Aging and Memory

描述（由申请人提供）：葡萄糖管理增强啮齿动物和人类的学习和记忆，并在逆转与年龄相关的记忆损伤方面特别有效。该研究项目将研究与年龄相关的血液和大脑葡萄糖调节的变化是否会导致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，这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耦，导致循环葡萄糖水平对训练的反应减弱。血糖水平的降低可能会显著影响大脑对学习和记忆的重要过程。在大脑中，当大鼠在海马体依赖的自发交替任务中进行测试时，海马体中的细胞外葡萄糖水平被耗尽。与年轻的成年大鼠相比，年老的大鼠在这项任务中表现不佳，在行为测试中，海马区葡萄糖消耗过度。注射（i.p）葡萄糖可阻断老年大鼠海马的耗竭并提高其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控制的改变可能会导致与年龄相关的记忆损伤。该实验将使用年轻和年老的大鼠，研究葡萄糖对训练反应的年龄相关变化对学习和记忆的年龄相关变化的贡献。拟议的实验将检查老年大鼠在训练后循环和脑葡萄糖反应的变化，评估这些变化与学习和记忆的关系。实验将确定老年大鼠海马细胞外葡萄糖水平的降低是否在纹状体和前额皮质也很明显。这些实验包括测量在训练过程中细胞外脑葡萄糖水平的变化，并评估直接向训练中葡萄糖消耗殆尽的大脑区域注射葡萄糖的效果，这些治疗可以增强老年大鼠的学习和记忆能力。

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.