Botanical Menopausal Therapies Mechanisms of CNS Action

描述(申请人提供)：针对更年期症状的替代植物疗法正在得到更广泛的应用，部分原因是妇女健康倡议(WHI)最近的报告称，雌激素和孕激素联合治疗会增加乳腺癌、中风和心血管疾病的风险。国家补充和替代医学中心(NCCAM)2003财年的研究重点提倡进行评估植物疗法对更年期症状的有效性的临床研究和阐明其作用机制的临床研究，最好是通过合作的随机临床试验。这项指导科学家发展奖(K01)的申请侧重于发展首席研究员的能力，使其成为补充和替代疗法影响大脑功能的机制的独立调查者。迫切需要经过高级培训的熟练临床研究人员来满足这些优先事项。这位候选人在性类固醇激素、认知和大脑功能方面带来了不同寻常的专业知识和研究经验--包括共同开发WHI认知研究 老龄化--以及与尿酸/国立卫生研究院植物性饮食中心研究人员的积极合作 妇女健康补充研究。拟议培训计划的积极研究部分首先将重点放在黑升麻和红三叶草影响神经认知功能和情绪的机制上。该奖项的具体指导活动侧重于一个三管齐下的培训计划，以发展首席研究员调查植物疗法对中枢神经系统的神经、生理和神经化学作用机制的能力。第一个活动集中在功能磁共振成像和扩散张量成像，以检查植物药物对潜在记忆性能的大脑系统的影响。第二项活动集中于使用可移动的胸骨皮肤电导监测器测量潮热，以调查植物药是否通过改善更年期症状来改善认知。第三项活动涉及实施药理学挑战方法，以检查植物疗法是否通过5-羟色胺影响中枢神经系统功能。这一培训经验的长期目标是为PI提供保护的时间和培训，以开发易于推广的技能，以研究一系列植物疗法对认知功能的影响，特别是被中心的基础科学计划确定为对中枢神经系统具有潜在有益影响的提取物。拟议的研究计划建立在UIC/NIH植物中心基础和临床研究综合计划的基础上，并向新的和及时的方向扩展其临床研究计划。对植物疗法对大脑功能的影响以及替代疗法影响认知的基本机制缺乏了解，这两方面都突显出需要培训研究人员掌握必要的技能，以推进这一领域的临床研究，并满足妇女健康研究的迫切需求。

DESCRIPTION (provided by applicant): Alternative botanical therapies for menopausal symptoms are becoming more widely used, in part due to recent reports from the Women's Health Initiative (WHI) that combined estrogen and progestin therapy increases risks for breast cancer, stroke, and cardiovascular disease. The National Center for Complementary and Alternative Medicine (NCCAM) Fiscal Year 2003 Research Priorities advocate both clinical studies evaluating the efficacy of botanical therapies for menopausal symptoms and clinical studies elucidating their mechanisms of action, optimally through collaborative randomized clinical trials. This Mentored Scientist Development Award (K01) application focuses on developing the principal investigator's ability to become an independent investigator of the mechanisms by which complementary and alternative therapies affect brain function. There is a pressing need for skilled clinical investigators with advanced training to meet those priorities. This candidate brings to this training effort uncommon expertise and research experience in sex steroid hormones, cognition, and brain function - including co-development of the WHI Study of Cognitive Aging - as well as active collaborations with investigators at the URIC/NIH Center for Botanical Dietary Supplement Research in Women's Health. The active research component of the proposed training program will initially focus on the mechanisms by which black cohosh and red clover affect neurocognitive function and mood. The specific mentored activities of this Award focus on a three-pronged training program to develop the principal investigator's ability to investigate the neural, physiological, and neurochemical mechanisms of action of botanical therapies on the CNS. The first activity focuses on functional magnetic resonance imaging and diffusion tensor imaging to examine the influence of botanicals on the brain systems underlying memory performance. The second activity focuses on the use of ambulatory sternal skin conductance monitors in the measurement of hot flushes to investigate whether botanicals improve cognition by improving menopausal symptoms. The third activity involves implementation of pharmacological challenge methods to examine whether botanical therapies act through serotonin to influence CNS function. The long-term goal of this training experience is to provide the protected time and training for the PI to develop readily generalizable skills for investigating a range of botanical therapies on cognitive function, especially extracts identified by the Center's basic science program as having potential beneficial effects on the CNS. The proposed research program builds on the UIC/NIH Botanical Center's comprehensive program of basic and clinical research and extends its clinical research program in a new and timely direction. The lack of understanding of the effects of botanical therapies on brain function and the basic mechanisms by which alternative therapies can influence cognition both underscore the need to train researchers with the necessary skills to advance clinical research in this area and address pressing needs in women's health research.