Age/Sex Effects on the Central Serotonin System

年龄/性别对中枢血清素系统的影响

• 批准号: 7045984
• 负责人: Carolyn C Meltzer
• 金额: $ 45.77万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-05 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7045984
• 关键词: adult human (21+); age difference; bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain morphology; clinical research; cognition disorders; depression; disease /disorder proneness /risk; gender difference; human old age (65+); magnetic resonance imaging; memory disorders; neuropathology; neuropharmacology; neuropsychological tests; neuropsychology; pharmacokinetics; positron emission tomography; psychometrics; questionnaires; receptor binding; receptor expression; serotonin receptor; urinalysis

DESCRIPTION (provided by applicant): Advances in molecular biology and neuroimaging, coupled with the imperative caused by the aging of the population, have created fertile ground for improved understanding of the interaction between brain function and behavior. It is well recognized that the integrity of the central serotonin (5-HT) neurotransmitter system is essential for the proper regulation of mood, behavior, and memory. Selective age effects on the 5-HT system may impact risk and manifestations of depression across the lifespan and cognitive impairment in the elderly. Further, mood disorders and Alzheimer's disease affect a disproportionate number of women, yet the etiology and potential treatment implications of this gender association are understudied. Indeed, sex differences in the effect of age on the 5-HT system is of etiologic and therapeutic importance to potential gender influences on susceptibility, course, and treatment of mood and cognitive disturbances in normal aging and in association with neurodegenerative disease. The aim of this proposal is to define the role of aging and the potential influence of gender on serotonergic function. This study focuses on two complementary 5-HT receptor subtypes, 5-HT1A and 5-HT2A, because of their association with depression and memory function and putative role in mechanisms of antidepressant treatment response; further, these receptor subtypes are pharmacologically well-characterized and amenable to in vivo study in humans with new highly selective ligands for positron emission tomography (PET). Quantitative image analysis will include a magnetic resonance (MR) imaging-based partial volume correction developed by the PI in order to minimize the diluting effects of cerebral atrophy, a source of bias that frequently confounds PET studies of aging. The goal of this work is to provide unique and direct information on the effect of age and potential influence of sex on human serotonergic function. Thus, this revised R01 application complements our funded R01 (MH59945), which uses PET and serotonergic ligands to investigate treatment response mechanisms in late-life depression. The current proposal further reinforces the strong commitment by the PI and colleagues to apply advanced quantitative in vivo imaging techniques to define neurobiologic correlates of aging and neuropsychiatric disorders of late life.

描述（由申请人提供）：分子生物学和神经影像学的进步，加上人口老龄化带来的迫切需要，为更好地理解大脑功能和行为之间的相互作用创造了肥沃的土壤。众所周知，中枢血清素 (5-HT) 神经递质系统的完整性对于情绪、行为和记忆的正确调节至关重要。 5-HT 系统的选择性年龄效应可能会影响老年人一生中抑郁症的风险和表现以及认知障碍。此外，情绪障碍和阿尔茨海默病影响着不成比例的女性，但这种性别关联的病因和潜在的治疗影响尚未得到充分研究。事实上，年龄对 5-HT 系统影响的性别差异对于正常衰老中以及与神经退行性疾病相关的情绪和认知障碍的易感性、病程和治疗的潜在影响具有病因学和治疗重要性。 该提案的目的是确定衰老的作用以及性别对血清素功能的潜在影响。本研究重点关注两种互补的 5-HT 受体亚型：5-HT1A 和 5-HT2A，因为它们与抑郁和记忆功能相关，并且在抗抑郁治疗反应机制中发挥推定作用；此外，这些受体亚型在药理学上具有良好的特征，并且适合使用用于正电子发射断层扫描（PET）的新型高选择性配体进行人体体内研究。定量图像分析将包括由 PI 开发的基于磁共振 (MR) 成像的部分体积校正，以尽量减少脑萎缩的稀释效应，脑萎缩是经常混淆 PET 衰老研究的偏差来源。 这项工作的目标是提供关于年龄和性别对人类血清素功能的潜在影响的独特而直接的信息。因此，这个修订后的 R01 申请补充了我们资助的 R01 (MH59945)，它使用 PET 和血清素配体来研究晚年抑郁症的治疗反应机制。当前的提案进一步强化了 PI 及其同事的坚定承诺，即应用先进的定量体内成像技术来定义衰老和晚年神经精神疾病的神经生物学相关性。