AGING & GENES IN LEARNING & LONG TERM POTENTIATION: ALZHEIMERS

老化

• 批准号: 6355380
• 负责人: EDWIN J BAREA-RODRIGUEZ
• 金额: $ 12.7万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6355380
• 关键词: aging; biotechnology; enzymes; gene therapy; genetics; minority institution research support; nervous system

Alzheimer's disease (AD) is characterized by a progressive decline of cognitive processes such as learning and memory. The hippocampus is involved in learning and memory and is affected in AD patients. Learning and memory also occurs with normal aging. It is believed that learning and memory processes may be mediated by synaptic plasticity. The major goal of these studies is to investigate the duration of long-term potentiation, a form of synaptic plasticity in the aged impaired animals and the effect of aging on gene expression during learning of a hippocampal-dependent spatial learning and long-term potentiation in vivo freely moving animals. In Specific Aim I experiments will characterize animals that are aged impaired or aged unimpaired in spatial learning. Animals will be used for permanent electrode implantation in the medial or lateral perforant path-CA3 synapse to investigate the duration of long-term potentiation at these synapses. In Specific Aim 2 experiments will investigat e the temporal and spatial mRNA expression of a number of candidate genes and cytochrome oxidase activity during learning. In aged impaired and aged unimpaired animals, experiments will compare the mRNA expression of hzf-3, tPA, agrin, and LAG by using in situ hybridization, and the activity of cytochrome oxidase by using histochemical techniques. In Specific Aim 3 experiments will investigate mRNA expression of hzf-3, tPA , agrin and LAG and the activity of cytochrome oxidase activity in long-term potentiation in the medial and lateral perforant path-CA3 synapse. The research findings from the proposed studies have important implications to aging research. A long-standing notion in learning and memory is that modifications of synaptic connections within the nervous system may underlie learning and memory processes. If permanent changes in synaptic modifications occur during learning, these changes must also be reflected at the genetic level. Thus if both a decrease in synaptic plastic ity and a decrease in gene expression is observed in aged impaired in spatial learning animals, then this a relationship between aged related impairment in learning and gene expression may shed light into the mechanisms associated with cognitive impairment associated with aging. Further, a decrease in.'cytochrome oxidase activity in learning and synaptic plasticity will suggest that this enzyme is important in cognitive processes.

阿尔茨海默病 (AD) 的特点是进行性衰退 认知过程，例如学习和记忆。 海马体 参与学习和记忆，并在 AD 患者中受到影响。 学习和记忆也会随着正常衰老而发生。 据信 学习和记忆过程可能是由突触介导的 可塑性。 这些研究的主要目标是调查 长时程增强的持续时间，突触可塑性的一种形式 老年受损动物以及衰老对基因表达的影响 在海马依赖性空间学习的学习过程中 自由活动动物体内的长时程增强作用。 特定目标 I 实验将表征老年受损或衰老的动物 空间学习未受影响。 动物将被永久使用 电极植入内侧或外侧穿通路径-CA3 突触来研究这些区域的长期增强的持续时间 突触。 在具体目标 2 中，实验将研究 多个候选基因的时间和空间 mRNA 表达 和学习过程中细胞色素氧化酶的活性。 在老年受损和 老年未受损动物，实验将比较 mRNA 表达 通过原位杂交对 hzf-3、tPA、agrin 和 LAG 进行分析， 使用组织化学技术检测细胞色素氧化酶的活性。 在 具体目标 3 实验将研究 hzf-3 的 mRNA 表达， tPA、集聚蛋白和LAG以及细胞色素氧化酶活性 内侧和外侧穿支路径的长时程增强-CA3 突触。 拟议研究的研究结果 对衰老研究具有重要意义。 长期以来的一个观念是 学习和记忆是突触连接的改变 神经系统内可能是学习和记忆过程的基础。 如果学习过程中突触修饰发生永久性变化， 这些变化也必须反映在基因水平上。 因此如果 突触可塑性下降和基因减少 在老年空间学习障碍动物中观察到表达， 那么这是与年龄相关的学习障碍之间的关系 基因表达可能揭示与相关的机制 与衰老相关的认知障碍。 此外，减少 in.'学习和突触可塑性中的细胞色素氧化酶活性 表明这种酶在认知过程中很重要。