Bao Zheng, Wang Xue, Li Yuhong, Feng Fumin
School of Public Health, North China University of Science and Technology, Tangshan, China.
Child Health Division, Tongzhou Maternal and Child Health Hospital of Beijing, Beijing, China.
Neuroimmunomodulation. 2020;27(4):178-185. doi: 10.1159/000510400. Epub 2021 Feb 18.
Vitamin D (Vit D), a steroid hormone, has been linked to cognitive impairment and dementia, such as Alz-heimer'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.
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.
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.
This study provides new clues about the mechanism by which Vit D exerts neuroprotective effects in an AD mouse model.
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,如阿尔茨海默病(AD)。1,25(OH)2D3是Vit D的生物活性形式,已被证明具有神经保护作用。该化合物正在作为AD模型中的一种新兴治疗方法进行评估。
本研究旨在探讨Vit D是否能通过调节VDR/ERK1/2信号通路来减轻AD大鼠模型中的认知障碍。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),40只年龄匹配的C57BL/6J小鼠分为对照组(CON)和Vit D + CON组(每组20只小鼠)。采用莫里斯水迷宫和物体识别测试来评估小鼠的学习和记忆功能。苏木精-伊红染色用于评估海马神经元的形态变化。蛋白质印迹法用于评估导致这些变化的蛋白质。
我们发现Vit D改善了学习和记忆能力以及海马神经元的形态缺陷。Vit D降低了caspase-3和Bax的基因表达,并增加了Bcl-2的表达。Vit D还增加了AD小鼠中VDR和p-ERK1蛋白的表达。
本研究为Vit D在AD小鼠模型中发挥神经保护作用的机制提供了新线索。