Effect of the interaction between BDNF Val66Met polymorphism and daily physical activity on mean diffusivity

  • Hikaru TakeuchiEmail author
  • Hiroaki Tomita
  • Yasuyuki Taki
  • Yoshie Kikuchi
  • Chiaki Ono
  • Zhiqian Yu
  • Atsushi Sekiguchi
  • Rui Nouchi
  • Yuka Kotozaki
  • Seishu Nakagawa
  • Carlos Makoto Miyauchi
  • Kunio Iizuka
  • Ryoichi Yokoyama
  • Takamitsu Shinada
  • Yuki Yamamoto
  • Sugiko Hanawa
  • Tsuyoshi Araki
  • Keiko Kunitoki
  • Yuko Sassa
  • Ryuta Kawashima


Numerous studies have reported that the Met allele of the brain-derived neurotrophic factor (BDNF) gene polymorphism reduces neural plasticity. A reduction in mean diffusivity (MD) in diffusion tensor imaging (DTI) characteristically reflects the neural plasticity that involves increased tissue components. In this study, we revealed that the number of Met-BDNF alleles was negatively associated with MD throughout the whole-brain gray and white matter areas of 743 subjects using DTI and whole-brain multiple regression analyses. Within the same sample, the region of interest analysis revealed that the number of Met-BDNF alleles significantly and positively correlated with the mean FA value in the body of the corpus callosum. In addition, we observed interaction effects between BDNF Val66Met polymorphism and daily physical activity levels on MD, but not FA, in significant clusters of the bilateral hemisphere (n = 577 subjects). Post-hoc multiple regression analyses revealed that after correcting for confounding variables, there was a significant negative correlation between the physical activity level and mean MD of the whole brain in the Val/Val group [standardized partial regression coefficient (β) = −0.196, P = 0.005, t = −2.825], but not in the Val/Met (β = 0.050, P = 0.412, t = 0.822) and Met/Met groups (β = 0.092, P = 0.382, t = 0.878). These results underscore the importance of the interaction between physical activity and the BDNF Val66Met polymorphism, which affects the plasticity of neural mechanisms.


BDNF Polymorphism Neural plasticity Mean diffusivity Diffusion tensor imaging Fractional anisotropy Physical activity 



We thank Yuki Yamada for operating the MRI scanner, Mutsumi Oohashi for performing the genotyping, all other assistants for helping with the experiments and the study, and the study participants and all our other colleagues at IDAC, Tohoku University for their support.

Author contributions

H.Takeuchi., H.Tomita., Y.T. and R.K. designed the study. H. Tomita supervised the study regarding polymorphisms. H.Tomita., Y.Kikuchi., C.O., and Z.Y. were involved in genotyping. H.Takeuchi., A.S., R.N., Y.Kotozaki., S.N., C.M.M., K.I., R.Y., T.S., Y.Y., S.H., T.A., K.K., and Y.S., collected the data. H.Takeuchi. analyzed the data and prepared the manuscript.


This study was supported by JST/RISTEX, JST/CREST, a Grant-in-Aid for Young Scientists (B) (KAKENHI 23700306) and a Grant-in-Aid for Young Scientists (A) (KAKENHI 25700012) from the Ministry of Education, Culture, Sports, Science, and Technology.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

Ethical approval

This study was approved by the Ethics Committee of Tohoku University. All experiments were performed in accordance with declaration of Helsinki.

Informed consent

Written informed consent was obtained from each participant in accordance with the Declaration of Helsinki (1991).

Supplementary material

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Authors and Affiliations

  • Hikaru Takeuchi
    • 1
    Email author
  • Hiroaki Tomita
    • 2
  • Yasuyuki Taki
    • 1
    • 3
    • 4
  • Yoshie Kikuchi
    • 2
  • Chiaki Ono
    • 2
  • Zhiqian Yu
    • 2
  • Atsushi Sekiguchi
    • 5
  • Rui Nouchi
    • 6
  • Yuka Kotozaki
    • 7
  • Seishu Nakagawa
    • 8
  • Carlos Makoto Miyauchi
    • 9
  • Kunio Iizuka
    • 8
    • 10
  • Ryoichi Yokoyama
    • 8
    • 11
  • Takamitsu Shinada
    • 8
  • Yuki Yamamoto
    • 8
  • Sugiko Hanawa
    • 8
  • Tsuyoshi Araki
    • 7
  • Keiko Kunitoki
    • 12
  • Yuko Sassa
    • 1
  • Ryuta Kawashima
    • 1
    • 7
    • 8
  1. 1.Division of Developmental Cognitive Neuroscience, Institute of Development, Aging and CancerTohoku UniversitySendaiJapan
  2. 2.Department of Disaster Psychiatry, International Research Institute of Disaster ScienceTohoku UniversitySendaiJapan
  3. 3.Division of Medical Neuroimage Analysis, Department of Community Medical Supports, Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
  4. 4.Department of Nuclear Medicine and Radiology, Institute of Development, Aging and CancerTohoku UniversitySendaiJapan
  5. 5.Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and PsychiatryTokyoJapan
  6. 6.Human and Social Response Research Division, International Research Institute of Disaster ScienceTohoku UniversitySendaiJapan
  7. 7.Smart Ageing International Research Center, Institute of Development, Aging and CancerTohoku UniversitySendaiJapan
  8. 8.Department of Functional Brain Imaging, Institute of Development, Aging and CancerTohoku UniversitySendaiJapan
  9. 9.Graduate School of Arts and Sciences, Department of General Systems StudiesThe University of TokyoTokyoJapan
  10. 10.Department of PsychiatryTohoku University Graduate School of MedicineSendaiJapan
  11. 11.Japan Society for the Promotion of ScienceTokyoJapan
  12. 12.Faculty of MedicineTohoku UniversitySendaiJapan

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