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The Journal of Neuroscience, July 30, 2003, 23(17):6690-6694
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BRIEF COMMUNICATION
Brain-Derived Neurotrophic Factor val66met Polymorphism Affects Human Memory-Related Hippocampal Activity and Predicts Memory Performance
Ahmad R. Hariri,
Terry E. Goldberg, *
Venkata S. Mattay, *
Bhaskar S. Kolachana,
Joseph H. Callicott,
Michael F. Egan, and
Daniel R. Weinberger
Clinical Brain Disorders Branch, Intramural Research Program, National
Institute of Mental Health, National Institutes of Health, United States
Department of Health and Human Services, Bethesda, Maryland 20892
BDNF plays a critical role in activity-dependent neuroplasticity underlying
learning and memory in the hippocampus. A frequent single nucleotide
polymorphism in the targeting region of the human BDNF gene
(val66met) has been associated with abnormal intracellular
trafficking and regulated secretion of BDNF in cultured hippocampal neurons
transfected with the met allele. In addition, the met allele has been
associated with abnormal hippocampal neuronal function as well as impaired
episodic memory in human subjects, but a direct effect of BDNF alleles on
hippocampal processing of memory has not been demonstrated. We studied the
relationship of the BDNF val66met genotype and hippocampal activity
during episodic memory processing using blood oxygenation level-dependent
functional magnetic resonance imaging and a declarative memory task in healthy
individuals. Met carriers exhibited relatively diminished hippocampal
engagement in comparison with val homozygotes during both encoding and
retrieval processes. Remarkably, the interaction between the BDNF
val66met genotype and the hippocampal response during encoding
accounted for 25% of the total variation in recognition memory performance.
These data implicate a specific genetic mechanism for substantial normal
variation in human declarative memory and suggest that the basic effects of
BDNF signaling on hippocampal function in experimental animals are important
in humans.
Key words: BDNF; hippocampus; human memory; gene; polymorphism; BOLD fMRI
Received Apr. 21, 2003;
revised May. 28, 2003;
accepted May. 29, 2003.
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