MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

描述(申请人提供)：使用正常衰老的非人灵长类动物模型，这项研究将探索成年细胞在海马体和灵长类动物大脑周围区域发生的作用。溴脱氧尿苷(BrdU，一种细胞增殖的标志)将被注射到幼年和老年恒河猴(Macaca Mulatta)体内。在注射BrdU后，一组猴子将被赋予一项诱导神经再生的行为任务。使用免疫组织化学、体视学和共聚焦显微镜对脑组织进行尸检分析，将识别新生的神经元、星形胶质细胞和少突胶质细胞。本研究将对两组实验数据进行分析。1)新生细胞在基础条件下的分化将在幼年和老年动物身上进行检测。初步结果表明，成体细胞的发生随着年龄的增长而发生变化；这些变化的细节将被探索。2)已有研究表明，学习可以增加成人海马区的神经发生。这种可塑性将在接受后BrdU行为测试的年轻和老年动物中进行比较。人们已经证实，认知能力会随着年龄的增长而下降。这项拟议的研究将确定成人细胞发生的变化是否可能在与年龄相关的认知下降的神经生物学基础上具有重要意义。

DESCRIPTION (provided by applicant): Using a non-human primate model of normal aging, this investigation will explore the role of adult cell genesis in the hippocampus and surrounding areas of the primate brain. Bromodeoxyuridine (BrdU, a marker of cell proliferation) will be injected into both young and old rhesus monkeys (Macaca mulatta). After injection of BrdU, a subset of monkeys will be given a behavioral task to induce neurogenesis. Post-mortem analysis of brain tissue using immunohistochemistry, stereology, and confocal microscopy, will identify newly created neurons, astrocytes, and oligodendrocytes. This study will analyze two sets of experimental data. 1) Differentiation of newly created cells under basal conditions will be examined in young and old animals. Preliminary results suggest that there are changes in adult cell genesis with age; the details of these changes will be explored. 2) Learning has been shown to increase adult neurogenesis in the hippocampus. This plasticity will be compared in young and old animals that received post-BrdU behavioral testing. It has been established that cognitive decline occurs with age. This proposed investigation will determine if there are changes in adult cell genesis that could be important in the neurobiological basis of age-related cognitive decline.