Neurogenesis in an Animal Model of Cognitive Aging

神经发生发生在成年齿状回的观察引发了许多关于这一现象在海马区助记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告[2，3，4]的支持，以及依赖于海马体结构的功能在衰老过程中认知缺陷的大量证据[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会对幼年或老年动物的海马体相关的认知功能产生影响。拟议中的实验将直接检验认知能力和海马体衰老模型中神经发生之间的联系。具体来说，年轻、中年和老年大鼠将在空间版的Morris水迷宫任务和延迟的匹配地点任务上表现出行为特征，该任务将评估工作记忆(特定目标1)。然后将对不同年龄的这些行为特征的大鼠进行海马区新细胞的增殖率和存活率评估(特定目标2)。这些结果将与相同受试者在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新生成的分化为神经元的海马细胞的数量(具体目标4)。神经发生的每一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.