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.

阿尔茨海默氏病（AD）的特征是逐渐下降 认知过程，例如学习和记忆。 海马 参与学习和记忆，并受到AD患者的影响。 学习和记忆也随着正常衰老而发生。 相信 学习和记忆过程可以通过突触介导 可塑性。 这些研究的主要目的是调查 长期增强的持续时间，一种突触可塑性的形式 老化的动物及其对基因表达的影响 在学习海马依赖的空间学习和 长期在体内自由移动动物的增强。 在特定目标中 我的实验将表征年龄受损或老化的动物 在空间学习中没有受损。 动物将用于永久 内侧或外侧穿孔路径ca3中的电极植入 突触调查这些长期增强的持续时间 突触。 在特定目标中2实验将研究 许多候选基因的时间和空间mRNA表达 学习过程中的细胞色素氧化酶活性。 在老年人的受损和 老化的未损坏动物，实验将比较mRNA表达 通过使用原位杂交，HZF-3，TPA，Agrin和滞后 通过使用组织化学技术的细胞色素氧化酶的活性。 在 特定的目标3实验将研究HZF-3的mRNA表达， TPA，Agrin和LAG以及细胞色素氧化酶活性在 内侧和横向穿孔路径CA3的长期增强 突触。 拟议研究的研究结果已有 对衰老研究的重要意义。 长期存在的概念 学习和记忆是突触连接的修改 在神经系统中，可能是学习和记忆过程的基础。 如果学习过程中突触修饰的永久变化， 这些变化也必须在遗传水平上反映。 因此，如果 突触塑料的减少和基因降低 在空间学习动物的老年人中观察到表达， 然后，这与老年相关障碍之间的关系 基因表达可能会将光渗入与之相关的机制 与衰老相关的认知障碍。 此外，减少了 在学习和突触可塑性中的环状氧化酶活性 会表明该酶在认知过程中很重要。