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HORMONAL INTERACTION WITH AGING BRAIN

荷尔蒙与大脑老化的相互作用

基本信息

批准号：
6129273
负责人：
JANICE M JURASKA
金额：
$ 7.17万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-04-15 至 2002-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6129273
关键词：
Golgi apparatus aging dendrites estrogens female hippocampus hormone regulation /control mechanism laboratory rat menstrual cycle ovariectomy prefrontal lobe /cortex

项目摘要

As the proportion of post-menopausal women in the population has increased, hormone replacement has become increasingly commonplace. Recently, research has suggested that estrogens and progestins can affect higher order, cognitive behaviors when used in replacement after menopause and in their fluctuations during the menstrual cycle. Estrogens also appear to delay the onset of Alzheimer's disease, as well as modulate schizophrenic symptoms. An animal model of these effects would be useful in understanding how the ovarian steroids influence parts of the nervous system dealing with higher cognitive functions through the lifespan. The long term goal of this research is to explore the effects of ovarian steroids on cognitive behavior and concomitant neural substrates in the cycling and aging female rat. Before commencing on large and detailed studies with hormone manipulations, preliminary data are sought to select which neural area upon which to concentrate. The effects of the estropausal state of the aging rat and the phase of the cycle in young adult females on spine densities and dendritic field extent will be examined. Two cognitively relevant areas will be sampled: the hippocampus and the medial prefrontal cortex. There is preliminary data that spine densities drop precipitously with age (28-40 percent) in the medial prefrontal cortex. If this area is sensitive to ovarian hormones in aging, it would be an excellent model for age related changes in female anatomy and behavior. If it is relatively refractory to ovarian steroids, changes in the medial prefrontal cortex would be a useful model for general aging effects in both sexes.

随着绝经后妇女在人口中所占比例的增加，激素替代疗法变得越来越普遍。最近，研究表明，雌激素和孕激素可以影响更高层次的认知行为时，在绝经后使用的替代品和在月经周期期间的波动。雌激素似乎也可以延缓阿尔茨海默病的发病，以及调节精神分裂症的症状。这些作用的动物模型将有助于了解卵巢类固醇如何影响神经系统的部分，在整个生命周期中处理更高的认知功能。本研究的长期目标是探索卵巢类固醇对周期性和衰老雌性大鼠认知行为和伴随的神经底物的影响。在开始对激素操纵进行大规模和详细的研究之前，需要寻找初步的数据来选择要集中注意力的神经区域。将检查老龄大鼠的动情间期状态和年轻成年雌性的周期阶段对棘密度和树突野范围的影响。将对两个认知相关区域进行采样：海马体和内侧前额叶皮层。有初步数据表明，随着年龄的增长，内侧前额叶皮层的脊柱密度急剧下降（28%-40%）。如果这个区域在衰老过程中对卵巢激素敏感，那么它将是女性解剖学和行为学中与年龄相关的变化的极好模型。如果卵巢类固醇激素相对难治，内侧前额叶皮质的变化将是一个有用的模型，在两性的一般老化影响。