Alzheimer's disease: the impact of age-related changes in reproductive hormones.
Alzheimer's disease: the impact of age-related changes in reproductive hormones.
复制标题
阿尔茨海默病：与年龄相关的生殖激素变化的影响。
DOI：
10.1007/s00018-004-4380-4
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Atwood,CS
中科院分区：
文献类型：
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作者：
Atwood,CS
在过去的20年里，关于荷尔蒙在健康和疾病期间调节大脑结构和功能中所起作用的研究呈指数级增长。在此期间，下丘脑-脑垂体性腺(HPG)轴激素对大脑功能的影响的研究在很大程度上是由流行病学研究推动的，这些研究表明，阿尔茨海默病(AD；2：1女性对男性)[1，2]、帕金森病(1：1.5女性对男性)[3]、多发性硬化症(2：1女性对男性)[4]和肌萎缩侧索硬化症(1：1.3女性对男性)[5]等神经退行性疾病的发病率、症状和预后存在性别依赖性。即使考虑到女性比男性长寿的事实，女性在特定年龄的AD死亡率似乎也一直较高[1]。这些发现表明，衰老过程中血清激素的性别变化是促进神经退化的常见机制。沿着这一与年龄相关的激素驱动的神经变化连续体，遗传和环境因素都将影响谁将经历与年龄相关的正常脑功能变化，而不是那些将发展为中枢神经系统疾病的人。这篇多作者的综述旨在提供我们目前关于生殖激素(即HPG轴的激素)在调节健康和疾病中的大脑结构和功能方面的作用的概述。第一篇综述(Vadakkadath Methal和Atwood)概述了HPG轴、HPG激素在生长发育、成人生殖生活和衰老过程中血清浓度的变化、HPG激素受体在大脑中的定位以及HPG激素如何通过受体和非受体介导的机制影响大脑的正常结构(神经发生、突触发生和可塑性)和功能(认知记忆、行为)。最后，讨论了在绝经和雄停经后HPG轴的失调对大脑信号的变化。随后的综述根据这些生殖后HPG轴激素的变化来检查与年龄相关的神经退行性变化。流行病学研究支持了性类固醇在推动神经退行性变化方面的作用，因为已经发现：(I)AD与绝经/雄停经后雌激素/雄激素水平下降呈正相关；(Ii)与男性相比，女性的性腺功能突然丧失得更早，与女性AD患病率的增加相关；(Iii)在接受激素替代疗法(HRT)的女性中，AD的发病率普遍下降，并延迟发病。Simpkins和他的同事回顾了基础和临床文献，这些文献表明，急性雌激素和孕激素治疗作为一种神经保护疗法用于脑缺血治疗，而慢性雌激素和/或孕激素治疗作为一种潜在的AD预防措施。正如这些作者指出的那样，急性性类固醇的使用可能是中风的一种治疗辅助手段，这一点变得越来越明显。最近，雄激素在神经退化过程中的作用得到了越来越多的关注，Bates，Martins和他的同事回顾了睾酮、脱氢表雄酮和相关的性类固醇对男性大脑认知功能的影响，以及雄激素调节认知功能的各种机制。越来越多的证据表明，雄激素的丢失会导致AD和中风等脑血管疾病。这些作者包括一个耐人寻味的章节，内容是关于变性人中的雄激素和认知，…
Over the last 2 decades, research into the role that hormones play in regulating brain structure and function during health and disease has increased exponentially. Research into the influence of hypothalamic-pituitarygonadal (HPG) axis hormones on brain function during this time has been largely driven by epidemiological studies that have demonstrated a gender dependence in the prevalence, symptomatology and prognosis of neurodegenerative diseases such as Alzheimer’s disease (AD; 2: 1 female to male)[1, 2], Parkinson’s disease (1: 1.5 female to male)[3], multiple sclerosis (2: 1 female to male)[4] and amyotrophic lateral sclerosis (1: 1.3 female to male)[5]. Even taking into account the fact that women live longer than men, women appear to have consistently higher age-specific AD death rates [1]. These findings suggest gender-specific changes in serum hormones during aging as a common mechanism promoting neurodegeneration. Along this age-related hormonally driven continuum of neurological change, both genetic and environmental factors will influence who will experience ‘normal’age-related changes in brain function versus those who will develop a central nervous system disease. This multi-author review is intended to provide an overview of our current knowledge on the role of reproductive hormones (ie hormones of the HPG axis) in regulating brain structure and function in health and in disease. The first review (Vadakkadath Meethal and Atwood) provides an overview of the HPG axis, the changes in serum concentration of HPG hormones during growth and development, adult reproductive life and senescence, HPG hormone receptor localization throughout the brain and how HPG hormones signal via receptorand non-receptor-mediated mechanisms to affect the normal structure (neurogenesis, synaptogenesis and plasticity) and functioning (cognitive–memory, behavior) of the brain. Lastly, changes in signaling to the brain with the dysregulation of the HPG axis following menopause and andropause are discussed. The reviews that follow examine age-related neurodegeneration in light of these post-reproductive alterations in HPG axis hormones.Epidemiological studies have provided support for sex steroids in driving neurodegenerative changes with aging since it has been found that there is (i) a positive relationship between AD and decreased estrogen/androgen levels after menopause/andropause;(ii) an abrupt earlier loss of gonadal function in females compared with males, correlating with the increased prevalence rate of AD in women; and (iii) a generally decreased incidence and delay in the onset of AD among women on hormone replacement therapies (HRT) after menopause. The basic and clinical literature indicating the potential of acute estrogen and progestin administration as a neuroprotective therapy for ischemia and chronic estrogen and/or progestin therapy as a potential preventative of AD is reviewed by Simpkins and colleagues. As these authors indicate it is becoming clear that the acute use of sex steroids may be a therapeutic adjunct for stroke. More recently, the role of androgens in neurodegenerative processes has gained increasing attention, and Bates, Martins and colleagues review the effects of testosterone, dehydroepiandrosterone, and related sex steroids on cognitive function in the male brain, together with the various mechanisms by which androgens may modulate cognitive function. Increasing evidence indicates that the loss of androgens leads to AD and cerebrovascular diseases such as stroke. These authors include an intriguing section on androgens and cognition in transsexuals that …