Neurogenesis in an Animal Model of Cognitive Aging

神经发生发生在成年人齿状回的观察引发了许多关于海马记忆功能中这种现象的作用的猜测。这一假设可能扩展到认知老化，这一观点得到了神经发生中与年龄相关的下降的报告[2，3，4]以及依赖于海马结构的功能在老化期间认知缺陷的大量证据的支持[1]。然而，到目前为止，几乎没有证据表明，这些新生成的细胞的增殖，存活或分化速度的变化对与年轻或老年动物海马体相关的认知功能有影响。拟议的实验将直接检查认知能力和海马老化模型中的神经发生之间的关联。具体而言，将在空间版本的Morris水迷宫任务和延迟匹配位置任务（将评估工作记忆）上对年轻、中年和老年大鼠进行行为表征（具体目标1）。然后评价这些行为表征的不同年龄大鼠的海马中新细胞的增殖和存活率（具体目标2）。将这些结果与相同受试者的嗅觉系统中获得的数据进行比较（具体目标3）。其他材料和方法将用于研究分化为神经元的新生成海马细胞的数量（具体目标4）。神经发生的每个方面都与认知老化的个体差异有关。

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.