AGED-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: 3802175
• 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/3802175
• 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.

此项目是对上一次提交的项目3的修改 它侧重于与年龄相关的形态和神经化学变化 灵长类基底前脑和颞叶边缘系统的状态 大脑。本项目已扩大到包括其他 解决细胞衰老相关变化的化学神经解剖学技术 高亲和力摄取部位的数量、传入神经和密度 以及所有主要神经化学物质的突触前和突触后受体 神经支配而不是细胞损失形成的结构和化学 与年龄相关的认知衰退的基础，包括记忆障碍。 这一假设将通过解决以下具体问题来进行研究 与年龄相关的颞叶边缘系统改变的目的：(1) 以确定细胞的内在或范围是否存在选择性丢失 死亡或萎缩，(2)确定是否存在选择性损失 内源性或外源性GABA能神经元，(3)确定是否有 神经纤维束的改变，(4)以确定是否有丢失或 突触形态改变，(5)确定是否有改变 高亲和力神经递质摄取的密度和分布 地点，(6)确定密度是否有变化和 突触前和突触后受体的分布，(7)确定 大脑皮层大细胞神经元丢失的时程和特点 基底前脑。此外，在项目2和项目3的协作下， 另一个目标将是确定与年龄有关的密度和 突触前、后高亲和力摄取部位的分布 背外侧前额叶联合皮质的受体，以及 与项目5协作，以确定这些相同内容中的更改 神经递质水平。为了实现这些具体目标，一种组合 光学和电子显微镜测量和体外最新技术 将利用配体结合技术。以这种方式，在相同的 与年龄相关的结构和化学神经解剖学变化 可发生在基底前脑和颞叶边缘系统 与记忆障碍和其他认知功能障碍有关。