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.
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