Abstract
Brain-derived neurotrophic factor (BDNF) modulates the pruning of synaptically silent axonal arbors. The Met allele of the BDNF gene is associated with a reduction in the neurotrophin's activity-dependent release. We used diffusion-weighted imaging to construct structural brain networks for 36 healthy subjects with known BDNF genotypes. Through permutation testing we discovered clear differences in connection strength between subjects carrying the Met allele and those homozygotic for the Val allele. We trained a Gaussian process classifier capable of identifying the subjects' allelic group with 86% accuracy and high predictive value. In Met carriers structural connectivity was greatly increased throughout the forebrain, particularly in connections corresponding to the anterior and superior corona radiata as well as corticothalamic and corticospinal projections from the sensorimotor, premotor, and prefrontal portions of the internal capsule. Interhemispheric connectivity was also increased via the corpus callosum and anterior commissure, and extremely high connectivity values were found between inferior medial frontal polar regions via the anterior forceps. We propose that the decreased availability of BDNF leads to deficits in axonal maintenance in carriers of the Met allele, and that this produces mesoscale changes in white matter architecture.
Highlights
Secretion of brain-derived neurotrophic factor is essential for synaptic plasticity in the central nervous system during neurodevelopment [1], as well as in mature brains, in which it promotes long-term potentiation and the formation of long-term memory [2,3]
Using high-resolution connectome mapping, we observe significant differences in structural brain connectivity between samples of normal young healthy human volunteers recruited based on the Met allele of the Brain-derived neurotrophic factor (BDNF) gene
These differences appear to involve specific fiber tracts; widespread, they do not modify connectome parameters computed over the whole brain. They appear specific to this allele; no such difference could be found for the polymorphism in the adenosine deaminase gene, or even for gender
Summary
Secretion of brain-derived neurotrophic factor is essential for synaptic plasticity in the central nervous system during neurodevelopment [1], as well as in mature brains, in which it promotes long-term potentiation and the formation of long-term memory [2,3]. A common human non-synonymous singlenucleotide polymorphism in the BDNF gene (Val66Met, rs6265) decreases activity-dependent BDNF release in neurons transfected with the human A allele (Met-BDNF) [4]. It is associated with variation in human memory [5,6], and with several neurological and psychiatric disorders [7]. We reasoned that the persistent differential activity-dependent BDNF release implied by this polymorphism should be associated with differences in adult brain structure. In this study we examine structural connectivity in the brains of normal human participants stratified according to BDNF genotypic group
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