Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β- hydroxybutyrate

eLife

Volumn 5, Issue JUN2016, 2016, Pages

  Sleiman, Sama F ^a   Henry, Jeffrey ^b,c,d   Al Haddad, Rami ^a   El Hayek, Lauretta ^a   Haidar, Edwina Abou ^a   Stringer, Thomas ^b,c,d   Ulja, Devyani ^b,c,d   Karuppagounder, Saravanan S ^e,f   Holson, Edward B ^g,h   Ratan, Rajiv R ^e,f   Ninan, Ipe ^b,c,d   Chao, Moses V ^b,c,d  

^a LEBANESE AMERICAN UNIVERSITY   (Lebanon)

^b NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c NEW YORK UNIVERSITY   (United States)

^d NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

^e BURKE MEDICAL RESEARCH INSTITUTE   (United States)

^f Department of Molecular Biology and Genetics   (United States)

^g BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^h 400 Technology Square   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXYBUTYRIC ACID; BRAIN DERIVED NEUROTROPHIC FACTOR; GLUCOSE; HISTONE DEACETYLASE 2; HISTONE DEACETYLASE 3; KETONE BODY; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; BRAIN DERIVED NEUROTROPHIC FACTOR RECEPTOR; HDAC2 PROTEIN, MOUSE; HISTONE; HISTONE DEACETYLASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; ELECTROPHYSIOLOGY; EXCITATORY POSTSYNAPTIC POTENTIAL; EXERCISE; GENE SILENCING; HIPPOCAMPUS; IMMUNOBLOTTING; IMMUNOPRECIPITATION; MALE; MOUSE; MUS MUSCULUS; NEUROTRANSMITTER RELEASE; NONHUMAN; PROMOTER REGION; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; ACETYLATION; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CELL CULTURE; CHEMISTRY; CYTOLOGY; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; NERVE CELL;

3-HYDROXYBUTYRIC ACID; ACETYLATION; ANIMALS; BRAIN-DERIVED NEUROTROPHIC FACTOR; CELLS, CULTURED; GENE EXPRESSION REGULATION; HIPPOCAMPUS; HISTONE DEACETYLASE 2; HISTONE DEACETYLASES; HISTONES; MALE; MICE; MICE, INBRED C57BL; NEURONS; NEUROTRANSMITTER AGENTS; PHYSICAL CONDITIONING, ANIMAL; RECEPTOR, TRKB;

EID: 84975321438     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.15092     Document Type: Article

References (53)

1. Aguiar AS, Castro AA, Moreira EL, Glaser V, Santos AR, Tasca CI, Latini A, Prediger RD. 2011. Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats: involvement of hippocampal plasticity via AKT, CREB and BDNF signaling. Mechanisms of Ageing and Development 132: 560-567. doi: 10.1016/j.mad.2011.09.005
2. Albrecht E, Norheim F, Thiede B, Holen T, Ohashi T, Schering L, Lee S, Brenmoehl J, Thomas S, Drevon CA, Erickson HP, Maak S. 2015. Irisin - a myth rather than an exercise-inducible myokine. Scientific Reports 5. doi: 10.1038/srep08889
3. Alsina B, Vu T, Cohen-Cory S. 2001. Visualizing synapse formation in arborizing optic axons in vivo: dynamics and modulation by BDNF. Nature Neuroscience 4: 1093-1101. doi: 10.1038/nn735
4. Autry AE, Monteggia LM. 2012. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacological Reviews 64: 238-258. doi: 10.1124/pr.111.005108
5. Barton KM, Archin NM, Keedy KS, Espeseth AS, Zhang YL, Gale J, Wagner FF, Holson EB, Margolis DM. 2014. Selective HDAC inhibition for the disruption of latent HIV-1 infection. PloS One 9: e102684. doi: 10.1371/journal.pone.0102684
6. Berg MM, Sternberg DW, Parada LF, Chao MV. 1992. K-252a inhibits nerve growth factor-induced trk proto-oncogene tyrosine phosphorylation and kinase activity. The Journal of Biological Chemistry 267: 13-16.
7. Bibel M, Barde YA. 2000. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes & Development 14: 2919-2937. doi: 10.1101/gad.841400
8. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Boström EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Højlund K, Gygi SP, Spiegelman BM. 2012. A PGC1-a-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481: 463-468. doi: 10.1038/nature10777
9. Chen B, Ma XL, Geng Z, Huang SH, Zhai LK, Guo YY, Chen ZY. 2015. Up-regulation of c-Jun NH2-terminal kinase-interacting protein 3 (JIP3) contributes to BDNF-enhanced neurotransmitter release. Journal of Neurochemistry 135: 453-465. doi: 10.1111/jnc.13226
10. Cotman CW, Berchtold NC, Christie LA. 2007. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends in Neurosciences 30: 464-472. doi: 10.1016/j.tins.2007.06.011
11. Crabb DP, Smith ND, Zhu H, Nielson KA, Woodard JL, Seidenberg M, Durgerian S, Hazlett KE, Figueroa CM, Kandah CC, Kay CD, Matthews MA. 2014. What’s on TV? Detecting age-related neurodegenerative eye disease using eye movement scanpaths. Frontiers in Aging Neuroscience 6. doi: 10.3389/fnagi.2014.00312
12. Duman RS, Monteggia LM. 2006. A neurotrophic model for stress-related mood disorders. Biological Psychiatry 59: 1116-1127. doi: 10.1016/j.biopsych.2006.02.013
13. Frazzitta G, Maestri R, Ghilardi MF, Riboldazzi G, Perini M, Bertotti G, Boveri N, Buttini S, Lombino FL, Uccellini D, Turla M, Pezzoli G, Comi C. 2014. Intensive rehabilitation increases BDNF serum levels in parkinsonian patients: a randomized study. Neurorehabilitation and Neural Repair 28: 163-168. doi: 10.1177/1545968313508474
14. Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, Gao J, Nieland TJ, Zhou Y, Wang X, Mazitschek R, Bradner JE, DePinho RA, Jaenisch R, Tsai LH. 2009. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459: 55-60. doi: 10.1038/nature07925
15. Haberland M, Montgomery RL, Olson EN. 2009. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nature Reviews 10: 32-42. doi: 10.1038/nrg2485
16. Isackson PJ, Huntsman MM, Murray KD, Gall CM. 1991. BDNF mRNA expression is increased in adult rat forebrain after limbic seizures: temporal patterns of induction distinct from NGF. Neuron 6: 937-948. doi: 10.1016/0896-6273(91)90234-Q
17. Jedrychowski MP, Wrann CD, Paulo JA, Gerber KK, Szpyt J, Robinson MM, Nair KS, Gygi SP, Spiegelman BM. 2015. Detection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry. Cell Metabolism 22: 734-740. doi: 10.1016/j.cmet.2015.08.001
18. Jovanovic JN, Czernik AJ, Fienberg AA, Greengard P, Sihra TS. 2000. Synapsins as mediators of BDNF-enhanced neurotransmitter release. Nature Neuroscience 3: 323-329. doi: 10.1038/73888
19. Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL. 2000. D-beta-hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease. Proceedings of the National Academy of Sciences of the United States of America 97: 5440-5444. doi: 10.1073/pnas.97.10.5440
20. Koppel I, Timmusk T. 2013. Differential regulation of Bdnf expression in cortical neurons by class-selective histone deacetylase inhibitors. Neuropharmacology 75: 106-115. doi: 10.1016/j.neuropharm.2013.07.015
21. Leibowitz A, Klin Y, Gruenbaum BF, Gruenbaum SE, Kuts R, Dubilet M, Ohayon S, Boyko M, Sheiner E, Shapira Y, Zlotnik A. 2012. Effects of strong physical exercise on blood glutamate and its metabolite 2-ketoglutarate levels in healthy volunteers. Acta Neurobiologiae Experimentalis 72: 385-396.
22. Li Y-X, Xu Y, Ju D, Lester HA, Davidson N, Schuman EM. 1998. Expression of a dominant negative TrkB receptor, T1, reveals a requirement for presynaptic signaling in BDNF-induced synaptic potentiation in cultured hippocampal neurons. Proceedings of the National Academy of Sciences of the United States of America 95: 10884-10889. doi: 10.1073/pnas.95.18.10884
23. Li YX, Zhang Y, Lester HA, Schuman EM, Davidson N. 1998. Enhancement of neurotransmitter release induced by brain-derived neurotrophic factor in cultured hippocampal neurons. Journal of Neuroscience 18: 10231-10240.
24. Lim S, Chesser AS, Grima JC, Rappold PM, Blum D, Przedborski S, Tieu K. 2011. D-b-hydroxybutyrate is protective in mouse models of Huntington’s disease. PloS One 6: e24620. doi: 10.1371/journal.pone.0024620
25. Lu B, Nagappan G, Guan X, Nathan PJ, Wren P. 2013. BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nature Reviews 14: 401-416. doi: 10.1038/nrn3505
26. Maalouf M, Rho JM, Mattson MP. 2009. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Research Reviews 59: 293-315. doi: 10.1016/j.brainresrev.2008.09.002
27. Marais L, Stein DJ, Daniels WM. 2009. Exercise increases BDNF levels in the striatum and decreases depressive-like behavior in chronically stressed rats. Metabolic Brain Disease 24: 587-597. doi: 10.1007/s11011-009-9157-2
28. Marlatt MW, Potter MC, Lucassen PJ, van Praag H, van Praag H. 2012. Running throughout middle-age improves memory function, hippocampal neurogenesis, and BDNF levels in female C57BL/6J mice. Developmental Neurobiology 72: 943-952. doi: 10.1002/dneu.22009
29. Martinowich K, Manji H, Lu B. 2007. New insights into BDNF function in depression and anxiety. Nature Neuroscience 10: 1089-1093. doi: 10.1038/nn1971
30. Mitchell GA, Kassovska-Bratinova S, Boukaftane Y, Robert MF, Wang SP, Ashmarina L, Lambert M, Lapierre P, Potier E. 1995. Medical aspects of ketone body metabolism. Clinical and Investigative Medicine. MéDecine Clinique Et Experimentale 18: 193-216.
31. Murakami S, Imbe H, Morikawa Y, Kubo C, Senba E. 2005. Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly. Neuroscience Research 53: 129-139. doi: 10.1016/j.neures.2005.06.008
32. Neeper SA, Gómez-Pinilla F, Choi J, Cotman C. 1995. Exercise and brain neurotrophins. Nature 373. doi: 10.1038/373109a0
33. Newman JC, Verdin E. 2014. b-hydroxybutyrate: much more than a metabolite. Diabetes Research and Clinical Practice 106: 173-181. doi: 10.1016/j.diabres.2014.08.009
34. Noakes T, Spedding M. 2012. Olympics: Run for your life. Nature 487: 295-296. doi: 10.1038/487295a
35. Park H, Poo MM. 2013. Neurotrophin regulation of neural circuit development and function. Nature Reviews. Neuroscience 14: 7-23. doi: 10.1038/nrn3379
36. Pruunsild P, Sepp M, Orav E, Koppel I, Timmusk T. 2011. Identification of cis-elements and transcription factors regulating neuronal activity-dependent transcription of human BDNF gene. Journal of Neuroscience 31: 3295-3308. doi: 10.1523/JNEUROSCI.4540-10.2011
37. Ralser M, Wamelink MM, Struys EA, Joppich C, Krobitsch S, Jakobs C, Lehrach H. 2008. A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growth. Proceedings of the National Academy of Sciences of the United States of America 105: 17807-17811. doi: 10.1073/pnas.0803090105
38. Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E, Secher NH, Pedersen BK, Pilegaard H. 2009. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Experimental Physiology 94: 1062-1069. doi: 10.1113/expphysiol.2009.048512
39. Ratan RR, Murphy TH, Baraban JM. 1994. Oxidative stress induces apoptosis in embryonic cortical neurons. Journal of Neurochemistry 62: 376-379. doi: 10.1046/j.1471-4159.1994.62010376.x
40. Robinson AM, Williamson DH. 1980. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiological Reviews 60: 143-187.
41. Russo-Neustadt AA, Beard RC, Huang YM, Cotman CW. 2000. Physical activity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus. Neuroscience 101: 305-312. doi: 10.1016/S0306-4522(00)00349-3
42. Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RV, de Cabo R, Ulrich S, Akassoglou K, Verdin E. 2013. Suppression of oxidative stress by b-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339: 211-214. doi: 10.1126/science.1227166
43. Tabuchi A, Sakaya H, Kisukeda T, Fushiki H, Tsuda M. 2002. Involvement of an upstream stimulatory factor as well as cAMP-responsive element-binding protein in the activation of brain-derived neurotrophic factor gene promoter I. The Journal of Biological Chemistry 277: 35920-35931. doi: 10.1074/jbc.M204784200
44. Takei N, Numakawa T, Kozaki S, Sakai N, Endo Y, Takahashi M, Hatanaka H. 1998. Brain-derived neurotrophic factor induces rapid and transient release of glutamate through the non-exocytotic pathway from cortical neurons. The Journal of Biological Chemistry 273: 27620-27624. doi: 10.1074/jbc.273.42.27620
45. Takimoto M, Hamada T. 2014. Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins. Journal of Applied Physiology 116: 1238-1250. doi: 10.1152/japplphysiol.01288.2013
46. 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. The Journal of Clinical Investigation 112: 892-901. doi: 10.1172/JCI200318797
47. Vaynman S, Ying Z, Gomez-Pinilla F. 2004. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. The European Journal of Neuroscience 20: 2580-2590. doi: 10.1111/j.1460-9568.2004.03720.x
48. Vaynman SS, Ying Z, Yin D, Gomez-Pinilla F. 2006. Exercise differentially regulates synaptic proteins associated to the function of BDNF. Brain Research 1070: 124-130. doi: 10.1016/j.brainres.2005.11.062
49. Wagner FF, Lundh M, Kaya T, McCarren P, Zhang YL, Chattopadhyay S, Gale JP, Galbo T, Fisher SL, Meier BC, Vetere A, Richardson S, Morgan NG, Christensen DP, Gilbert TJ, Hooker JM, Leroy M, Walpita D, Mandrup-Poulsen T, Wagner BK, et al. 2016. An Isochemogenic Set of Inhibitors To Define the Therapeutic Potential of Histone Deacetylases in b-Cell Protection. ACS Chemical Biology 11: 363-437. doi: 10.1021/acschembio.5b00640
50. Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, Lin JD, Greenberg ME, Spiegelman BM, Spiegelman BM. 2013. Exercise induces hippocampal BDNF through a PGC-1a/FNDC5 pathway. Cell Metabolism 18: 649-659. doi: 10.1016/j.cmet.2013.09.008
51. Yano H, Ninan I, Zhang H, Milner TA, Arancio O, Chao MV. 2006. BDNF-mediated neurotransmission relies upon a myosin VI motor complex. Neuroscience 9: 1009-1018. doi: 10.1038/nn1730
52. Yao J, Chen S, Mao Z, Cadenas E, Brinton RD. 2011. 2-Deoxy-D-glucose treatment induces ketogenesis, sustains mitochondrial function, and reduces pathology in female mouse model of Alzheimer’s disease. PloS One 6: e21788. doi: 10.1371/journal.pone.0021788
53. Zuccato C, Cattaneo E. 2009. Brain-derived neurotrophic factor in neurodegenerative diseases. Nature Reviews. Neurology 5: 311-322. doi: 10.1038/nrneurol.2009.54