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Vitamin D Alleviates Cognitive Dysfunction by Activating the VDR/ERK1/2 Signaling Pathway in an Alzheimer’s Disease Mouse Model
Neuroimmunomodulation ( IF 2.4 ) Pub Date : 2021-02-18 , DOI: 10.1159/000510400
Zheng Bao 1, 2 , Xue Wang 1 , Yuhong Li 1 , Fumin Feng 3, 4
Affiliation  

Objective: Vitamin D (Vit D), a steroid hormone, has been linked to cognitive impairment and dementia, such as Alz­heimer’s disease (AD). 1, 25(OH)2D3 is the biologically active form of Vit D, which has been shown to have neuroprotective effects. This compound is being evaluated as an emerging therapeutic treatment in models of AD. Material and Methods: The present study was designed to investigate whether Vit D could alleviate cognitive impairment in an AD rat model by regulating the VDR/ERK1/2 signaling pathway. Adult male APPswe/PS1ΔE9 rats (n = 40) were randomly divided into 2 groups: the AD group and the Vit D + AD group (20 mice per group), and 40 C57BL/6J age-matched mice were separated into the control (CON) group and the Vit D + CON group (20 mice per group). The Morris water maze and object recognition tests were used to evaluate learning and memory functions of the mice. Hematoxylin and eosin staining was used to evaluate morphological changes in hippocampal neurons. Western blotting was used to evaluate the proteins responsible for these changes. Results: We found that Vit D improved learning and memory abilities and morphological defects in hippocampal neurons. Vit D decreased the gene expression of caspase-3 and Bax and increased the expression of Bcl-2. Vit D also increased the protein expression of VDR and p-ERK1 protein in AD mice. Conclusion: This study provides new clues about the mechanism by which Vit D exerts neuroprotective effects in an AD mouse model.
Neuroimmunomodulation


中文翻译:

维生素 D 通过激活阿尔茨海默病小鼠模型中的 VDR/ERK1/2 信号通路缓解认知功能障碍

目的:维生素 D (Vit D) 是一种类固醇激素,与认知障碍和痴呆症有关,例如阿尔茨海默病 (AD)。1, 25(OH) 2 D 3是维生素 D 的生物活性形式,已被证明具有神经保护作用。该化合物正在被评估为 AD 模型中一种新兴的治疗方法。材料和方法:本研究旨在研究维生素 D 是否可以通过调节 VDR/ERK1/2 信号通路减轻 AD 大鼠模型的认知障碍。成年雄性 APPswe/PS1ΔE9 大鼠 ( n= 40) 随机分为 2 组:AD 组和 Vit D + AD 组(每组 20 只小鼠),将 40 只 C57BL/6J 年龄匹配的小鼠分为对照组(CON)和 Vit D + CON组(每组20只小鼠)。Morris水迷宫和物体识别测试用于评估小鼠的学习和记忆功能。苏木精和伊红染色用于评估海马神经元的形态变化。蛋白质印迹用于评估导致这些变化的蛋白质。结果:我们发现维生素 D 改善了海马神经元的学习和记忆能力以及形态缺陷。Vit D降低了caspase-3和Bax的基因表达,增加了Bcl-2的表达。Vit D 还增加了 AD 小鼠中 VDR 和 p-ERK1 蛋白的蛋白表达。结论:这项研究提供了关于 Vit D 在 AD 小鼠模型中发挥神经保护作用的机制的新线索。
神经免疫调节
更新日期:2021-02-18
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