Markowska Alicja L, Savonenko Alena V
Neuromnemonics Laboratory, Department of Psychology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
J Neurosci. 2002 Dec 15;22(24):10985-95. doi: 10.1523/JNEUROSCI.22-24-10985.2002.
Recent studies suggest that some aspects of learning and memory may be altered by a midlife loss of estrogen, indicating a potential causal relationship between the deficiency of ovarian hormones and cognitive aging. In this study, the effects of estrogen withdrawal and replacement were tested in middle-aged Fischer-344 rats using different memory tasks. Estrogen withdrawal accelerated the rate of cognitive aging. A deficit first occurred 4 months after ovariectomy in working memory, which was tested in a delayed-nonmatching-to-position task, and progressed from long-delay to short-delay trials. Reference memory, which was tested in a place discrimination task and a split-stem T-maze, was not affected by aging or ovariectomy. The efficacy of estrogen in ameliorating the cognitive deficit in old rats depended on the type of treatment (acute vs chronic) and whether the aging-related decline in a particular cognitive process was aggravated by estrogen withdrawal. Chronic estrogen treatment (implants) was effective in improving working memory only when primed with repeated injections of estrogen, indicating that simulating the estrogen fluctuations of the estrous cycle may be more effective than the widely used mode of chronic pharmacological treatment. A challenge with scopolamine revealed that ovariectomy-induced cognitive deterioration coincided with a compromised cholinergic system. Importantly, the estrogen treatment that had restored effectively the cognitive abilities of old ovariectomized rats did not reduce their sensitivity to scopolamine. Taking into consideration that estrogen was highly effective against the amnestic action of scopolamine when tested in young-adult rats, these data emphasize that mechanisms of the protective effect of estrogen differ in young and old rats.
最近的研究表明，雌激素在中年期丧失可能会改变学习和记忆的某些方面，这表明卵巢激素缺乏与认知衰老之间可能存在因果关系。在本研究中，使用不同的记忆任务测试了中年Fischer-344大鼠中雌激素撤药和替代的影响。雌激素撤药加速了认知衰老的速度。在延迟位置匹配任务中测试的工作记忆在卵巢切除术后4个月首次出现缺陷，并从长延迟试验发展到短延迟试验。在位置辨别任务和分叉T迷宫中测试的参考记忆不受衰老或卵巢切除术的影响。雌激素改善老年大鼠认知缺陷的功效取决于治疗类型（急性与慢性）以及特定认知过程中与衰老相关的衰退是否因雌激素撤药而加剧。慢性雌激素治疗（植入物）仅在预先反复注射雌激素时才有效改善工作记忆，这表明模拟发情周期的雌激素波动可能比广泛使用的慢性药物治疗模式更有效。东莨菪碱激发试验表明，卵巢切除诱导的认知衰退与胆碱能系统受损同时发生。重要的是，有效恢复老年去卵巢大鼠认知能力的雌激素治疗并未降低它们对东莨菪碱的敏感性。考虑到在年轻成年大鼠中测试时雌激素对东莨菪碱的遗忘作用具有高度效力，这些数据强调雌激素的保护作用机制在年轻和老年大鼠中有所不同。
