmitter of metabolic signals in the brain. Lactate binds to the lactate receptor GPR81, recently discovered on brain cells and cerebral blood vessels, causing inhibition of adenylyl cyclase. High levels of lactate delivered by the parasite at the vascular endothelium may damage the blood–brain barrier, disrupt lactate homeostasis in the brain, and imply MCTs and the lactate receptor as novel therapeutic targets in CM.

• 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. Fulltekst i vitenarkiv
• Scheibye, Morten Knudsen; 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• Eid, Tore; Lee, Tih-Shih W.; Wang, Yue; Perez, Edgar; Drummond, Jana & Lauritzen, Fredrik [Vis alle 11 forfattere av denne artikkelen] (2013). Gene expression of glutamate metabolizing enzymes in the hippocampal formation in human temporal lobe epilepsy. Epilepsia. ISSN 0013-9580. 54(2), s. 228–238. doi: 10.1111/epi.12008. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• 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. doi: 10.3389/fnene.2013.00007. Fulltekst i vitenarkiv 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. Fulltekst i vitenarkiv 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard; Bramham, Clive R.; Hugdahl, Kenneth; Sander, Miriam & Storm-Mathisen, Jon (2013). The changing brain – Insights into the mechanisms of neural and behavioral adaptation to the environment. Neuroscience. ISSN 0306-4522. 247, s. 412–422. doi: 10.1016/j.neuroscience.2013.04.012. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Fang, Fei; Bergersen, Linda Hildegard & Gilmour, Brian Christopher (2023). Molecular, Cellular, and Metabolic Fundamentals of Human Aging. Academic Press. ISBN 9780323916172. 246 s. Fulltekst i vitenarkiv
• 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 9788299501040. 30 s. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2013). Brain Energy 2013 – Current Advances in Brain Maintenance. DNVA: www.dnva.no/binfil/download.php?tid=58301. ISBN 9788299501026. 18 s. Fulltekst i vitenarkiv

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• Wang, Heling; Siow, Richard; Schmauck-Medina, Tomás Alejandro; 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), s. 1–10. doi: 10.1093/gerona/glae029. Fulltekst i vitenarkiv Vis sammendrag

  Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a “Money Follows Cooperation agreement” between the 2 nations. The inaugural Norway–UK joint meeting on aging and dementia gathered leading experts on aging and dementia from the 2 nations to share their latest discoveries in related fields. Since aging is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular aging mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (eg, using NAD+ precursors). The meeting facilitated dialogue among policymakers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy aging.

• Bergersen, Linda Hildegard; Petersen, Fernanda Cristina & Dahle, Ulf R (2020). Kort sagt, fredag 27. mars. [Journal]. Aftenposten. Fulltekst i vitenarkiv
• 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? 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] (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. 8(1), s. 4245–4245. doi: 10.1038/s41598-018-20586-9. Fulltekst i vitenarkiv
• 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 (Tidsskriftet). ISSN 0029-2001. 137, s. 14–15. doi: 10.4045/tidsskr.17.0487. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv 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. Fulltekst i vitenarkiv 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.

• Bergersen, Linda Hildegard (2016). Hvor ligger forskningsfronten innen demens nå? Hva vet vi og hva vet vi ikke? Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2016). "Lactate transport and receptor action in the brain: rescue of cognitive decline”. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2016). The brain has a lactate receptor. Fulltekst i vitenarkiv
• Moretti, Laura; Stølen, Tomas; Wisløff, Ulrik; Storm-Mathisen, Jon; Bergersen, Linda Hildegard & Morland, Cecilie (2016). Effects of intrinsic fitness level on mitochondria during exercise. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2016). Novel mechanism for exercise‐induced angiogenesis in the brain. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2016). The lactate receptor is important for brain vascularization. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2016). Exercise induces brain VEGFA and angiogenesis through the lactate receptor. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• 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 9781493923120. s. 281–297. doi: 10.1007/978-1-4939-2313-7_15. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2015). Exercise in healthy aging. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2015). Lactate transport and signaling in the brain: potential therapeutic targets and roles in body-brain interaction. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2015). Clinical use of lactate monitoring in malaria. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2015). Gir melkesyre bedre hjernehelse? Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2015). Lactate Transport and Signaling in the Brain: Potential Therapeutic Targets and Roles in Body-Brain Interaction. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2015). Monocarboxylate transporters and lactate receptor expression and function in the brain. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2015). Lactate transport and receptor actions in cerebral malaria. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2014). I FORM ekspert med spesiale: Sunn aldring. [Internet]. iFORM.nu. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2014). Professor i fysiologi, ekspert i sund aldring. [Internet]. iform.dk - advisory-board. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2014). Mutasjon i transportørgen kan gi ketoacidose. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 134(23/24), s. 2257–2257. doi: 10.4045/tidsskr.14.1326. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2014). Professor i fysiologi och expert på sunt åldrande. [Internet]. iform.se - expertpanelen. Fulltekst i vitenarkiv
• 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. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2014). Lactate receptor in the brain. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2014). A ketogenic diet accelerates neurodegeneration in forebrain neurons during mitochondrial DNA toxicity. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2014). The brain lactate receptor – does it matter in cognitive impairment. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2014). Lactate as messenger in the CNS. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2014). Trening for et bedre og lengre liv - Hjerne og trening. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2014). Trening for hjernehelse. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2013). Laktat har signalfunksjon i hjernen. [Journal]. Tidsskrift for Den norske legeforening. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2013). Lactate is a volume transmitter – 'New Deal' for understanding brain function and brain disease. Fulltekst i vitenarkiv
• Bergersen, Linda Hildegard (2013). Lactate receptor in the Brain. Fulltekst i vitenarkiv

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