AGE-RELATED CHANGES IN THE LIMBIC SYSTEM OF THE PRIMATE BRAIN

灵长类大脑边缘系统与年龄相关的变化

• 批准号: 3745415
• 负责人: DOUGLAS L ROSENE
• 金额: --
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3745415
• 关键词: Macaca mulatta; acetylcholinesterase; aging; amygdala; animal age group; animal old age; axon; brain; brain mapping; cell death; cell sorting; choline; cognition disorders; cryostat; dendrites; electron microscopy; ethology; gamma aminobutyrate; hippocampus; histochemistry /cytochemistry; innervation; juvenile animal; limbic system; lipofuscin; memory disorders; mitochondria; neuroanatomy; neurochemistry; neurons; neuropil; neurotransmitter receptor; prosencephalon; receptor binding; stainings; synapses; temporal lobe /cortex

This project is a modification of Project 3 from the previous submission which focuses on age-related changes in the morphological and neurochemical state of the basal forebrain and temporal lobe limbic system of the primate brain. The present project has been expanded to include additional chemical neuroanatomical techniques to address age-related changes in cell number, afferent innervation and, density of high affinity uptakes sites and pre- and postsynaptic receptors of all of the major neurochemical innervation rather than cell loss form the structural and chemical substrates of age-related cognitive decline including memory impairment. This hypothesis will be investigated by addressing the following specific aims concerning age-related changes in the temporal lobe limbic system: (1) to determine if there is a selective loss in intrinsic or extent of cell death or shrinkage, (2) to determine if there is a selective loss in intrinsic or extrinsic GABAergic neurons, (3) to determine if there are alterations in the neuropil, (4) to determine whether there is a loss or altered morphology of synapses, (5) to determine if there are alterations in the density and distribution of high affinity neurotransmitter uptake sites, (6) to determine whether there are alterations in the density and distribution of pre- and postsynaptic receptors, (7) to determine whether the time course and features of the loss of magnocellular neurons of the basal forebrain. Furthermore, in collaboration with Projects 2 and 3, another aim will be to determine the age-related changes in the density and distribution of high affinity uptake sites and pre- and postsynaptic receptors in the dorsolateral prefrontal association cortex, and in collaboration with Project 5, to determine changes in these same neurotransmitter levels. To accomplish these specific aims, a combination of light and electronmicroscopic measures and state-of-the-art in vitro ligand binding techniques will be utilized. In this way, within the same animal the age-related structural and chemical neuroanatomical changes that occur in the basal forebrain and temporal lobe limbic system can be correlated with memory impairments and other cognitive dysfunctions.

该项目是对先前提交的项目3的修改 重点是形态学和神经化学的年龄相关变化 灵长类动物的基础前脑和颞叶边缘系统的状态 脑。 本项目已扩展到包括附加的 化学神经解剖技术解决细胞与年龄相关的变化 数量，传入神经和高亲和力摄取站点的密度 以及所有主要神经化学的前和突触后受体 神经而不是细胞损失形成结构和化学 与年龄相关的认知下降的底物，包括记忆障碍。 该假设将通过解决以下特定的研究来研究 有关颞叶边缘系统与年龄相关的变化的目的：（1） 确定固有或细胞范围是否存在选择性损失 死亡或收缩，（2）确定是否有选择性损失 固有或外在的GABA能神经元，（3）确定是否存在 神经肽的改变，（4）确定是损失还是 突触的形态改变，（5）确定是否存在改变 在高亲和力神经递质摄取的密度和分布中 站点，（6）确定密度是否发生了变化和 （7）的分布前和突触后受体的分布 时间过程和特征的损失的特征 基础前脑。 此外，与项目2和3合作 另一个目的是确定与年龄相关的密度变化和 高亲和力摄取站点以及突触前后的分布 背外侧前额叶缔合皮质中的受体，在 与项目5合作，以确定相同的变化 神经递质水平。 为了实现这些特定目标，结合了 光和电子显微镜措施和最新的体外措施 配体结合技术将被使用。 这样，在同一方面 动物与年龄有关的结构和化学神经解剖学变化 发生在基础前脑和颞叶边缘系统中 与记忆障碍和其他认知功能障碍相关。