17β-estradiol attenuates hippocampal neuronal loss and cognitive dysfunction induced by chronic restraint stress in ovariectomized rats
17β-estradiol attenuates hippocampal neuronal loss and cognitive dysfunction induced by chronic restraint stress in ovariectomized rats
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DOI：
10.1016/j.neuroscience.2007.01.017
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发表时间：
2007-04
期刊：
影响因子：
3.3
通讯作者：
K. Takuma;A. Matsuo;Y. Himeno;Y. Hoshina;Y. Ohno;Y. Funatsu;S. Arai;H. Kamei;H. Mizoguchi
中科院分区：
文献类型：
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作者：
K. Takuma;A. Matsuo;Y. Himeno;Y. Hoshina;Y. Ohno;Y. Funatsu;S. Arai;H. Kamei;H. Mizoguchi
多项证据表明，绝经后荷尔蒙的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发挥重要作用。本研究探讨了雌激素对不同应激环境下大鼠认知功能的影响。雌性大鼠被分为四组：两组进行卵巢切除（OVX），两组进行假手术。一组OVX大鼠和假大鼠均置于正常环境中，另一组从术后2个月起每天接受束缚应激（6小时/天），持续21天。压力期过后，受试者接受了新物体识别测试的表现，然后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）组对新物体的识别能力显着受损。 OVX/应激组还表现出CA3区锥体细胞数量和海马脑源性神经营养因子mRNA水平显着下降。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。皮下注射媒介物或 17β-雌二醇 (E2)，剂量为 20 μg/天。从应激期前 2 天到行为分析结束，通过植入式渗透泵对 OVX/应激大鼠进行给药。相对于赋形剂组，长期 E2 治疗可降低应激反应并改善认知和形态损伤。这些数据对于绝经后妇女雌激素治疗的认知增强作用具有重要意义。
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 17β-estradiol (E2) at 20 μg/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.