Journal of Neural Transmission

, Volume 115, Issue 9, pp 1321–1325 | Cite as

Investigation of the functional brain-derived neurotrophic factor gene variant Val66MET in migraine

  • Martin Marziniak
  • Andrea Herzog
  • Rainald Mössner
  • Claudia Sommer
Basic Neurosciences, Genetics and Immunology - Original Article


Experimental studies and investigations of the cerebrospinal fluid in migraineurs have suggested an involvement of brain-derived neurotrophic factor (BDNF) in migraine pathophysiology. In a case–control study approach, the functional Val66MET polymorphism (rs6265) of the BDNF gene was investigated in 265 migraine patients and 153 controls. Genotype and allele frequencies did not differ between healthy subjects and migraineurs. A subgroup analysis for the occurrence of aura or clinical characteristics, including the number of attacks, did not reveal a positive association for the investigated polymorphism. Our data argue against a role of this well characterized BDNF gene variant as a risk factor in migraine.


Brain-derived neurotrophic factor Polymorphism Migraine Calcitonin-gene-related peptide 


  1. Angelucci F, Brene S, Mathe AA (2005) BDNF in schizophrenia, depression and corresponding animal models. Mol Psychiatry 10:345–352PubMedCrossRefGoogle Scholar
  2. Blandini F, Rinaldi L, Tassorelli C, Sances G, Motta M, Samuele A, Fancellu R, Nappi G, Leon A (2006) Peripheral levels of BDNF and NGF in primary headaches. Cephalalgia 26:136–142PubMedCrossRefGoogle Scholar
  3. Buldyrev I, Tanner NM, Hsieh H, Dodd EG, Nguyen LT, Balkowiec A (2006) Calcitonin gene-related peptide enhances release of native brain-derived neurotrophic factor from trigeminal ganglion neurons. J Neurochem 99:1338–1350PubMedCrossRefGoogle Scholar
  4. Chen ZY, Patel PD, Sant G, Meng CX, Teng KK, Hempstead BL, Lee FS (2004) Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci 24:4401–4411PubMedCrossRefGoogle Scholar
  5. 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 112:257–269PubMedCrossRefGoogle Scholar
  6. Gratacos M, Gonzalez JR, Mercader JM, de Cid R, Urretavizcaya M, Estivill X (2007) Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol Psychiatry 61:911–922PubMedCrossRefGoogle Scholar
  7. Hohoff C, Marziniak M, Lesch KP, Deckert J, Sommer C, Mossner R (2007) An adenosine A2A receptor gene haplotype is associated with migraine with aura. Cephalalgia 27:177–181PubMedCrossRefGoogle Scholar
  8. Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350:230–232PubMedCrossRefGoogle Scholar
  9. Kerr BJ, Bradbury EJ, Bennett DLH, Trivedi PM, Dassan P, French J, Shelton DB, McMahon SB, Thompson SWN (1999) Brain-derived neurotrophic factor modulates nociceptive sensory inputs and NMDA-evoked responses in the rat spinal cord. J Neurosci 19:5138–5148PubMedGoogle Scholar
  10. Lewin GR, Rueff A, Mendell LM (1994) Peripheral and central mechanisms of NGF-induced hyperalgesia. Eur J Neurosci 6:1903–1912PubMedCrossRefGoogle Scholar
  11. Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM, Yancopoulos GD (1990) Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science 247:1446–1451PubMedCrossRefGoogle Scholar
  12. Mamounas LA, Blue ME, Siuciak JA, Altar CA (1995) Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain. J Neurosci 15:7929–7939PubMedGoogle Scholar
  13. Marziniak M, Mössner R, Schmitt A, Lesch KP, Sommer C (2005) A functional serotonin transporter gene polymorphism is associated with migraine with aura. Neurology 64:157–159PubMedGoogle Scholar
  14. Marziniak M, Mössner R, Kienzler K, Riederer P, Lesch KP, Sommer C (2007) Functional polymorphisms of the 5-HT1A and 5-HT1B receptor are associated with clinical symptoms in migraineurs. J Neural Transm 114:1227–1232PubMedCrossRefGoogle Scholar
  15. Mössner R, Daniel S, Albert D, Heils A, Okladnova O, Schmitt A, Lesch KP (2000) Serotonin transporter function is modulated by brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF). Neurochem Int 36:197–202PubMedCrossRefGoogle Scholar
  16. Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier U, Pollentier S, Lesko LM (2004) BIBN 4096 BS clinical proof of concept study group calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 350:1104–1110PubMedCrossRefGoogle Scholar
  17. Pezet S, Malcangio M (2004) Brain-derived neurotrophic factor as a drug target for CNS disorders. Expert Opin Ther Targets 8:391–399PubMedCrossRefGoogle Scholar
  18. Pezet S, McMahon SB (2006) Neurotrophins: mediators and modulators of pain. Annu Rev Neurosci 29:507–538PubMedCrossRefGoogle Scholar
  19. Sarchielli P, Gallai V (2004) Nerve growth factor and chronic daily headache: a potential implication for therapy. Expert Rev Neurother 4:115–127PubMedCrossRefGoogle Scholar
  20. Sarchielli P, Alberti A, Gallai B, Coppoloa F, Baldi A, Floridi A, Gallai V (2002) Brain-derived neurotrophic factor in cerebrospinal fluid of patients with chronic daily headache: relationship with nerve growth factor and glutamate levels. J Headache Pain 3:129–135CrossRefGoogle Scholar
  21. Seidah NG, Benjannet S, Pareek S, Chretien M, Murphy RA (1996) Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases. FEBS Lett 379:247–250PubMedCrossRefGoogle Scholar
  22. Sen S, Nesse RM, Stoltenberg SF, Li S, Gleiberman L, Chakravarti A, Weder AB, Burmeister M (2003) A BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression. Neuropsychopharmacology 28:397–401PubMedCrossRefGoogle Scholar
  23. Small DL, Murray CL, Mealing GA, Poulter MO, Buchan AM, Morley P (1998) Brain derived neurotrophic factor induction of N-methyl-D-aspartate receptor subunit NR2A expression in cultured rat cortical neurons. Neurosci Lett 252:211–214PubMedCrossRefGoogle Scholar
  24. Suen PC, Wu K, Levine ES, Mount HT, Xu JL, Lin SY, Black IB (1997) Brain-derived neurotrophic factor rapidly enhances phosphorylation of the postsynaptic N-methyl-D-aspartate receptor subunit 1. Proc Natl Acad Sci USA 94:8191–8195PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Martin Marziniak
    • 1
    • 2
    • 3
  • Andrea Herzog
    • 4
  • Rainald Mössner
    • 4
    • 5
  • Claudia Sommer
    • 1
  1. 1.Department of NeurologyUniversity of WürzburgWürzburgGermany
  2. 2.Department of NeurologySaarland UniversityHomburg/SaarGermany
  3. 3.Department of NeurologyUniversity of MünsterMünsterGermany
  4. 4.Department of Psychiatry and PsychotherapyUniversity of WürzburgWürzburgGermany
  5. 5.Department of Psychiatry and PsychotherapyUniversity of BonnBonnGermany

Personalised recommendations