Neurogenesis in an Animal Model of Cognitive Aging

神经发生在成人齿状回的观察引发了许多关于这种现象在海马体记忆功能中的作用的猜测。这一假设可能延伸到认知衰老，这一观点得到了与年龄相关的神经发生下降的报道[2,3,4]和大量证据的支持，表明衰老过程中依赖海马形成[1]的功能存在认知缺陷。然而，到目前为止，几乎没有证据表明这些新生成细胞的增殖、存活或分化率的变化对幼龄或老年动物海马相关的认知功能有影响。提出的实验将直接检查认知能力和海马衰老模型中神经发生之间的关系。具体来说，年轻、中年和老年大鼠将在Morris水迷宫任务的空间版本和评估工作记忆的延迟匹配-地点任务上表现出行为特征（具体目标1）。这些具有不同年龄行为特征的大鼠将被评估海马体中新细胞的增殖率和存活率（Specific Aim 2）。这些结果将与同一受试者嗅觉系统中获得的数据进行比较（具体目标3）。将使用额外的材料和方法来研究新生成的海马细胞分化为神经元的数量（Specific Aim 4）。神经发生的每一个方面都与认知衰老的个体差异有关。

The observation that neurogenesis occurs in the adult dentate gyrus has sparked much speculation regarding a role for this phenomenon in hippocampal mnemonic function. This hypothesis may extend to cognitive aging, an idea supported by reports of age-related declines in neurogenesis [2,3,4] and substantial evidence for cognitive deficits during aging in functions that depend on the hippocampal formation [1]. Yet, to date, there is little evidence that changes in the rate of proliferation, survival or differentiation of these newly generated cells has consequences for cognitive function associated with the hippocampus in either young or aged animals. The proposed experiments will directly examine an association between cognitive abilities and neurogenesis in a well characterized model of hippocampal aging. Specifically, young, middle-aged, and aged rats will be behaviorally characterized on the spatial version of the Morris water maze task and a delayed match-to-place task that will assess working memory (Specific Aim 1). These behaviorally characterized rats of different ages then will be evaluated for the rate of proliferation and survival of new cells in the hippocampus (Specific Aim 2). Those results will be compared to data obtained in the olfactory system in the same subjects (Specific Aim 3). Additional material and methods will be used to study the numbers of newly generated hippocampal cells that differentiate into neurons (Specific Aim 4). Each of these aspects of neurogenesis will be related to individual differences in cognitive aging.