Takuma K, Matsuo A, Himeno Y, Hoshina Y, Ohno Y, Funatsu Y, Arai S, Kamei H, Mizoguchi H, Nagai T, Koike K, Inoue M, Yamada K
Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
Neuroscience. 2007 Apr 25;146(1):60-8. doi: 10.1016/j.neuroscience.2007.01.017. Epub 2007 Feb 22.
Several lines of evidence suggest that hormonal changes after menopause may play an important role in the incidence of cognitive dysfunction, and also in the development of Alzheimer's disease. In this study, we investigated the effect of estrogen on cognitive function in rats under different stress environment. Female rats were divided into four groups: two groups were ovariectomized (OVX) and two were sham-operated. One group each of OVX and sham rats was kept in a normal environment, and the other groups were assigned to a daily restraint stress (6 h/day) for 21 days from 2 months after the operation. Following the stress period, subjects were tested for performance in novel object recognition test and then used for morphological and neurochemical analyses. The OVX plus stress (OVX/stress) group showed a significant impairment of recognition of novel objects, compared with the other groups. The OVX/stress group also showed a marked decrease in the number of pyramidal cells of the CA3 region and levels of brain-derived neurotrophic factor mRNA in the hippocampus. We further examined the effect of estrogen against cognitive dysfunction and hippocampal changes of OVX/stress rats. Vehicle or 17beta-estradiol (E2) at 20 microg/day was s.c. administered to OVX/stress rats from 2 days before the stress period to the end of behavioral analysis through an implantable osmotic pump. Chronic E2 treatment decreased stress response and improved the cognitive and morphological impairments relative to vehicle group. These data have important implications for cognition enhancing effect of estrogen treatment in postmenopausal women.
多项证据表明，绝经后的激素变化可能在认知功能障碍的发生以及阿尔茨海默病的发展中起重要作用。在本研究中，我们调查了雌激素在不同应激环境下对大鼠认知功能的影响。将雌性大鼠分为四组：两组进行卵巢切除（OVX），两组进行假手术。OVX组和假手术组各有一组饲养在正常环境中，另一组在手术后2个月开始每天接受6小时的束缚应激，持续21天。应激期结束后，对实验对象进行新物体识别测试，并用于形态学和神经化学分析。与其他组相比，OVX加应激（OVX/应激）组在识别新物体方面表现出明显受损。OVX/应激组还显示CA3区锥体细胞数量和海马中脑源性神经营养因子mRNA水平显著降低。我们进一步研究了雌激素对OVX/应激大鼠认知功能障碍和海马变化的影响。从应激期前2天到行为分析结束，通过植入式渗透泵给OVX/应激大鼠皮下注射溶剂或每天20微克的17β-雌二醇（E2）。相对于溶剂组，慢性E2治疗降低了应激反应，改善了认知和形态学损伤。这些数据对绝经后妇女雌激素治疗的认知增强作用具有重要意义。
