Aging and Memory

描述（由申请人提供）：给予葡萄糖可增强啮齿类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。这项研究项目将研究与年龄相关的血液和大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增加，其方式与学习和记忆的内源性调节有关。最近的证据表明，在老年雄性Fischer 344大鼠中，肾上腺髓质的肾上腺素释放与随后的血糖水平升高之间存在解偶联，导致循环葡萄糖水平对训练的反应减弱。降低血糖水平的反应可能会显著影响对学习和记忆重要的大脑过程。在脑中，海马中的细胞外葡萄糖水平被耗尽，同时对大鼠进行海马依赖性自发交替任务测试。与年轻的成年大鼠相比，老年大鼠在这项任务上表现不佳，并且在行为测试期间表现出海马体中葡萄糖的过度消耗。注射（i.p.）葡萄糖阻断老年大鼠海马的消耗，并增强老年大鼠在交替任务中的表现。总之，这些发现表明，在衰老过程中，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。使用年轻和老年大鼠，拟议的实验将检查葡萄糖对训练的响应中与年龄相关的变化对学习和记忆中与年龄相关的变化的贡献。拟议的实验将检查老年大鼠对训练的循环和大脑葡萄糖反应的变化，评估这些变化与学习和记忆的关系。这些实验将确定海马体中细胞外葡萄糖水平的消耗（在老年大鼠中突出）是否在纹状体和前额皮质中也是明显的。这些实验包括测量在有和没有增强老年大鼠学习和记忆的治疗的训练期间细胞外脑葡萄糖水平的变化，并且还评估将葡萄糖直接显微注射到其中葡萄糖被训练耗尽的那些脑区域中在增强学习和记忆方面的功效。

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.