Hariri Ahmad R, Goldberg Terry E, Mattay Venkata S, Kolachana Bhaskar S, Callicott Joseph H, Egan Michael F, Weinberger Daniel R
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 20892-1384, USA.
J Neurosci. 2003 Jul 30;23(17):6690-4. doi: 10.1523/JNEUROSCI.23-17-06690.2003.
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.
脑源性神经营养因子（BDNF）在海马体中学习和记忆所依赖的活动依赖性神经可塑性方面发挥着关键作用。人类BDNF基因靶向区域的一种常见单核苷酸多态性（val66met）与转染了met等位基因的培养海马神经元中BDNF的细胞内运输异常和分泌调节有关。此外，met等位基因还与人类受试者的海马神经元功能异常以及情景记忆受损有关，但BDNF等位基因对海马体记忆处理的直接影响尚未得到证实。我们使用血氧水平依赖性功能磁共振成像和健康个体的陈述性记忆任务，研究了情景记忆处理过程中BDNF val66met基因型与海马体活动之间的关系。在编码和检索过程中，与val纯合子相比，met携带者的海马参与度相对降低。值得注意的是，BDNF val66met基因型与编码过程中海马体反应之间的相互作用占识别记忆表现总变异的25%。这些数据揭示了人类陈述性记忆中大量正常变异的一种特定遗传机制，并表明BDNF信号在实验动物中海马体功能的基本作用在人类中也很重要。
