Aging and Memory

描述(由申请人提供)：给予葡萄糖可增强啮齿动物和人类的学习和记忆，在逆转与年龄相关的记忆障碍方面尤其有效。这项研究项目将研究与年龄相关的血糖和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。训练经常伴随着循环肾上腺素水平的增加，随后循环血糖水平也会增加，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，肾上腺髓质释放的肾上腺素与随后的血糖水平上升之间存在解偶联，导致循环血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对学习和记忆至关重要的大脑过程。在大脑中，当大鼠接受依赖于海马体的自发交替任务时，海马体内的细胞外葡萄糖水平会耗尽。与年轻的成年大鼠相比，老年大鼠在这项任务中表现不佳，在行为测试中表现出海马体中葡萄糖的过度消耗。注射(Ip)葡萄糖阻断了海马区的耗竭，也提高了老年大鼠在交替任务中的表现。综上所述，这些发现表明，在衰老过程中，对血液和大脑中葡萄糖水平的控制发生变化，可能会导致与年龄相关的记忆障碍。利用年轻和老年大鼠，拟议的实验将检验与年龄相关的血糖对训练反应的变化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区细胞外葡萄糖水平的耗竭是否在纹状体和前额叶皮质也明显存在，这种情况在老年大鼠中表现得尤为明显。这些实验包括测量训练期间细胞外大脑葡萄糖水平的变化，以及评估直接向训练耗尽葡萄糖的大脑区域微量注射葡萄糖在增强老年大鼠学习和记忆方面的有效性。

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.