Hormonal Influences on Cognition

荷尔蒙对认知的影响

• 批准号: 6773119
• 负责人: VICTORIA N LUINE
• 金额: $ 8.2万
• 依托单位: HUNTER COLLEGE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6773119
• 关键词: behavioral /social science research tag; brain morphology; developmental neurobiology; estrogen receptors; gender difference; hormone regulation /control mechanism; laboratory mouse; laboratory rat; long term memory; memory; neuroprotectants; sex hormones; short term memory; space perception; visual perception

DESCRIPTION (provided by applicant): It is now well accepted that gonadal steroids exert potent influences in the brain during critical developmental periods and into adulthood by organizing and reorganizing the circuitry involved in neuroendocrine and behavioral functions. More recently, estradiol has also been shown to act in regions outside the neuroendocrine axis and to exert neuroprotective and neurotrophic actions on neurons. These effects are especially prominent in postmenopausal women where hormonal replacement ameliorates cognitive decline and decreases the incidence and delays the onset of several neurodegenerative diseases. With the demonstration by the Women's Health Initiative Study that current gonadal hormone replacement regimens lead to adverse effects and cancellation of one major treatment arm, it has become critical to understand how estrogen exerts its positive actions in the brain (and other tissues) and to design better hormone replacement regimens. Proposed experiments will utilize rat and mice models to investigate enhancement of recognition memory (visual and place) by estrogens and androgens. Hormones and drugs will be utilized to determine which estrogen receptors mediate the short term (non-genomic) and long term (genomic effects) enhancements of object recognition (visual memory) and object placement (spatial memory). Mice lacking specific receptors for estrogen will also be examined with these memory tasks. Mechanisms mediating estrogen-dependent enhancements in memory will be determined by use of Golgi techniques to determine hormonal effects on dendritic morphology and spine density in cortical and hippocampal neurons which are known to be important for memory. Whether gonadal hormones contribute to memory function in males will also be examined by the same behavioral and anatomical techniques. Proposed studies have enormous health relevance since age and disease related dementia is growing in the U.S. due to the aging of post war "baby boom" generations. Proposed experiments should provide better understanding of the mechanisms for gonadal hormone action and thereby provide insights for designing new hormones/drugs for the prevention and treatment of age and neurodegenerative disease related memory impairments.

描述（由申请人提供）：现在接受性腺类固醇施加强大 通过组织和 重组参与神经内分泌和行为功能的电路。最近，还显示雌二醇在神经内分泌轴外的区域起作用，并在神经元上发挥神经保护作用和神经营养作用。这些影响在绝经后妇女中尤为突出，激素替代可以缓解认知能力下降并降低发病率并延迟几种神经退行性疾病的发作。通过妇女健康倡议研究的证明，当前的性腺激素替代方案会导致不良反应和取消一个主要治疗部门，因此了解雌激素如何在大脑（和其他组织）中施加积极作用并设计更好的激素替代方案已变得至关重要。提出的实验将利用大鼠和小鼠模型来研究雌激素和雄激素对识别记忆（视觉和位置）的增强。激素和药物将用于确定哪些雌激素受体介导了对象识别（视觉记忆）和对象放置（空间记忆）的短期（非基因组）和长期（基因组效应）的增强。缺乏特定受体的雌激素受体的小鼠也将通过这些记忆任务进行检查。介导雌激素依赖性增强的机制将通过使用高尔基技术来确定对皮质和海马神经元的树突形态和脊柱密度的荷尔蒙作用，这对于记忆很重要。性腺激素是否 同样的行为和解剖技术也将对男性的记忆功能做出贡献。自年龄和疾病与疾病相关的痴呆症以来，由于战后“婴儿繁荣”一代的老龄化，拟议的研究具有巨大的健康相关性。拟议的实验应更好地了解性腺激素作用的机制，从而为设计新的激素/药物提供预防和治疗年龄和神经退行性疾病相关记忆障碍的见解。