Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance
Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance
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DOI：
10.1523/jneurosci.23-17-06690.2003
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发表时间：
2003-07-30
影响因子：
5.3
通讯作者：
Weinberger, DR
中科院分区：
文献类型：
--
作者：
Hariri, AR;Goldberg, TE;Weinberger, DR
脑源性神经营养因子（BDNF）在海马的学习和记忆活动依赖性神经可塑性中起着关键作用。在人BDNF基因的靶向区域（瓦尔（66）met）中频繁的单核苷酸多态性与用met等位基因转染的培养的海马神经元中BDNF的异常细胞内运输和调节分泌相关。此外，在人类受试者中，met等位基因与海马神经元功能异常以及情节记忆受损相关，但BDNF等位基因对海马记忆加工的直接影响尚未得到证实。我们采用血氧水平依赖性功能磁共振成像和陈述性记忆任务研究了健康个体在情景记忆过程中BDNF瓦尔（66）met基因型与海马活动的关系。与瓦尔纯合子相比，Met携带者在编码和检索过程中都表现出相对减少的海马参与。值得注意的是，BDNF瓦尔（66）met基因型和编码过程中海马反应之间的相互作用占识别记忆表现总变异的25%。这些数据暗示了人类陈述性记忆中大量正常变异的特定遗传机制，并表明BDNF信号对实验动物海马功能的基本影响在人类中很重要。
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 (val (66)met) 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 val (66)met 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 val (66)met 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.