Aging and Memory

衰老与记忆

• 批准号: 6780862
• 负责人: PAUL E. GOLD
• 金额: $ 29.88万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6780862
• 关键词: adrenal medulla hormone; age difference; aging; animal old age; behavior test; behavioral /social science research tag; bioenergetics; blood glucose; brain mapping; brain metabolism; corpus striatum; epinephrine; hippocampus; hormone regulation /control mechanism; laboratory rat; learning; memory; microinjections; prefrontal lobe /cortex

DESCRIPTION (provided by applicant): Administration of glucose enhances learning and memory in rodents and humans, and is especially effective in reversing age-related impairments in memory. This research project will examine whether age-related changes in the regulation of blood and brain glucose contribute to age-related impairments of learning and memory. Training is often accompanied by increases in circulating epinephrine levels, with subsequent increases in circulating glucose levels, in a manner related to endogenous modulation of learning and memory. Recent evidence suggests that, in aged male Fischer 344 rats, there is an uncoupling between epinephrine release from the adrenal medulla and subsequent increases in blood glucose levels, resulting in diminished responses of circulating glucose levels to training. The reduced responses of blood glucose levels may significantly influence brain processes important for learning and memory. In the brain, extracellular glucose levels in the hippocampus are depleted while rats are tested on a hippocampus dependent spontaneous alternation task. As compared to young adult rats, aged rats perform poorly on this task and exhibit exaggerated depletion of glucose in the hippocampus during behavioral testing. Injections (i.p.) of glucose block the depletion in the hippocampus and also enhance performance on the alternation task in aged rats. Together, these findings suggest that altered control of glucose levels in blood and brain during aging may contribute to age-related impairments of memory. Using young and old rats, the proposed experiments will examine the contribution of age-related changes in responses of glucose to training to age-related changes in learning and memory. Proposed experiments will examine changes in circulating and brain glucose responses to training in aged rats, assessing the relationship of these changes to learning and memory. The experiments will determine whether the depletion of extracellular glucose levels in the hippocampus, prominent in aged rats, is evident also in the striatum and prefrontal cortex. These experiments include measures of changes in extracellular brain glucose levels during training with and without treatments that enhance learning and memory in aged rats and also assess the efficacy in enhancing learning and memory of microinjections of glucose directly into those brain areas in which glucose is depleted by training.

描述（由申请人提供）：葡萄糖的给药可增强啮齿动物和人类的学习和记忆，并且在逆转与年龄相关的记忆障碍方面特别有效。该研究项目将研究与年龄相关的血液和脑葡萄糖调节变化是否有助于与年龄相关的学习和记忆障碍。训练通常伴随着循环肾上腺素水平的增加，随后循环葡萄糖水平的增加，与内源性的学习和记忆有关。最近的证据表明，在老年男性Fischer 344只大鼠中，肾上腺素从肾上腺髓质释放与随后的血糖水平增加，导致循环葡萄糖水平对训练的反应减少。血糖水平的降低可能会显着影响对学习和记忆重要的脑过程。在大脑中，海马中的细胞外葡萄糖水平耗尽，而大鼠在海马依赖性自发交替任务上进行了测试。与年轻大鼠相比，年龄大鼠在这项任务上的表现不佳，并且在行为测试期间在海马中表现出夸张的葡萄糖耗尽。葡萄糖的注射（i.p.）阻止了海马中的耗竭，并增强了老年大鼠交替任务的性能。总之，这些发现表明，衰老过程中对血液和大脑中葡萄糖水平的控制改变可能导致与年龄相关的记忆障碍。提出的实验将使用年龄大鼠，将研究与年龄相关的葡萄糖反应变化对训练对与年龄相关的学习和记忆变化的贡献。拟议的实验将检查循环和脑葡萄糖对老年大鼠训练的反应的变化，以评估这些变化与学习和记忆的关系。实验将确定在纹状体和前额叶皮层中也很明显，在老年大鼠中突出的海马中细胞外葡萄糖水平的耗竭是否也很明显。这些实验包括训练期间和没有治疗的细胞外脑葡萄糖水平变化的措施，从而可以增强老年大鼠的学习和记忆力，并评估直接进入葡萄糖的学习和对葡萄糖显微注射的记忆的功效，直接进入葡萄糖通过训练耗尽葡萄糖的大脑区域。