Neurochemical Research

, Volume 44, Issue 1, pp 22–37 | Cite as

A Ketogenic Diet Improves Mitochondrial Biogenesis and Bioenergetics via the PGC1α-SIRT3-UCP2 Axis

  • Md Mahdi Hasan-OliveEmail author
  • Knut H. Lauritzen
  • Mohammad Ali
  • Lene Juel Rasmussen
  • Jon Storm-Mathisen
  • Linda H. BergersenEmail author
Original Paper


A ketogenic diet (KD; high-fat, low-carbohydrate) can benefit refractory epilepsy, but underlying mechanisms are unknown. We used mice inducibly expressing a mutated form of the mitochondrial DNA repair enzyme UNG1 (mutUNG1) to cause progressive mitochondrial dysfunction selectively in forebrain neurons. We examined the levels of mRNAs and proteins crucial for mitochondrial biogenesis and dynamics. We show that hippocampal pyramidal neurons in mutUNG1 mice, as well as cultured rat hippocampal neurons and human fibroblasts with H2O2 induced oxidative stress, improve markers of mitochondrial biogenesis, dynamics and function when fed on a KD, and when exposed to the ketone body β-hydroxybutyrate, respectively, by upregulating PGC1α, SIRT3 and UCP2, and (in cultured cells) increasing the oxygen consumption rate (OCR) and the NAD+/NADH ratio. The mitochondrial level of UCP2 was significantly higher in the perikarya and axon terminals of hippocampus CA1 pyramidal neurons in KD treated mutUNG1 mice compared with mutUNG1 mice fed a standard diet. The β-hydroxybutyrate receptor GPR109a (HCAR2), but not the structurally closely related lactate receptor GPR81 (HCAR1), was upregulated in mutUNG1 mice on a KD, suggesting a selective influence of KD on ketone body receptor mechanisms. We conclude that progressive mitochondrial dysfunction in mutUNG1 expressing mice causes oxidative stress, and that exposure of animals to KD, or of cells to ketone body in vitro, elicits compensatory mechanisms acting to augment mitochondrial mass and bioenergetics via the PGC1α-SIRT3-UCP2 axis (The compensatory processes are overwhelmed in the mutUNG1 mice by all the newly formed mitochondria being dysfunctional).


Ketogenic diet MutUNG1 Biogenesis Bioenergetics 



This study was supported by research Grants from the Research Council of Norway, the Norwegian Health Association, and the Lundbeck Foundation (Denmark).

Compliance with Ethical Standards

Conflict of interest

The authors have no actual or potential conflicts of interest. All aspects of the research described here were carried out in accordance with the laws of Norway concerning animal research.

Supplementary material

11064_2018_2588_MOESM1_ESM.pdf (181 kb)
Supplementary material 1 (PDF 180 KB)


  1. 1.
    Kann O, Kovacs R (2007) Mitochondria and neuronal activity. Am J Physiol Cell Physiol 292:C641–C657CrossRefGoogle Scholar
  2. 2.
    Yang Y, Ouyang Y, Yang L, Beal MF, McQuibban A, Vogel H, Lu B (2008) Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc Natl Acad Sci USA 105:7070–7075CrossRefGoogle Scholar
  3. 3.
    Richter C, Park JW, Ames BN (1988) Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci USA 85:6465–6467CrossRefGoogle Scholar
  4. 4.
    Larsen NB, Rasmussen M, Rasmussen LJ (2005) Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 5:89–108CrossRefGoogle Scholar
  5. 5.
    Wallace DC (1994) Mitochondrial DNA sequence variation in human evolution and disease. Proc Natl Acad Sci USA 91:8739–8746CrossRefGoogle Scholar
  6. 6.
    Anderson CT, Friedberg EC (1980) The presence of nuclear and mitochondrial uracil-DNA glycosylase in extracts of human KB cells. Nucleic Acids Res 8:875–888CrossRefGoogle Scholar
  7. 7.
    Cervenka MC, Henry B, Nathan J, Wood S, Volek JS (2013) Worldwide dietary therapies for adults with epilepsy and other disorders. J Child Neurol 28:1034–1040CrossRefGoogle Scholar
  8. 8.
    Kessler SK, Neal EG, Camfield CS, Kossoff EH (2011) Dietary therapies for epilepsy: future research. Epilepsy Behav 22:17–22CrossRefGoogle Scholar
  9. 9.
    Kossoff EH, Zupec-Kania BA, Rho JM (2009) Ketogenic diets: an update for child neurologists. J Child Neurol 24:979–988CrossRefGoogle Scholar
  10. 10.
    Levy R, Cooper P (2003) Ketogenic diet for epilepsy. Cochrane Database Syst Rev 2003:CD001903Google Scholar
  11. 11.
    Levy RG, Cooper PN, Giri P (2012) Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev. Google Scholar
  12. 12.
    Villeneuve N, Pinton F, Bahi-Buisson N, Dulac O, Chiron C, Nabbout R (2009) The ketogenic diet improves recently worsened focal epilepsy. Dev Med Child Neurol 51:276–281CrossRefGoogle Scholar
  13. 13.
    Ruskin DN, Svedova J, Cote JL, Sandau U, Rho JM, Kawamura M Jr, Boison D, Masino SA (2013) Ketogenic diet improves core symptoms of autism in BTBR mice. PLoS ONE 8:e65021CrossRefGoogle Scholar
  14. 14.
    Zhao Z, Lange DJ, Voustianiouk A, MacGrogan D, Ho L, Suh J, Humala N, Thiyagarajan M, Wang J, Pasinetti GM (2006) A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci 7:29CrossRefGoogle Scholar
  15. 15.
    Ruskin DN, Ross JL, Kawamura M Jr, Ruiz TL, Geiger JD, Masino SA (2011) A ketogenic diet delays weight loss and does not impair working memory or motor function in the R6/2 1J mouse model of Huntington’s disease. Physiol Behav 103:501–507CrossRefGoogle Scholar
  16. 16.
    Van der Auwera I, Wera S, Van Leuven F, Henderson ST (2005) A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr Metab 2:28CrossRefGoogle Scholar
  17. 17.
    Vanitallie TB, Nonas C, Di Rocco A, Boyar K, Hyams K, Heymsfield SB (2005) Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study. Neurology 64:728–730CrossRefGoogle Scholar
  18. 18.
    Hartman AL, Vining EP (2007) Clinical aspects of the ketogenic diet. Epilepsia 48:31–42CrossRefGoogle Scholar
  19. 19.
    Nordi DR, De Vivo DC (2004) Effects of the ketogenic diet on cerebral energy metabolism. In: Stafstrom CE, Rho JM (eds) Epilepsy and the ketogenic diet, 1st edn. Humana Press, Totowa, pp 179–184CrossRefGoogle Scholar
  20. 20.
    Yudkoff M, Daikhin Y, Nissim I, Nissim I (2004) The ketogenic diet: interactions with brain amino acid handling. In: Stafstrom CE, Rho JM (eds) Epilepsy and the ketogenic diet, 1st edn. Humana Press, Totowa, pp 185–200CrossRefGoogle Scholar
  21. 21.
    Newman JC, Covarrubias AJ, Zhao M, Yu X, Gut P, Ng CP, Huang Y, Haldar S, Verdin E (2017) Ketogenic diet reduces midlife mortality and improves memory in aging mice. Cell Metab 26:547–557.e548CrossRefGoogle Scholar
  22. 22.
    Roberts MN, Wallace MA, Tomilov AA, Zhou Z, Marcotte GR, Tran D, Perez G, Gutierrez-Casado E, Koike S, Knotts TA, Imai DM, Griffey SM, Kim K, Hagopian K, Haj FG, Baar K, Cortopassi GA, Ramsey JJ, Lopez-Dominguez JA (2017) A ketogenic diet extends longevity and healthspan in adult mice. Cell Metab 26:539–546.e535CrossRefGoogle Scholar
  23. 23.
    Halestrap AP, Meredith D (2004) The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 447:619–628CrossRefGoogle Scholar
  24. 24.
    Forero-Quintero LS, Deitmer JW, Becker HM (2017) Reduction of epileptiform activity in ketogenic mice: the role of monocarboxylate transporters. Sci Rep 7:4900CrossRefGoogle Scholar
  25. 25.
    Nedergaard J, Cannon B (2003) The ‘novel’ ‘uncoupling’ proteins UCP2 and UCP3: what do they really do? Pros and cons for suggested functions. Exp Physiol 88:65–84CrossRefGoogle Scholar
  26. 26.
    Sullivan PG, Rippy NA, Dorenbos K, Concepcion RC, Agarwal AK, Rho JM (2004) The ketogenic diet increases mitochondrial uncoupling protein levels and activity. Ann Neurol 55:576–580CrossRefGoogle Scholar
  27. 27.
    Korshunov SS, Skulachev VP, Starkov AA (1997) High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 416:15–18CrossRefGoogle Scholar
  28. 28.
    Pecqueur C, Alves-Guerra MC, Gelly C, Levi-Meyrueis C, Couplan E, Collins S, Ricquier D, Bouillaud F, Miroux B (2001) Uncoupling protein 2, in vivo distribution, induction upon oxidative stress, and evidence for translational regulation. J Biol Chem 276:8705–8712CrossRefGoogle Scholar
  29. 29.
    Diano S, Matthews RT, Patrylo P, Yang L, Beal MF, Barnstable CJ, Horvath TL (2003) Uncoupling protein 2 prevents neuronal death including that occurring during seizures: a mechanism for preconditioning. Endocrinology 144:5014–5021CrossRefGoogle Scholar
  30. 30.
    Toda C, Diano S (2014) Mitochondrial UCP2 in the central regulation of metabolism. Best Pract Res Clin Endocrinol Metab 28:757–764CrossRefGoogle Scholar
  31. 31.
    Bechmann I, Diano S, Warden CH, Bartfai T, Nitsch R, Horvath TL (2002) Brain mitochondrial uncoupling protein 2 (UCP2): a protective stress signal in neuronal injury. Biochem Pharmacol 64:363–367CrossRefGoogle Scholar
  32. 32.
    Conti B, Sanchez-Alavez M, Winsky-Sommerer R, Morale MC, Lucero J, Brownell S, Fabre V, Huitron-Resendiz S, Henriksen S, Zorrilla EP, de Lecea L, Bartfai T (2006) Transgenic mice with a reduced core body temperature have an increased life span. Science 314:825–828CrossRefGoogle Scholar
  33. 33.
    Fridell YW, Sanchez-Blanco A, Silvia BA, Helfand SL (2005) Targeted expression of the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly. Cell Metab 1:145–152CrossRefGoogle Scholar
  34. 34.
    Hirose M, Schilf P, Lange F, Mayer J, Reichart G, Maity P, Johren O, Schwaninger M, Scharffetter-Kochanek K, Sina C, Sadik CD, Kohling R, Miroux B, Ibrahim SM (2016) Uncoupling protein 2 protects mice from aging. Mitochondrion 30:42–50CrossRefGoogle Scholar
  35. 35.
    Andrews ZB, Horvath B, Barnstable CJ, Elsworth J, Yang L, Beal MF, Roth RH, Matthews RT, Horvath TL (2005) Uncoupling protein-2 is critical for nigral dopamine cell survival in a mouse model of Parkinson’s disease. J Neurosci 25:184–191CrossRefGoogle Scholar
  36. 36.
    Conti B, Sugama S, Lucero J, Winsky-Sommerer R, Wirz SA, Maher P, Andrews Z, Barr AM, Morale MC, Paneda C, Pemberton J, Gaidarova S, Behrens MM, Beal F, Sanna PP, Horvath T, Bartfai T (2005) Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6-methyl-phenyl-tetrahydropyridine toxicity. J Neurochem 93:493–501CrossRefGoogle Scholar
  37. 37.
    Mattiasson G, Shamloo M, Gido G, Mathi K, Tomasevic G, Yi S, Warden CH, Castilho RF, Melcher T, Gonzalez-Zulueta M, Nikolich K, Wieloch T (2003) Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nat Med 9:1062–1068CrossRefGoogle Scholar
  38. 38.
    Bough K (2008) Energy metabolism as part of the anticonvulsant mechanism of the ketogenic diet. Epilepsia 49(Suppl 8):91–93CrossRefGoogle Scholar
  39. 39.
    Srivastava S, Baxa U, Niu G, Chen X, Veech RL (2013) A ketogenic diet increases brown adipose tissue mitochondrial proteins and UCP1 levels in mice. IUBMB Life 65:58–66CrossRefGoogle Scholar
  40. 40.
    Hutfles LJ, Wilkins HM, Koppel SJ, Weidling IW, Selfridge JE, Tan E, Thyfault JP, Slawson C, Fenton AW, Zhu H, Swerdlow RH (2017) A bioenergetics systems evaluation of ketogenic diet liver effects. Appl Physiol Nutr Metab 42:955–962CrossRefGoogle Scholar
  41. 41.
    Yin J, Han P, Tang Z, Liu Q, Shi J (2015) Sirtuin 3 mediates neuroprotection of ketones against ischemic stroke. J Cereb Blood Flow Metab 35:1783–1789CrossRefGoogle Scholar
  42. 42.
    Rardin MJ, Newman JC, Held JM, Cusack MP, Sorensen DJ, Li B, Schilling B, Mooney SD, Kahn CR, Verdin E, Gibson BW (2013) Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways. Proc Natl Acad Sci USA 110:6601–6606CrossRefGoogle Scholar
  43. 43.
    Pagel-Langenickel I, Bao J, Joseph JJ, Schwartz DR, Mantell BS, Xu X, Raghavachari N, Sack MN (2008) PGC-1alpha integrates insulin signaling, mitochondrial regulation, and bioenergetic function in skeletal muscle. J Biol Chem 283:22464–22472CrossRefGoogle Scholar
  44. 44.
    Lomb DJ, Laurent G, Haigis MC (2010) Sirtuins regulate key aspects of lipid metabolism. Biochim Biophys Acta 1804:1652–1657CrossRefGoogle Scholar
  45. 45.
    Ansari A, Rahman MS, Saha SK, Saikot FK, Deep A, Kim KH (2017) Function of the SIRT3 mitochondrial deacetylase in cellular physiology, cancer, and neurodegenerative disease. Aging Cell 16:4–16CrossRefGoogle Scholar
  46. 46.
    Su J, Liu J, Yan XY, Zhang Y, Zhang JJ, Zhang LC, Sun LK (2017) Cytoprotective effect of the UCP2-SIRT3 signaling pathway by decreasing mitochondrial oxidative stress on cerebral ischemia-reperfusion injury. Int J Mol Sci 18Google Scholar
  47. 47.
    Lauritzen KH, Moldestad O, Eide L, Carlsen H, Nesse G, Storm JF, Mansuy IM, Bergersen LH, Klungland A (2010) Mitochondrial DNA toxicity in forebrain neurons causes apoptosis, neurodegeneration, and impaired behavior. Mol Cell Biol 30:1357–1367CrossRefGoogle Scholar
  48. 48.
    Dianov GL, Sleeth KM, Dianova II, Allinson SL (2003) Repair of abasic sites in DNA. Mutat Res 531:157–163CrossRefGoogle Scholar
  49. 49.
    Pinz KG, Shibutani S, Bogenhagen DF (1995) Action of mitochondrial DNA polymerase gamma at sites of base loss or oxidative damage. J Biol Chem 270:9202–9206CrossRefGoogle Scholar
  50. 50.
    Lauritzen KH, Dalhus B, Storm JF, Bjoras M, Klungland A (2011) Modeling the impact of mitochondrial DNA damage in forebrain neurons and beyond. Mech Ageing Dev 132:424–428CrossRefGoogle Scholar
  51. 51.
    Loeb LA, Wallace DC, Martin GM (2005) The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtDNA mutations. Proc Natl Acad Sci USA 102:18769–18770CrossRefGoogle Scholar
  52. 52.
    Nicholls DG (2008) Oxidative stress and energy crises in neuronal dysfunction. Ann NY Acad Sci 1147:53–60CrossRefGoogle Scholar
  53. 53.
    Lauritzen KH, Hasan-Olive MM, Regnell CE, Kleppa L, Scheibye-Knudsen M, Gjedde A, Klungland A, Bohr VA, Storm-Mathisen J, Bergersen LH (2016) A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain. Neurobiol Aging 48:34–47CrossRefGoogle Scholar
  54. 54.
    Bergersen LH, Storm-Mathisen J, Gundersen V (2008) Immunogold quantification of amino acids and proteins in complex subcellular compartments. Nat Protoc 3:144–152CrossRefGoogle Scholar
  55. 55.
    Marosi K, Kim SW, Moehl K, Scheibye-Knudsen M, Cheng A, Cutler R, Camandola S, Mattson MP (2016) 3-Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons. J Neurochem 139:769–781CrossRefGoogle Scholar
  56. 56.
    Reddy PH, Shirendeb UP (2012) Mutant huntingtin, abnormal mitochondrial dynamics, defective axonal transport of mitochondria, and selective synaptic degeneration in Huntington’s disease. Biochim Biophys Acta 1822:101–110CrossRefGoogle Scholar
  57. 57.
    Wang Q, Zhang M, Liang B, Shirwany N, Zhu Y, Zou MH (2011) Activation of AMP-activated protein kinase is required for berberine-induced reduction of atherosclerosis in mice: the role of uncoupling protein 2. PLoS ONE 6:e25436CrossRefGoogle Scholar
  58. 58.
    Coyle CH, Kader KN (2007) Mechanisms of H2O2-induced oxidative stress in endothelial cells exposed to physiologic shear stress. ASAJO J 53:17–22CrossRefGoogle Scholar
  59. 59.
    Olichon A, Guillou E, Delettre C, Landes T, Arnaune-Pelloquin L, Emorine LJ, Mils V, Daloyau M, Hamel C, Amati-Bonneau P, Bonneau D, Reynier P, Lenaers G, Belenguer P (2006) Mitochondrial dynamics and disease, OPA1. Biochim Biophys Acta 1763:500–509CrossRefGoogle Scholar
  60. 60.
    Lu B (2009) Mitochondrial dynamics and neurodegeneration. Curr Neurol Neurosci Rep 9:212–219CrossRefGoogle Scholar
  61. 61.
    Kuei C, Yu J, Zhu J, Wu J, Zhang L, Shih A, Mirzadegan T, Lovenberg T, Liu C (2011) Study of GPR81, the lactate receptor, from distant species identifies residues and motifs critical for GPR81 functions. Mol Pharmacol 80:848–858CrossRefGoogle Scholar
  62. 62.
    Richard D, Clavel S, Huang Q, Sanchis D, Ricquier D (2001) Uncoupling protein 2 in the brain: distribution and function. Biochem Soc Trans 29:812–817CrossRefGoogle Scholar
  63. 63.
    Simuni T, Sethi K (2008) Nonmotor manifestations of Parkinson’s disease. Ann Neurol 64(Suppl 2):S65–S80Google Scholar
  64. 64.
    Ahola-Erkkila S, Carroll CJ, Peltola-Mjosund K, Tulkki V, Mattila I, Seppanen-Laakso T, Oresic M, Tyynismaa H, Suomalainen A (2010) Ketogenic diet slows down mitochondrial myopathy progression in mice. Hum Mol Genet 19:1974–1984CrossRefGoogle Scholar
  65. 65.
    Al-Zaid NS, Dashti HM, Mathew TC, Juggi JS (2007) Low carbohydrate ketogenic diet enhances cardiac tolerance to global ischaemia. Acta Cardiol 62:381–389CrossRefGoogle Scholar
  66. 66.
    Bough KJ, Wetherington J, Hassel B, Pare JF, Gawryluk JW, Greene JG, Shaw R, Smith Y, Geiger JD, Dingledine RJ (2006) Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol 60:223–235CrossRefGoogle Scholar
  67. 67.
    Kim DK, Heineman FW, Balaban RS (1991) Effects of beta-hydroxybutyrate on oxidative metabolism and phosphorylation potential in canine heart in vivo. Am J Physiol 260:H1767–H1773Google Scholar
  68. 68.
    Tieu K, Perier C, Caspersen C, Teismann P, Wu DC, Yan SD, Naini A, Vila M, Jackson-Lewis V, Ramasamy R, Przedborski S (2003) D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J Clin Invest 112:892–901CrossRefGoogle Scholar
  69. 69.
    Sampson M, Lathen D, Dallon B, Draney C, Ray J, Kener K, Parker B, Witt J, Gibbs J, Tessem JS, Bikman BT (2017) Beta-hydroxybutyrate favorably alters b-cell survival and mitochondrial bioenergetics. FASEB J 31:883.888Google Scholar
  70. 70.
    Masuda R, Monahan JW, Kashiwaya Y (2005) D-beta-hydroxybutyrate is neuroprotective against hypoxia in serum-free hippocampal primary cultures. J Neurosci Res 80:501–509CrossRefGoogle Scholar
  71. 71.
    Jornayvaz FR, Jurczak MJ, Lee HY, Birkenfeld AL, Frederick DW, Zhang D, Zhang XM, Samuel VT, Shulman GI (2010) A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain. Am J Physiol Endocrinol Metab 299:E808–E815CrossRefGoogle Scholar
  72. 72.
    Chan DC (2006) Mitochondrial fusion and fission in mammals. Annu Rev Cell Dev Biol 22:79–99CrossRefGoogle Scholar
  73. 73.
    Chen H, Chan DC (2006) Critical dependence of neurons on mitochondrial dynamics. Curr Opin Cell Biol 18:453–459CrossRefGoogle Scholar
  74. 74.
    Brenmoehl J, Hoeflich A (2013) Dual control of mitochondrial biogenesis by sirtuin 1 and sirtuin 3. Mitochondrion 13:755–761CrossRefGoogle Scholar
  75. 75.
    Shimazu T, Hirschey MD, Hua L, Dittenhafer-Reed KE, Schwer B, Lombard DB, Li Y, Bunkenborg J, Alt FW, Denu JM, Jacobson MP, Verdin E (2010) SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production. Cell Metab 12:654–661CrossRefGoogle Scholar
  76. 76.
    Liu J, Li D, Zhang T, Tong Q, Ye RD, Lin L (2017) SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and mitochondrial integrity. Cell Death Dis 8:e3158CrossRefGoogle Scholar
  77. 77.
    Ding Y, Yang H, Wang Y, Chen J, Ji Z, Sun H (2017) Sirtuin 3 is required for osteogenic differentiation through maintenance of PGC-1a-SOD2-mediated regulation of mitochondrial function. Int J Biol Sci 13:254–264CrossRefGoogle Scholar
  78. 78.
    Elamin M, Ruskin DN, Masino SA, Sacchetti P (2017) Ketone-based metabolic therapy: is increased NAD(+) a primary mechanism? Front Mol Neurosci 10:377CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Synaptic Neurochemistry and Amino Acid Transporter Laboratory, Division of Anatomy and CMBN/SERTA Healthy Brain Ageing Center, Institute of Basic Medical SciencesUniversity of OsloOsloNorway
  2. 2.Brain and Muscle Energy Group, Electron Microscopy Laboratory, Institute of Oral BiologyUniversity of OsloOsloNorway
  3. 3.Center for Healthy Aging, Department of Neurosciences and Pharmacology, Faculty of Health SciencesUniversity of CopenhagenCopenhagenDenmark
  4. 4.Research Institute of Internal MedicineOslo University Hospital RikshospitaletOsloNorway
  5. 5.Department of BiochemistrySir Salimullah Medical College & Mitford HospitalDhakaBangladesh

Personalised recommendations