Estrogens and age-related memory decline in rodents: what have we learned and where do we go from here?
Estrogens and age-related memory decline in rodents: what have we learned and where do we go from here?
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DOI：
10.1016/j.yhbeh.2008.08.015
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发表时间：
2009-01
影响因子：
3.5
通讯作者：
Frick KM
中科院分区：
文献类型：
--
作者：
Frick KM
卵巢激素治疗是否能预防或减少绝经期妇女与年龄相关的记忆力下降的问题最近一直是争论的主题。尽管许多研究已经证明了雌激素和/或孕酮治疗对绝经期妇女某些类型的记忆的有益作用，但最近的临床试验表明，这种治疗实际上增加了认知能力下降和痴呆的风险。由于啮齿动物模型已被频繁用于检查年龄和/或卵巢激素缺乏对记忆功能的影响，年龄相关的激素和记忆衰退的啮齿动物模型可能有助于解决这个问题。本综述将集中在证据表明，雌二醇调节记忆，特别是海马依赖的记忆，在年轻和老年雌性大鼠和小鼠。影响老年女性对雌二醇记忆反应的各种因素将被强调，以说明老年女性雌激素治疗研究固有的并发症。还将讨论雌二醇为基础的疗法的未来发展的途径，有人认为，基于识别雌激素调节记忆的分子机制的药物开发方法可能会导致有前途的未来治疗减少年龄相关的记忆衰退。
The question of whether ovarian hormone therapy can prevent or reduce age-related memory decline in menopausal women has been the subject of much recent debate. Although numerous studies have demonstrated a beneficial effect of estrogen and/or progestin therapy for certain types of memory in menopausal women, recent clinical trials suggest that such therapy actually increases the risk of cognitive decline and dementia. Because rodent models have been frequently used to examine the effects of age and/or ovarian hormone deficiency on mnemonic function, rodent models of age-related hormone and memory decline may be useful in helping to resolve this issue. This review will focus on evidence suggesting that estradiol modulates memory, particularly hippocampal-dependent memory, in young and aging female rats and mice. Various factors affecting the mnemonic response to estradiol in aging females will be highlighted to illustrate the complications inherent to studies of estrogen therapy in aging females. Avenues for future development of estradiol-based therapies will also be discussed, and it is argued that an approach to drug development based on identifying the molecular mechanisms underlying estrogenic modulation of memory may lead to promising future treatments for reducing age-related mnemonic decline.