Functional aspects of estrogen neuroprotection
Functional aspects of estrogen neuroprotection
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DOI：
10.1385/endo:21:1:33
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发表时间：
2003-06-01
期刊：
影响因子：
3.7
通讯作者：
Luine, VN
中科院分区：
文献类型：
--
作者：
Bisagno, V;Bowman, RE;Luine, VN
雌激素保护神经元免受毒性/缺血损伤或退化/衰老过程的证据在各种体外和体内系统中都是明显的。然而，一个关键的遗留问题是：雌激素所显示的形态和神经化学保护是否能够保护大脑功能或增强恢复能力？到目前为止，关于这个问题的基础研究很少。认知是一个关键的功能，它可能提供一种敏感的方式来研究这个问题。作为第一步，我们提出的结果表明，两种慢性环境侮辱，精神活性药物和压力，会在认知能力上产生性别特有的反应。具体地说，在长期接触这些因素后，女性似乎比男性对认知障碍不那么敏感。结果是通过认知测试在慢性苯丙胺、甲基苯丙胺或日常约束压力后评估视觉(物体识别)和空间记忆(物体放置和放射状手臂迷宫)的雄性和雌性大鼠的结果。在长期应激或安非他明的作用下，男性在这些任务中受到损害，而女性则不受影响，受影响较小，或在表现上有所提高。这些观察表明，两性之间循环性腺激素水平的差异可能有助于两性的不同敏感性，并为女性提供内源性神经保护。令人惊讶的是，摘除卵巢的女性在接受了损害男性的压力养生法(每天21天的束缚)后，仍然没有受到损害。这些数据与有关雌激素神经保护作用的神经化学数据一起表明，雌激素的神经保护作用可能是性分化(组织效应)和成年期激素作用(激活效应)的结果。这些考虑因素和长期使用雌激素可能产生的不良/不良影响将与使用选择性雌激素受体调节剂治疗男性和女性慢性疾病有关。总之，尽管在解剖学和神经化学研究中已经提出了雌激素对神经保护的令人信服的证据，但很明显，在功能/行为方面还需要进一步的研究。
Evidence that estrogen protects neurons against toxic/ ischemic insults or degenerative/aging processes is evident in a variety of in vitro and in vivo systems. However, a critical remaining question is: Does the demonstrated morphologic and neurochemical protection by estrogen lead to a preservation of brain function or an enhanced ability to recover? To date, little basic research is available on this issue. Cognition is a critical function that might provide a sensitive way to examine this question. As a first step, we present results showing that two chronic environmental insults, psychoactive drugs and stress, produce gender-specific responses in cognitive abilities. Specifically, females appear less sensitive than males to cognitive impairments following chronic exposure to these factors. Results are presented in male and female rats utilizing cognitive tests that assess visual (object recognition) and spatial memory (object placement and radial arm maze) following chronic amphetamine, methamphetamine, or daily restraint stress. Following regimes of chronic stress or amphetamine, males were impaired on these tasks while females were either unaffected, less affected, or enhanced in performance. These observations suggest that differences in circulating gonadal hormone levels between the sexes may contribute to the differential sensitivity of the sexes and provide endogenous neuroprotection for females. Surprisingly, ovariectomized females were still not impaired following a stress regimen that impaired males (21 d of daily restraint). These data taken together with neurochemical data on estrogen neuroprotective effects indicate that it is possible that neuroprotection by estrogen may result from hormone action both during sexual differentiation (organizational effect) and in adulthood (activational effect). These considerations and possible unwanted/untoward effects of chronic estrogen use are discussed in relation to the use of selective estrogen receptor modulators for chronic treatment of both males and females. In conclusion, although compelling evidence for neuroprotection by estrogen has been presented in anatomic and neurochemical studies, it is clear that the functional/ behavioral aspects need further investigation.