HORMONAL INFLUENCES ON COGNITION

荷尔蒙对认知的影响

• 批准号: 6450696
• 负责人: VICTORIA N LUINE
• 金额: $ 5.95万
• 依托单位: HUNTER COLLEGE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6450696
• 关键词: behavior test; cognition; estrogens; female; field study; gamma aminobutyrate; high performance liquid chromatography; hormone regulation /control mechanism; in situ hybridization; laboratory rat; memory; neural transmission; neurochemistry; progesterone; radioimmunoassay; sex hormones; stereotaxic techniques

A variety of studies show that estrogen may promote memory in females, both animal and human with low estrogen levels. Moreover, estrogen may also delay or prevent the onset of Alzheimer's Disease and improve cognition in women with the disease. Using young and aged rats as models, experiments will examine effects of gonadal hormones on memory using a spatial memory task, object recognition. First, the dose- response relationship between estrogen and enhanced memory will be determined.. Whether concurrent administration of progesterone with estrogen alters the enhancing effects of estrogen on memory will be tested. Then possible enduring effects of gonadal hormones on memory will be tested, i.e., whether chronic estrogen alone or with progesterone enhances memory months after discontinuation. Effects of these hormone treatments on GABAergic and monoaminergic neurotransmission in brain areas involved in memory function will be measured by neurochemical techniques. Whether alterations in memory occur over the estrus cycle and after chronic ovariectomy will be determined and will show whether hormones exert short term effects or long term, trophic effects. Thus, proposed experiments will characterized fundamental relationships between gonadal hormones and memory function. While important for providing basic information concerning hormone actions and the neural bases for hormonal effects on memory, the studies also have significant health implications for aging and Alzheimer's disease. Concurrent estrogen and progesterone therapy is the treatment of choice for post menopausal women, but little is known about the effects of progesterone on memory. In addition, if post-menopausal hormone replacement therapy can delay dementia onset by 5 years, the incidence of dementia has been projected to decreased by 50%. Finally, if only a few years of replacement can be given with the same benefits on memory loss or in developing AD, then the risk of side effects of estrogen can be greatly minimized.

各种研究表明，雌激素可以促进女性的记忆，无论是动物还是雌激素水平低的人。此外，雌激素还可以延迟或预防阿尔茨海默病的发作，并改善患有该疾病的女性的认知能力。以年轻和老年大鼠为模型，实验将使用空间记忆任务，物体识别来检查性腺激素对记忆的影响。首先，雌激素和增强记忆之间的剂量-反应关系将被确定。同时给予孕酮和雌激素是否会改变雌激素对记忆的增强作用将被测试。然后将测试性腺激素对记忆的可能持久影响，即，无论是单独使用雌激素还是与孕激素联合使用，在停药数月后都能增强记忆力。将通过神经化学技术测量这些激素治疗对涉及记忆功能的脑区域中的GABA能和单胺能神经传递的影响。将确定在发情周期和慢性卵巢切除术后记忆是否发生改变，并将显示激素是否发挥短期作用或长期营养作用。因此，建议的实验将特征性的性腺激素和记忆功能之间的基本关系。虽然这些研究对于提供有关激素作用和激素对记忆影响的神经基础的基本信息很重要，但它们对衰老和阿尔茨海默病也有重要的健康影响。同时雌激素和孕激素治疗是绝经后妇女的治疗选择，但对孕激素对记忆的影响知之甚少。此外，如果绝经后激素替代疗法可以将痴呆症的发病时间推迟5年，那么痴呆症的发病率预计将下降50%。最后，如果只有几年的替代可以在记忆丧失或发展AD方面获得相同的好处，那么雌激素副作用的风险可以大大降低。