AGE AND PATHOLOGY INTERACTION IN FRONTAL CORTEX FUNCTION

额叶皮层功能中年龄和病理学的相互作用

基本信息

批准号：
2035701
负责人：
CARA L WELLMAN
金额：
$ 3.75万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-01-01 至 1998-12-31
项目状态：
已结题

项目摘要

The nucleus basalis magnocellularis (NBM) plays a role in cognition and has been implicated in behavioral changes associated with aging and with age-related pathology. Acetylcholine modulates cortical activity and plasticity; because the NBM is the major source of acetylcholine for frontal cortex, it is likely that the NBM, and lesions of the NBM, affect behavior through modulation of frontal cortical structure and function. Furthermore, NBM lesions superimposed on age-related neuronal changes may produce unique behavioral deficits and alterations in frontal cortex. Previous studies have shown that in the NBM system, aging produces unique morphological changes at different ages (Wellman et al., 1995), and that the plasticity of frontal cortical neurons changes with age (Wellman & Sengelaub, 1995). The proposed research will assess the neurochemical and behavioral correlates of these structural changes. Experiment 1 will assess performance of a radial maze task, which is sensitive to both aging and dysfunction of the NBM, in young adult, middle-aged, and aged rats with either excitotoxic or sham lesions of the NBM. Experiment 2 will assess the effects of NBM lesions on neurochemistry of frontal cortex in the young adult, middle-aged, and aged rats behaviorally characterized in Experiment 1. Potential alterations in the noradrenergic, GABAergic, cholinergic, and glutamatergic systems in frontal cortex will be assessed via quantitative autoradiography; in addition, correlations between these potential pharmacological changes and maze performance will be examined. Thus, these experiments will characterize neurochemical alterations in frontal cortex due to aging, neuropathology, and their interaction and will provide valuable data about neurochemical mechanisms of age- and pathology-related cognitive deficits.

大细胞基底核 (NBM) 在认知中发挥作用并与衰老相关的行为变化有关以及与年龄相关的病理学。乙酰胆碱调节皮质活性和可塑性；因为NBM是主要来源额叶皮质的乙酰胆碱，很可能是 NBM，并且 NBM 损伤，通过调节额叶影响行为皮质结构和功能。此外，NBM 病变叠加与年龄相关的神经元变化可能会产生独特的行为缺陷和额叶皮层的改变。以前的研究表明，在 NBM 系统中，衰老会产生独特的不同年龄的形态变化（Wellman et al., 1995），以及额叶皮层神经元的可塑性随着年龄的增长而变化（Wellman 和 Sengelaub，1995）。拟议的研究将评估这些结构变化的神经化学和行为相关性。实验 1 将评估径向迷宫任务的性能，即年轻人对衰老和 NBM 功能障碍敏感，具有兴奋性毒性或假性损伤的中年和老年大鼠 NBM。实验 2 将评估 NBM 损伤对青年、中年和老年人额叶皮层的神经化学实验 1 中老年大鼠的行为特征。潜力去甲肾上腺素能、GABA能、胆碱能和额叶皮层的谷氨酸能系统将通过以下方式进行评估定量放射自显影；此外，这些之间的相关性潜在的药理变化和迷宫性能将检查了。因此，这些实验将表征神经化学由于衰老、神经病理学及其相关因素导致的额叶皮层的变化相互作用并将提供有关神经化学的有价值的数据年龄和病理相关认知缺陷的机制。