BDNF val66met Genotype and Age: Impact on Biomarkers and Exercise-based Treatment

描述(由申请人提供)：我们相信，这项研究通过提供关于基因(在这种情况下，包括Val66Met和来自另一种生长因子NGF的基因)对脑组织转录谱、脑结构、神经认知和运动治疗反应的影响的重要数据，充分揭示了我们对老龄化人类受试者行为变化的神经机制的理解。这一描述不仅是机械性的，而且将是完全翻译的，因为它始于1.通过对人类尸检样本的微阵列分析确定的对bdnf基因在大约48000个皮质转录本中的表达模式的分子理解；2.在结构核磁共振和神经认知中检测年龄x bdnf基因对神经解剖体积的影响，重点是情景记忆和内侧颞叶结构和影响调节；并包括3.一项概念验证随机试验，考察体育锻炼(旨在增加bdnf表达)和bdnf基因对认知终点的影响。如果这些研究中的预测是正确的，我们相信我们将有实用的、个性化的治疗方法来改善老年人的记忆

DESCRIPTION (provided by applicant): We believe that this study fully informs our understanding of neural mechanisms of behavioral change in aging human subjects by providing important data on the impact of genotype (in this case BDNF genotypes, including val66met and genotypes from another growth factor, NGF) on aging on transcriptional profiles in brain tissue, brain structure, neurocognition, and response to an exercise based treatment. This account will not only be mechanistic, but it will be fully translational in that it begins with 1. a molecular understanding of BDNF genotype modulate expression patterns in approximately 48000 cortical transcripts as determined by microarray profiling of human post mortem samples; 2. examines the impact of age x BDNF genotypes on neuroanatomic volumes in structural MRI and neurocognition with an emphasis on episodic memory and medial temporal lobe structures and affect regulation; and includes 3. a proof of concept randomized trial examining the impact of physical exercise (designed to increase BDNF expression) and BDNF genotypes on cognitive endpoints. If the predictions in these studies are correct, we believe that we will have practical, personalized treatments to improve memory in older populations