Cortical Aging, Estrogen and Behavior

皮质老化、雌激素和行为

• 批准号: 7102621
• 负责人: JANICE M JURASKA
• 金额: $ 17.74万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102621
• 关键词: acetylcholine; aging; behavior test; behavioral /social science research tag; brain mapping; brain morphology; cognition disorders; corpus callosums; dopamine; electron microscopy; estrogens; gender difference; hormone regulation /control mechanism; hormone therapy; immunocytochemistry; laboratory rat; menopause; neural degeneration; neuropsychology; ovariectomy; prefrontal lobe /cortex; progesterone; psychological aspect of aging; reversal learning

DESCRIPTION (provided by applicant): This proposal is focused on the effects of aging in the medial prefrontal cortex and associated behavior, with an emphasis on female rats and the role of estrogen and progesterone in cognitive aging. The proposal explores the hypothesis that the medial prefrontal cortex is one of the important sites for the cognitive decline associated with aging and for the actions of estrogen and progesterone on that decline. There are three issues that will be addressed here. One concerns the role of the medial prefrontal cortex in age-related cognitive decline. There has been considerable emphasis on the hippocampus in the rat because many of the cognitive behavioral tasks that show deficits in aged males are hippocampal dependent (eg, water maze, radial arm maze). The medial prefrontal cortex also is engaged in these tasks and is not as extensively studied, although there is neuro-anatomical evidence of aging in the cerebral cortex. The second topic is the characterization of aging in female rats. The literature on behavioral and neural effects of aging has, until recently, emphasized male rats. The many sex differences that have been documented in neural areas associated with cognition indicate that males and females enter the aging life phase with dimorphic nervous systems that may affect the aging process itself. The third issue concerns the efficacy of hormone replacement therapy including the mode of replacement (chronic vs cyclic hormones) on neural and behavioral aging. Ovariectomized, aged rats can provide a model for both chronic and tonic HRT on neural and behavioral aging. The recent results from the Women's Health Initiative make the studies proposed here of great clinical relevance. Hormone replacement therapy has become very common as the female population ages. It is essential to understand the effects of estrogen and progesterone on the aging process and how the effects of these hormones may be altered by different regimens of replacement. Another important aspect of clinical importance is the actions of ovarian steroids on the medial prefrontal cortex because the human analogue of this region is thought to be involved in schizophrenia. There are sex differences in the age and severity of onset of schizophrenia, and symptoms become exacerbated with menopause, which may indicate a protective role of estrogen and possibly progesterone for this region. Lastly, MRI in humans indicates changes in the volume of may neural areas with age. Exploring the cellular basis for these changes is not feasible in humans, but the aging rat can serve as a model for the types of cellular changes that underlie human aging.

描述（由申请人提供）：该建议集中于衰老在内侧前额叶皮层和相关行为中的影响，重点是雌性大鼠以及雌激素和孕激素在认知衰老中的作用。该提案探讨了以下假设：内侧前额叶皮层是与衰老相关的认知下降以及雌激素和孕激素对这种下降的作用的重要地点之一。这里将解决三个问题。一种涉及内侧前额叶皮层在与年龄相关的认知下降中的作用。大鼠的海马有很大的重视，因为许多表现出老年男性缺陷的认知行为任务都是海马依赖性的（例如，水迷宫，径向臂迷宫）。内侧前额叶皮层也参与了这些任务，但并未进行广泛研究，尽管在大脑皮层中有神经 - 动物学的证据。第二个主题是雌性大鼠衰老的表征。直到最近，关于衰老的行为和神经作用的文献都强调了雄性大鼠。与认知相关的神经区域中已记录的许多性别差异表明，男性和女性通过二态神经系统进入衰老生活阶段，可能会影响衰老过程本身。第三个问题涉及激素替代疗法的疗效，包括替代方式（慢性与环状激素）对神经和行为衰老。卵巢切除的老年大鼠可以为神经和行为衰老提供慢性和补品HRT的模型。妇女健康计划的最新结果使这里提出的研究具有很大的临床意义。随着女性人口年龄，激素替代疗法已变得非常普遍。必须了解雌激素和孕酮对衰老过程的影响以及这些激素的影响如何通过不同的替代方案改变。临床重要性的另一个重要方面是卵巢类固醇对内侧前额叶皮层的作用，因为该地区的人类类似物被认为与精神分裂症有关。精神分裂症发作的年龄和严重程度存在性别差异，更年期的症状会加剧，这可能表明雌激素的保护作用以及该地区可能的孕激素。最后，人类的MRI表明随着年龄的增长，5月神经区域的体积发生变化。在人类中探索这些变化的细胞基础是不可行的，但是老化的大鼠可以作为人类衰老构成细胞变化类型的模型。