卵巢切除对APP/PS1小鼠认知功能和海马雌激素受体表达的影响
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1.上海中医药大学附属龙华医院;2.上海中医药大学

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国家自然科学基金资助项目(82174427)


The effect of ovariectomy on cognitive function and hippocampal estrogen receptor expression in APP/PS1 mice
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1.Longhua Hospital of Shanghai University of Traditional Chinese Medicine;2.Shanghai University of Traditional Chinese Medicine

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    摘要:

    摘要:目的:本研究旨在观察阿尔茨海默病(Alzheimer’s disease, AD)动物模型APP/PS1雌性小鼠卵巢切除(ovariectomized,ovx)术后海马组织中Aβ沉积和雌激素受体水平在不同月龄的变化规律。方法:将3月龄APP/PS1雌性小鼠分3组,每组20只,每组10只采用经腹手术切除双侧卵巢作为模型组,10只对照组(sham组)手术时仅摘除相应部位的等体积脂肪作为对照组(sham组),分别饲养3个月、4个月、5个月作为6月龄组、7月龄组、8月龄组,通过Morris水迷宫评价不同月龄APP/PS1小鼠认知功能,透射电镜观察两组小鼠海马CA1区细胞内细胞器形态变化,免疫荧光染色检测两组小鼠海马CA1区Aβ沉积,ELISA检测两组小鼠血清雌激素、ROS、SOD、MDA水平和含量,western blot测定ERα和Erβ表达水平。结果:随着月龄的不断增加,水迷宫测试中ovx组小鼠逃避潜伏期逐渐延长,海马CA1区Aβ沉积增加、海马神经元线粒体肿胀增加,胞浆内见大量脂褐素及淀粉样沉积;血清雌二醇水平、SOD活力下降,ROS水平、MDA含量水平增加,海马组织ERα和ERβ表达降低。结论:小鼠卵巢切除术后可能会加剧海马Aβ沉积,其认知功能降低呈现年龄依赖性。

    Abstract:

    Abstract: Objective: The present study aims to observe the changes in Aβ deposition and estrogen receptor levels in the hippocampal tissue of female APP/PS1 mice with Alzheimer's disease (AD) after ovariectomy (ovx) at different ages. Method: 3-month-old APP/PS1 female mice were divided into 3 groups, with 20 mice in each group. 10 mice in each group were treated with bilateral ovarian resection via abdominal surgery as the model group. 10 mice in the control group (sham group) were treated with only equivalent volume fat removed from the corresponding area during surgery as the control group (sham group). Feed APP/PS1 mice at different ages for 3 months, 4 months, and 5 months as the 6-month, 7-month, and 8-month age groups. Evaluate the cognitive function of APP/PS1 mice at different ages using Morris water maze. Observe the morphological changes of intracellular organelles in the CA1 area of the hippocampus of the two groups of mice using transmission electron microscopy. Immunofluorescence staining is used to detect the deposition of Aβ in the CA1 area of the hippocampus of the two groups of mice. ELISA is used to detect the levels and contents of serum estrogen, ROS, SOD, and MDA, and Western blot is used to determine the expression levels of ERα and ERβ. Result: As the age increased, the escape latency of the ovx group mice in the water maze test gradually prolonged, the deposition of Aβ in the hippocampal CA1 area increased, the mitochondrial swelling of hippocampal neurons increased, and a large amount of lipofuscin and amyloid deposition were observed in the cytoplasm. The serum estradiol level and SOD activity decrease, while the ROS level and MDA content increase. The expression of ERα and ERβ in hippocampal tissue decreases. Conclusion: Ovariectomy in mice with low estrogen status may exacerbate hippocampal Aβ deposition and age-dependent cognitive decline.

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  • 收稿日期:2024-04-16
  • 最后修改日期:2024-07-09
  • 录用日期:2024-07-11
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