Vitamin D Alleviates Cognitive Dysfunction by Activating the VDR/ERK1/2 Signaling Pathway in an Alzheimer’s Disease Mouse Model

Abstract

<b><i>Objective:</i></b> 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. <b><i>Material and Methods:</i></b> 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 (<i>n</i> = 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> This study provides new clues about the mechanism by which Vit D exerts neuroprotective effects in an AD mouse model.