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BDNF Val66Met polymorphism interacts with sex to influence bimanual motor control in healthy humans.

ABSTRACT: Brain-derived neurotrophic factor (BDNF) plays a critical role in brain development. A common single nucleotide polymorphism in the gene encoding BDNF (rs6265, Val66Met) affects BDNF release and has been associated with altered learning and memory performance, and with structural changes in brain morphology and corpus callosum integrity. BDNF Val66Met has more recently been shown to influence motor learning and performance. Some of the BDNF effects seem to be modulated by an individual's sex, but currently the relationship between BDNF and sex in the motor domain remains elusive. Here, we investigate the relationship between BDNF Val66Met genotype and an individual's sex in the motor system. Seventy-six healthy, previously genotyped, individuals performed a task in which the participant drew lines at different angles of varying difficulty. Subjects controlled the horizontal and vertical movement of the line on a computer screen by rotating two cylinders. We used this bimanual motor control task to measure contributions from both current motor function and the pre-existing interhemispheric connectivity. We report that BDNF genotype interacts with sex to influence the motor performance of healthy participants in this bimanual motor control task. We further report that the BDNF genotype by sex interaction was present in the more difficult trials only, which is in line with earlier findings that genetic effects may become apparent only when a system is challenged. Our results emphasize the importance of taking sex into account when investigating the role of BDNF genotype in the motor system.

SUBMITTER: Smolders R

PROVIDER: S-EPMC3500459 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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BDNF Val66Met polymorphism interacts with sex to influence bimanual motor control in healthy humans.

Smolders Ruud R Rijpkema Mark M Franke Barbara B Fernández Guillén G

Brain and behavior 20120904 6

Brain-derived neurotrophic factor (BDNF) plays a critical role in brain development. A common single nucleotide polymorphism in the gene encoding BDNF (rs6265, Val66Met) affects BDNF release and has been associated with altered learning and memory performance, and with structural changes in brain morphology and corpus callosum integrity. BDNF Val66Met has more recently been shown to influence motor learning and performance. Some of the BDNF effects seem to be modulated by an individual's sex, bu ...[more]

PMID: 23170235

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Project description:The val(66)met polymorphism in brain-derived neurotrophic factor (BDNF) has been associated with poorer outcomes after stroke. The mechanism for this finding remains uncertain but might be related to the reduced motor system activation associated with this polymorphism in healthy people.The current study examined whether the presence of the BDNF val(66)met polymorphism is associated with reduced motor system activation after stroke.Forty-two patients with stroke who were enrolled in 1 of 2 studies of robot-assisted arm motor therapy participated in the study. All participants were tested for the BDNF val(66)met polymorphism followed by functional magnetic resonance imaging during affected hand movement.Participants averaged 12 months poststroke and had wide-ranging motor deficits (Fugl-Meyer scale scores=14-60). Brain activation in participants without the BDNF val(66)met polymorphism (n=26) spanned bilateral motor networks with a larger volume (total=334 cc) than that found in participants with this polymorphism (n=16) (97 cc). Regional analyses were consistent. Participants without this polymorphism showed larger ipsilesional primary sensorimotor cortex activation volume and magnitude compared with those in whom the polymorphism was present.The extent to which these findings generalize to other populations of people with stroke, such as those with stroke <7 days prior, remains uncertain.Functional magnetic resonance imaging during affected hand movement showed decreased brain activation among participants with the BDNF val(66)met polymorphism compared with those lacking this polymorphism, especially in the ipsilesional primary sensorimotor cortex contralateral to movement. These results echo findings in healthy people and suggest that genetic factors affecting the normal brain continue to be operative after stroke. The findings suggest a potential imaging-based endophenotype for the BDNF val(66)met polymorphism's effect on the motor system that may be useful in a clinical trial setting.

Dataset Information

BDNF Val66Met polymorphism interacts with sex to influence bimanual motor control in healthy humans.

Publications

BDNF Val66Met polymorphism interacts with sex to influence bimanual motor control in healthy humans.

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