Chronic vitamin D3 supplementation alleviates cognition impairment via inhibition of oxidative stress regulated by PI3K/AKT/Nrf2 in APP/PS1 transgenic mice.

Abstract

Oxidative stress plays essential role in the pathogenesis of Alzheimer's disease, and vitamin D3 (VD3) is a nutrient with neuroprotective and antioxidant activities. The present study aimed to confirm the neuroprotective effect and the ameliorative effect of cortical oxidative stress of VD3 in APP/PS1 transgenic mice. APP/PS1 mice were treated with VD3 for 20 weeks. After treatment, Morris Water Maze test was used to evaluate cognitive level. Western blotting was used to determine APP, p-tau, tau and PI3K/AKT/Nrf2 pathway-related protein expression levels. Immunohistochemical staining was performed to determine the levels of β amyloid peptide (Aβ) deposition. Enzyme linked immunosorbent assay was used to determine the 25(OH)D3 levels and oxidative stress status. Our results showed that treatment with VD3 ameliorated behavioral deficits of APP/PS1 mice. In addition, the administration of VD3 significantly increased the cortical 25(OH)D3 levels, while reducing the levels of cortical Aβ deposition and decreasing the expression levels of cortical APP, tau and p-tau in APP/PS1 mice. Moreover, VD3 protected the cortex against oxidative stress by enhancing the levels of superoxide dismutase, glutathione and total antioxidant capacity, and downregulating the malondialdehyde levels. Furthermore, VD3 clearly activated the PI3K/AKT/Nrf2 pathway, thereby elevating the expression levels of HO1 and NQO1. We concluded that VD3 improved cognitive function and cortical Alzheimer-like pathology of APP/PS1 mice, which may be related to the inhibition of oxidative stress via activation the PI3K/AKT/Nrf2 pathway.

• Authors: Jisong Lin, Zhuoya Niu, Yuan Xue, Jiaojiao Gao, Mimi Zhang, Mengxin Li, Yangyang Peng, Shenshen Zhang, Wenjie Li, Qian Zhang, Xing Li
• Journal: Neuroscience letters (Neurosci Lett) Vol. 783 Pg. 136725 (07 13 2022) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 35697158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Antioxidants
• NF-E2-Related Factor 2
• Presenilin-1
• Cholecalciferol
• Proto-Oncogene Proteins c-akt

Topics

• Alzheimer Disease (drug therapy, metabolism)
• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor (genetics, metabolism)
• Animals
• Antioxidants (metabolism, pharmacology)
• Cholecalciferol (pharmacology, therapeutic use)
• Cognition
• Dietary Supplements
• Disease Models, Animal
• Mice
• Mice, Transgenic
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress
• Phosphatidylinositol 3-Kinases (metabolism)
• Presenilin-1 (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)