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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，激素替代越来越普遍。最近，研究表明，雌激素和黄体酮可以影响更高层次的认知行为，在绝经后和月经周期的波动中使用。雌激素似乎还能延缓阿尔茨海默病的发作，以及调节精神分裂症的症状。这些影响的动物模型将有助于理解卵巢类固醇如何影响一生中处理高级认知功能的神经系统部分。本研究的长期目标是探讨卵巢类固醇对循环和衰老雌性大鼠认知行为和伴随神经基质的影响。在开始对激素操作进行大规模和详细的研究之前，需要寻求初步数据来选择集中在哪个神经区域。研究老龄大鼠的发情状态和年轻成年雌鼠的发情周期对脊柱密度和树突场范围的影响。两个认知相关的区域将被取样：海马体和内侧前额皮质。有初步数据表明，脊柱密度随着年龄的增长而急剧下降（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与年龄相关变化的一个很好的模型。如果它对卵巢类固醇是相对难治性的，内侧前额叶皮层的变化将是两性普遍衰老效应的有用模型。