Advertisement

Journal of Molecular Neuroscience

, Volume 67, Issue 1, pp 82–88 | Cite as

The BDNF Val66Met Polymorphism Promotes Changes in the Neuronal Integrity and Alters the Time Perception

  • Victor MarinhoEmail author
  • Giovanny Rebouças Pinto
  • Rogério Figueiredo
  • Carla Ayres
  • Juliete Bandeira
  • Silmar Teixeira
Article
  • 59 Downloads

Abstract

Studies at the molecular level aim to integrate genetic and neurobiological data to provide an increasingly detailed understanding of phenotypes related to the synchronization ability and brain oscillations in time perception. Genetic variation as a modifying factor at cellular and neurochemical levels permeates several neurofunctional aspects in time-lapse duration concentrating from milliseconds to hours. Thus, the review presents the BDNF Val66Met polymorphism association in a dynamic frame of brain neurotrophic factor expression in the adaptation, integrity, and neuronal synchronism processes in the ability to estimate multisensory stimuli at different time intervals. Our study aims to understand the molecular aspects involved in a neurobiological domain pertinent to the time judgment, tracing a genetic profile of association with psychometric functions and behavioral performances related to timing stimuli.

Keywords

BDNF gene Time perception BDNF Val66Met Neurobiological aspects 

Notes

Authors’ Contributions

VM designed the study concept. GRP, CA, and ST read and finalized the manuscript. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Competing Interests

The authors declare that they have no competing interests.

Ethical Approval and Consent to Participate

Not applicable.

References

  1. Aghdaee SM, Battelli L, Assad JA (2014) Relative timing: from behaviour to neurons. Philos Trans R Soc B 369:20120472CrossRefGoogle Scholar
  2. Allman MJ, Teki S, Griffiths TD, Meck WH (2014) Properties of the internal clock: first-and second-order principles of subjective time. Annu Rev Psychol 65:743–771PubMedCrossRefGoogle Scholar
  3. Anastasia A, Deinhardt K, Chao MV, Will NE, Irmady K, Lee FS, Hempstead BL, Bracken C (2013) Val66Met polymorphism of BDNF alters prodomain structure to induce neuronal growth cone retraction. Nat Commun 4:2490PubMedPubMedCentralCrossRefGoogle Scholar
  4. Arcuri L, Viaro R, Bido S, Longo F, Calcagno M, Fernagut PO, Zaveri NT, Calò G, Bezard E, Morari M (2016) Genetic and pharmacological evidence that endogenous nociceptin/orphanin FQ contributes to dopamine cell loss in Parkinson’s disease. Neurobiol Dis 22(89):55–64CrossRefGoogle Scholar
  5. Balci F, Ludvig EA, Abner R, Zhuang X, Poon P, Brunner D (2010) Motivational effects on interval timing in dopamine transporter (DAT) knockdown mice. Brain Res 1325(14):89–99PubMedCrossRefGoogle Scholar
  6. Bartholomew AJ, Meck WH, Cirulli ET (2015) Analysis of genetic and non-genetic factors influencing timing and time perception. PLoS One 10(12):e0143873PubMedPubMedCentralCrossRefGoogle Scholar
  7. Block RA, Grondin S (2014) Timing and time perception: a selective review and commentary on recent reviews. Front Psychol 5:648PubMedPubMedCentralCrossRefGoogle Scholar
  8. Chang HA, Lu RB, Shy MJ, Chang CC, Lee MS, Huang SY (2009) Brain-derived neurotrophic factor Val66Met polymorphism: association with psychopathological symptoms of schizophrenia? J Neuropsychiatr Clin Neurosci 21:30–37CrossRefGoogle Scholar
  9. Cheeran B, Talelli P, Mori F, Koch G, Suppa A, Edwards M, Houlden H, Bhatia K, Greenwood R, Rothwell JC (2008) A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS. J Physiol 586(23):5717–5725PubMedPubMedCentralCrossRefGoogle Scholar
  10. Chen CC, Chen CJ, Wu D, Chi NF, Chen PC, Liao YP, Chiu HW, Hu CJ (2015) BDNF Val66Met polymorphism on functional MRI during n-back working memory tasks. Medicine (Baltimore) 94(42):e1586CrossRefGoogle Scholar
  11. Cirulli F, Berry A, Chiarotti F, Alleva E (2004) Intrahippocampal administration of BDNF in adult rats affects short-term behavioral plasticity in the Morris water maze and performance in the elevated plus-maze. Hippocampus 14:802e7CrossRefGoogle Scholar
  12. Cirulli ET, Kasperaviciūte D, Attix DK, Need AC, Ge D, Gibson G, Goldstein DB (2010) Common genetic variation and performance on standardized cognitive tests. Eur J Hum Genet 18(7):815–820PubMedPubMedCentralCrossRefGoogle Scholar
  13. Coull JT, Vidal F, Nazarian B, Macar F (2004) Functional anatomy of the attentional modulation of time estimation. Science 5:1506–1508CrossRefGoogle Scholar
  14. Coull JT, Cheng RK, Meck WH (2011) Neuroanatomical and neurochemical substrates of timing. Neuropsychopharmacology 36(1):3–25PubMedCrossRefGoogle Scholar
  15. Das D, Tan X, Bielak AA, Cherbuin N, Easteal S, Anstey KJ (2014) Cognitive ability, intraindividual variability, and common genetic variants of catechol-O-methyltransferase and brain-derived neurotrophic factor: a longitudinal study in a population-based sample of older adults. Psychol Aging 29(2):393–403PubMedCrossRefGoogle Scholar
  16. Droit-Volet S (2013) Time perception, emotions and mood disorders. J Physiol Paris 107:255–264PubMedCrossRefGoogle Scholar
  17. Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112(2):257–269PubMedCrossRefGoogle Scholar
  18. Fallgatter AJ, Herrmann MJ, Roemmler J, Ehlis AC, Wagener A, Heidrich A, Ortega G, Zeng Y, Lesch KP (2004) Allelic variation of serotonin transporter function modulates the brain electrical response for error processing. Neuropsychopharmacology 29(8):1506–1511PubMedCrossRefGoogle Scholar
  19. Fang H, Zhen YF, Liu XY, Xu G, Soares JC, Zhao J, Zhang XY (2016) Association of the BDNF Val66Met polymorphism with BMI in chronic schizophrenic patients and healthy controls. Int Clin Psychopharmacol 31(6):353–357PubMedCrossRefGoogle Scholar
  20. Finnerty GT, Shadlen MN, Jazayeri M, Nobre AC, Buonomano DV (2015) Time in cortical circuits. J Neurosci 35(41):13912–13916PubMedPubMedCentralCrossRefGoogle Scholar
  21. Fontes R, Ribeiro J, Gupta DS, Machado D, Lopes-Júnior F, Magalhães F, Bastos VH, Rocha K, Marinho V, Lima G, Velasques B, Ribeiro P, Orsini M, Pessoa B, Leite MA, Teixeira S (2016) Time perception mechanisms at central nervous system. Neurol Int 8(1):5939PubMedPubMedCentralCrossRefGoogle Scholar
  22. Green AE, Munafò MR, DeYoung CG, Fossella JA, Fan J, Gray JR (2008) Using genetic data in cognitive neuroscience: from growing pains to genuine insights. Nat Rev Neurosci 9(9):710–720PubMedCrossRefGoogle Scholar
  23. Gupta DS (2014) Processing of sub- and supra-second intervals in the primate brain results from the calibration of neuronal oscillators via sensory, motor, and feedback processes. Front Psychol 5:816PubMedPubMedCentralCrossRefGoogle Scholar
  24. Gupta DS, Chen L (2016) Brain oscillations in perception, timing and action. Curr Opin Behav Sci 8:161–166CrossRefGoogle Scholar
  25. Gupta D, Merchant H (2017). Understanding the role of the time dimension in the brain information processing. Front Psychol 8Google Scholar
  26. Hariri AR, Goldberg TE, Mattay VS, Kolachana BS, Callicott JH, Egan MF, Weinberger DR (2003) Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. J Neurosci 23:6690–6694PubMedCrossRefGoogle Scholar
  27. Herai T, Mogi K (2014) Perception of temporal duration affected by automatic and controlled movements. Conscious Cogn 29:23–35PubMedCrossRefGoogle Scholar
  28. Hwang JP, Tsai SJ, Hong CJ, Yang CH, Lirng JF, Yang YM (2006) The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression. Neurobiol Aging 27:1834–1837PubMedCrossRefGoogle Scholar
  29. Ivry RB, Spencer RM (2004) The neural representation of time. Curr Opin Neurobiol 14(2):225–232PubMedCrossRefGoogle Scholar
  30. Joliot M, Ribary U, Llinas R (1994) Human oscillatory brain activity near 40 Hz coexists with cognitive temporal binding. Proc Natl Acad Sci U S A 91:11748–11751PubMedPubMedCentralCrossRefGoogle Scholar
  31. Jones CRG, Jahanshahi M (2011) Dopamine modulates striato-frontal functioning during temporal processing. Front Integr Neurosci 5:70PubMedPubMedCentralGoogle Scholar
  32. Jung T, Vogiatzian F, Har-Shemesh O, Fitzsimons C, Quax R (2014) Applying information theory to neuronal networks: from theory to experiments. Entropy 16:5721–5737CrossRefGoogle Scholar
  33. Kailainathan S, Piers TM, Yi JH, Choi S, Fahey MS, Borger E, Gunn-Moore FJ, O’Neill L, Lever M, Whitcomb DJ, Cho K, Allen SJ (2016) Activation of a synapse weakening pathway by human Val66 but not Met66 pro-brain-derived neurotrophic factor (proBDNF). Pharmacol Res 104:97–107PubMedPubMedCentralCrossRefGoogle Scholar
  34. Lake JI, Meck WH (2013) Differential effects of amphetamine and haloperidol on temporal reproduction: dopaminergic regulation of attention and clock speed. Neuropsychologia 51(2):284–292PubMedCrossRefGoogle Scholar
  35. Lamb YN, McKay NS, Thompson CS, Hamm JP, Waldie KE, Kirk IJ (2015) Brain-derived neurotrophic factor Val66Met polymorphism, human memory, and synaptic neuroplasticity. Wiley Interdiscip Rev Cogn Sci 6(2):97–108PubMedCrossRefGoogle Scholar
  36. Lee SY, Wang TY, Chen SL, Chang YH, Chen PS, Huang SY, Tzeng NS, Wang LJ, Lee IH, Chen KC, Yang YK, Yang YH, Lu RB, Chen CS (2016) The correlation between plasma brain-derived neurotrophic factor and cognitive function in bipolar disorder is modulated by the BDNF Val66Met polymorphism. Sci Rep 6:37950PubMedPubMedCentralCrossRefGoogle Scholar
  37. Marinho V, Oliveira T, Bandeira J, Pinto GR, Gomes A, Lima V, Magalhães F, Rocha K, Ayres C, Carvalho V, Velasques B, Ribeiro P, Orsini M, Bastos VH, Gupta D, Teixeira S (2018a) Genetic influence alters the brain synchronism in perception and timing. J Biomed Sci 25(1):61.  https://doi.org/10.1186/s12929-018-0463-z PubMedPubMedCentralCrossRefGoogle Scholar
  38. Marinho V, Oliveira T, Rocha K, Ribeiro J, Magalhães F, Bento T, Pinto GR, Velasques B, Ribeiro P, Di Giorgio L, Orsini M, Gupta DS, Bittencourt J, Bastos VH, Teixeira S (2018b) The dopaminergic system dynamic in the time perception: a review of the evidence. Int J Neurosci 128(3):262–282PubMedCrossRefGoogle Scholar
  39. Matthews WJ, Meck WH (2014) Time perception: the bad news and the good. Wiley Interdiscip Rev Cogn Sci 5(4):429–446PubMedPubMedCentralCrossRefGoogle Scholar
  40. Mauk MD, Buonomano DV (2004). The neural basis of temporal processing. Annu Rev Neurosci (27):307–340Google Scholar
  41. Merchant H, Harrington DL, Meck WH (2013) Neural basis of the perception and estimation of time. Annu Rev Neurosci 36:313–336PubMedCrossRefGoogle Scholar
  42. Merchant H, Grahn J, Trainor L, Rohrmeier M, Fitch WT (2015) Finding the beat: a neural perspective across humans and non-human primates. Philos Trans R Soc Lond Ser B Biol Sci 370:20140093CrossRefGoogle Scholar
  43. Mu JS, Li WP, Yao ZB, Zhou XF (1999) Deprivation of endogenous brain-derived neurotrophic factor results in impairment of spatial learning and memory in adult rats. Brain Res 835:259e65CrossRefGoogle Scholar
  44. Müller DJ, de Luca V, Sicard T, King N, Strauss J, Kennedy JL (2006) Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder: family-based association study. Br J Psychiatry 189:317–323PubMedCrossRefGoogle Scholar
  45. Ninan I (2014) Synaptic regulation of affective behaviors; role of BDNF. Neuropharmacology 76(Pt C):684–695PubMedCrossRefGoogle Scholar
  46. Oprisan SA, Buhusi CV (2013) Why noise is useful in functional and neural mechanisms of interval timing? BMC Neurosci 14:84 2013PubMedPubMedCentralCrossRefGoogle Scholar
  47. Piepmeier AT, Etnier JL (2015) Brain-derived neurotrophic factor (BDNF) as a potential mechanism of the effects of acute exercise on cognitive performance. J Sport Health Sci 4:4–23CrossRefGoogle Scholar
  48. Pouille F, Scanziani M (2001) Enforcement of temporal fidelity in pyramidal cells by somatic feed-forward inhibition. Science 293(5532):1159–1163PubMedCrossRefGoogle Scholar
  49. Rosa A, Cuesta MJ, Fatjó-Vilas M, Peralta V, Zarzuela A, Fañanás L (2006) The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with risk for psychosis: evidence from a family-based association study. Am J Med Genet B Neuropsychiatr Genet 141B:135–138PubMedCrossRefGoogle Scholar
  50. Saghazadeh A, Esfahani SA, Rezaei N (2016) Genetic polymorphisms and the adequacy of brain stimulation: state of the art. Expert Rev Neurother 16(9):1043–1054PubMedCrossRefGoogle Scholar
  51. Teixeira S, Machado S, Paes F, Velasques B, Silva JG, Sanfim AL, Minc D, Anghinah R, Menegaldo LL, Salama M, Cagy M, Nardi AE, Pöppel E, Bao Y, Szelag E, Ribeiro P, Arias-Carrión O (2013) Time perception distortion in neuropsychiatric and neurological disorders. CNS Neurol Disord Drug Targets 12:567–582PubMedCrossRefGoogle Scholar
  52. Teixeira S, Magalhães F, Marinho V, Velasques B, Ribeiro P (2016) Proposal for using time estimation training for the treatment of Parkinson’s disease. Med Hypotheses 95:58–61PubMedCrossRefGoogle Scholar
  53. Van Rijn H, Gu BM, Meck WH (2014) Dedicated clock/timing-circuit theories of time perception and timed performance. Adv Exp Med Biol 829:75–99PubMedCrossRefGoogle Scholar
  54. Wang L, Fontanini A, Maffei A (2012) Experience-dependent switch in sign and mechanisms for plasticity in layer 4 of primary visual cortex. J Neurosci 32:10562–10573PubMedPubMedCentralCrossRefGoogle Scholar
  55. Wheeler AL, Felsky D, Viviano JD, Stojanovski S, Ameis SH, Szatmari P, Lerch JP, Chakravarty MM, Voineskos AN (2017) BDNF-dependent effects on amygdala-cortical circuitry and depression risk in children and youth. Cereb Cortex 6:1–11Google Scholar
  56. Wiegand A, Nieratschker V, Plewnia C (2016) Genetic modulation of transcranial direct current stimulation effects on cognition. Front Hum Neurosci 10:651PubMedPubMedCentralCrossRefGoogle Scholar
  57. Wiener M, Turkeltaub P, Coslett HB (2010) The image of time: a voxel-wise meta-analysis. NeuroImage 49:1728–1740PubMedCrossRefGoogle Scholar
  58. Wiener M, Lohoff FW, Coslett HB (2011) Double dissociation of dopamine genes and timing in humans. J Cogn Neurosci 23:2811–2821PubMedCrossRefGoogle Scholar
  59. Wiłkość M, Szałkowska A, Skibińska M, Zając-Lamparska L, Maciukiewicz M, Araszkiewicz A (2016) BDNF gene polymorphisms and haplotypes in relation to cognitive performance in Polish healthy subjects. Acta Neurobiol Exp (Wars) 76(1):43–52Google Scholar
  60. Yger P, Gilson M (2015). Models of metaplasticity: a review of concepts. Front Comput Neurosci. (9):138Google Scholar
  61. Zhang XY, Chen d C, Tan YL, Tan S, Luo X, Zuo L, Soares JC (2016) BDNF polymorphisms are associated with cognitive performance in schizophrenia patients versus healthy controls. J Clin Psychiatry 77(8):e1011–e1018Google Scholar
  62. Zilles D, Meyer J, Schneider-Axmann T, Ekawardhani S, Gruber E, Falkai P, Gruber O (2012) Genetic polymorphisms of 5-HTT and DAT but not COMT differentially affect verbal and visuospatial working memory functioning. Eur Arch Psychiatry Clin Neurosci 262(8):667–676PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Neuro-innovation Technology & Brain Mapping LaboratoryFederal University of PiauíParnaíbaBrazil
  2. 2.Genetics and Molecular Biology LaboratoryFederal University of PiauíParnaíbaBrazil
  3. 3.The Northeast Biotechnology Network (RENORBIO)Federal University of PiauíTeresinaBrazil
  4. 4.Teresina Unified Education Center - CEUTTeresinaBrazil

Personalised recommendations