Abstract
The val66met polymorphism in the brain-derived neurotrophic factor (BDNF) gene impacts activity-dependent secretion of BDNF and modifies short-term cortical plasticity. The current study examined whether sustained training overcomes polymorphism effects on short-term plasticity and also examined polymorphism effects on long-term plasticity. Twenty-four subjects completed a 12-day protocol of daily training on a marble navigation task that required intense use of the first dorsal interosseus (FDI) muscle. In parallel, transcranial magnetic stimulation (TMS) mapping was used to assess serial measures of short-term cortical motor map plasticity, plus long-term cortical motor map plasticity, of the cortical FDI map. On Day 1, subjects with the polymorphism did not show significant short-term cortical motor map plasticity over 30 min of FDI activity, but subjects without the polymorphism did. After 5 days of intense training, a genotype-based difference in short-term cortical motor map plasticity was no longer found, as both groups showed short-term plasticity across the 30 min of FDI activity. Also, across 12 days of training, map area decreased significantly, in a manner that did not vary in relation to genotype. Training of sufficient intensity and duration overcomes effects that the val66met polymorphism has on short-term cortical motor map plasticity. The polymorphism-related differences seen with short-term plasticity are not found with long-term cortical motor map plasticity.
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References
Bath KG, Lee FS (2006) Variant BDNF (Val66Met) impact on brain structure and function. Cogn Affect Behav Neurosci 6:79–85
Berchtold NC, Castello N, Cotman CW (2010) Exercise and time-dependent benefits to learning and memory. Neuroscience 167:588–597
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 586:5717–5725
Chen J, Zhang C, Jiang H, Li Y, Zhang L, Robin A, Katakowski M, Lu M, Chopp M (2005) Atorvastatin induction of VEGF and BDNF promotes brain plasticity after stroke in mice. J Cereb Blood Flow Metab 25:281–290
Costa RM, Cohen D, Nicolelis MA (2004) Differential corticostriatal plasticity during fast and slow motor skill learning in mice. Curr Biol 14:1124–1134
Cramer SC, Sampat A, Haske-Palomino M, Nguyen S, Procaccio V, Hermanowicz N (2010) Increased prevalence of val(66)met BDNF genotype among subjects with cervical dystonia. Neurosci Lett 468:42–45
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 112:257–269
Floyer-Lea A, Matthews PM (2005) Distinguishable brain activation networks for short- and long-term motor skill learning. J Neurophysiol 94:512–518
Fritsch B, Reis J, Martinowich K, Schambra HM, Ji Y, Cohen LG, Lu B (2010) Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron 66:198–204
Gines S, Bosch M, Marco S, Gavalda N, Diaz-Hernandez M, Lucas JJ, Canals JM, Alberch J (2006) Reduced expression of the TrkB receptor in Huntington’s disease mouse models and in human brain. Eur J Neurosci 23:649–658
Gomez-Pinilla F, Ying Z, Roy RR, Molteni R, Edgerton VR (2002) Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol 88:2187–2195
Hashimoto K (2007) BDNF variant linked to anxiety-related behaviors. Bioessays 29:116–119
Ho BC, Milev P, O’Leary DS, Librant A, Andreasen NC, Wassink TH (2006) Cognitive and magnetic resonance imaging brain morphometric correlates of brain-derived neurotrophic factor Val66Met gene polymorphism in patients with schizophrenia and healthy volunteers. Arch Gen Psychiatry 63:731–740
Ji Y, Lu Y, Yang F, Shen W, Tang TT, Feng L, Duan S, Lu B (2010) Acute and gradual increases in BDNF concentration elicit distinct signaling and functions in neurons. Nat Neurosci 13:302–309
Kang H, Schuman EM (1995) Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. Science 267:1658–1662
Karni A, Meyer G, Jezzard P, Adams MM, Turner R, Ungerleider LG (1995) Functional MRI evidence for adult motor cortex plasticity during motor skill learning. Nature 377:155–158
Kleim JA, Cooper NR, VandenBerg PM (2002) Exercise induces angiogenesis but does not alter movement representations within rat motor cortex. Brain Res 934:1–6
Kleim JA, Hogg TM, VandenBerg PM, Cooper NR, Bruneau R, Remple M (2004) Cortical synaptogenesis and motor map reorganization occur during late, but not early, phase of motor skill learning. J Neurosci 24:628–633
Kleim JA, Chan S, Pringle E, Schallert K, Procaccio V, Jimenez R, Cramer SC (2006) BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nat Neurosci 9:735–737
Kleim JA, Kleim ED, Cramer SC (2007) Systematic assessment of training-induced changes in corticospinal output to hand using frameless stereotaxic transcranial magnetic stimulation. Nat Protoc 2:1675–1684
Li J, Ding YH, Rafols JA, Lai Q, McAllister JP 2nd, Ding Y (2005) Increased astrocyte proliferation in rats after running exercise. Neurosci Lett 386:160–164
McHughen SA, Rodriguez PF, Kleim JA, Kleim ED, Crespo LM, Procaccio V, Cramer SC (2010) BDNF val66met polymorphism influences motor system function in the human brain. Cereb Cortex 20:1254–1262
Nagappan G, Lu B (2005) Activity-dependent modulation of the BDNF receptor TrkB: mechanisms and implications. Trends Neurosci 28:464–471
Neeper SA, Gomez-Pinilla F, Choi J, Cotman C (1995) Exercise and brain neurotrophins. Nature 373:109
Pascual-Leone A, Nguyet D, Cohen L, Brasil-Neto J, Cammarota A, Hallett M (1995) Modulation of muscle responses evoked by transcranial magnetic stimulation during the acquisition of new fine motor skills. J Neurophysiol 74:1037–1045
Pezawas L, Verchinski BA, Mattay VS, Callicott JH, Kolachana BS, Straub RE, Egan MF, Meyer-Lindenberg A, Weinberger DR (2004) The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. J Neurosci 24:10099–10102
Pezet S, Malcangio M, McMahon SB (2002) BDNF: a neuromodulator in nociceptive pathways? Brain Res Brain Res Rev 40:240–249
Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso G, Cracco RQ, Dimitrijevic MR, Hallett M, Katayama Y, Lucking CH et al (1994) Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalogr Clin Neurophysiol 91:79–92
Rybakowski JK (2008) BDNF gene: functional Val66Met polymorphism in mood disorders and schizophrenia. Pharmacogenomics 9:1589–1593
Shimizu E, Hashimoto K, Iyo M (2004) Ethnic difference of the BDNF 196G/A (val66met) polymorphism frequencies: the possibility to explain ethnic mental traits. Am J Med Genet B Neuropsychiatr Genet 126:122–123
Siironen J, Juvela S, Kanarek K, Vilkki J, Hernesniemi J, Lappalainen J (2007) The Met allele of the BDNF Val66Met polymorphism predicts poor outcome among survivors of aneurysmal subarachnoid hemorrhage. Stroke 38:2858–2860
Simmons DA, Rex CS, Palmer L, Pandyarajan V, Fedulov V, Gall CM, Lynch G (2009) Up-regulating BDNF with an ampakine rescues synaptic plasticity and memory in Huntington’s disease knockin mice. Proc Natl Acad Sci U S A 106:4906–4911
Swain RA, Harris AB, Wiener EC, Dutka MV, Morris HD, Theien BE, Konda S, Engberg K, Lauterbur PC, Greenough WT (2003) Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat. Neuroscience 117:1037–1046
Wu D (2005) Neuroprotection in experimental stroke with targeted neurotrophins. Neurorx 2:120–128
Zuccato C, Cattaneo E (2009) Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 5:311–322
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This study was supported by grants from the National Institutes of Health: NS058755 and 5M011 RR-00827-29.
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McHughen, S.A., Pearson-Fuhrhop, K., Ngo, V.K. et al. Intense training overcomes effects of the val66met BDNF polymorphism on short-term plasticity. Exp Brain Res 213, 415–422 (2011). https://doi.org/10.1007/s00221-011-2791-z
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DOI: https://doi.org/10.1007/s00221-011-2791-z