Cortical Aging, Estrogen and Behavior

皮质老化、雌激素和行为

• 批准号: 6867201
• 负责人: JANICE M JURASKA
• 金额: $ 17.67万
• 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/6867201
• 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）：该提案的重点是内侧前额叶皮层衰老和相关行为的影响，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。该提案探讨了这样的假设：内侧前额叶皮层是与衰老相关的认知能力下降的重要部位之一，也是雌激素和孕激素对这种下降的作用的重要部位之一。这里要解决三个问题。其中之一涉及内侧前额叶皮层在与年龄相关的认知能力下降中的作用。人们非常重视大鼠的海马体，因为老年雄性中表现出缺陷的许多认知行为任务都依赖于海马体（例如，水迷宫、径向臂迷宫）。内侧前额叶皮层也参与这些任务，但并未得到广泛研究，尽管有大脑皮层衰老的神经解剖学证据。第二个主题是雌性大鼠衰老的特征。直到最近，有关衰老对行为和神经影响的文献一直强调雄性老鼠。与认知相关的神经区域已记录的许多性别差异表明，男性和女性进入衰老生命阶段时，神经系统具有二态性，这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功效，包括替代模式（慢性激素与周期性激素）对神经和行为衰老的影响。切除卵巢的老年大鼠可以为神经和行为衰老的慢性和强直性激素替代治疗提供模型。妇女健康倡议的最新结果使这里提出的研究具有很大的临床意义。随着女性人口老龄化，激素替代疗法变得非常普遍。了解雌激素和孕激素对衰老过程的影响以及不同的替代方案如何改变这些激素的影响至关重要。临床重要性的另一个重要方面是卵巢类固醇对内侧前额皮质的作用，因为该区域的人类类似物被认为与精神分裂症有关。精神分裂症的发病年龄和严重程度存在性别差异，并且症状随着更年期而加剧，这可能表明雌激素和孕激素对该区域的保护作用。最后，人类的核磁共振显示许多神经区域的体积随着年龄的变化而变化。探索这些变化的细胞基础在人类中是不可行的，但衰老大鼠可以作为人类衰老背后的细胞变化类型的模型。