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

BDNF val66met 基因型和年龄：对生物标志物和运动治疗的影响

• 批准号: 8328894
• 负责人: Terry Goldberg
• 金额: $ 26.85万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8328894
• 关键词: 11p13; Accounting; Aerobic Exercise; Affect; Affective; Age; Aging; Alleles; Animals; BDNF gene; Behavior; Behavioral; Biological; Biological Markers; Brain; Brain-Derived Neurotrophic Factor; CREB1 gene; Cardiovascular system; Chromosomes; Cognition; Cognitive; Data; Docking; Emotional; Episodic memory; Exercise; Frequencies; Gene Expression Profiling; Genes; Genetic Polymorphism; Genetic Transcription; Genotype; Goals; Growth Factor; Homozygote; Human; Individual; Individual Differences; Magnetic Resonance Imaging; Measures; Medial; Memory; Mental Depression; Methionine; Molecular; Molecular Chaperones; N-Methyl-D-Aspartate Receptors; NR1 gene; Neuroanatomy; Neurocognition; Older Population; Pathway interactions; Pattern; Performance; Phase; Play; Property; Protein Biosynthesis; Proteins; Psyche structure; Regulation; Risk; Role; Sampling; Signal Transduction; Structure; Synaptic Receptors; Synaptic Transmission; Temporal Lobe; Testing; Tissues; Transcript; Valine; Variant; Vesicle; base; brain tissue; design; fitness; human subject; improved; in vivo; interest; memory process; neurochemistry; neuromechanism; postsynaptic; presynaptic; programs; randomized trial; receptor; response; trafficking; treatment program

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

描述（由申请人提供）：我们相信，这项研究通过提供关于基因型（在本例中为 BDNF 基因型，包括 val66met 和来自另一种生长因子 NGF 的基因型）对衰老对脑组织、大脑结构、神经认知和对基于运动的治疗的反应的转录谱的影响的重要数据，充分告知我们对衰老人类受试者行为变化的神经机制的理解。这个解释不仅是机械性的，而且是完全转化的，因为它首先是 1. 对 BDNF 基因型的分子理解，调节约 48000 个皮质转录本的表达模式，这是通过人类死后样本的微阵列分析确定的； 2. 检查年龄 x BDNF 基因型对结构 MRI 和神经认知中神经解剖学体积的影响，重点是情景记忆和内侧颞叶结构以及影响调节；包括 3. 一项概念验证随机试验，检查体育锻炼（旨在增加 BDNF 表达）和 BDNF 基因型对认知终点的影响。如果这些研究的预测是正确的，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力