Relative D3 vitamin deficiency and consequent cognitive impairment in an animal model of Alzheimer's disease: Potential involvement of collapsin response mediator protein-2. (1st March 2020)

• Record Type: Journal Article
• Authors: Lin, Fang-Yu; Lin, Yu-Fen; Lin, Yung-Shuen; Yang, Chun-Ming; Wang, Che-Chuan; Hsiao, Ya-Hsin
• Is Part Of: Neuropharmacology. Volume 164(2020)
• Publication Date: 2020-03-01
• Subjects: CRMP2 -- Vitamin D -- Alzheimer's disease -- 3xTg-AD mice -- Memory impairment; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.107910
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Alzheimer's disease (AD) starts with memory impairments that can be observed before the appearance of significant neuropathology; thus, identifying mechanisms to stop AD progression is an urgent priority. Epidemiological and clinical data show that the consequences of vitamin D deficiency are relevant to disease risk and can be observed in the progression of many diseases, especially AD, whereas higher serum levels of vitamin D are associated with better cognitive test performance. However, the potential therapeutic strategy and underlying mechanisms of vitamin D supplementation against AD still need to be further investigated. In the present study, we found that 3xTg-AD mice with vitamin D supplementation exhibited an increase in serum vitamin D concentrations and improved cognition. We measured serum vitamin D binding protein (VDBP) concentrations and found that serum VDBP levels were increased in 3xTg-AD mice compared to B6129S control mice, but there was no significant difference between control- and vitamin D-treated 3xTg-AD groups. The vitamin D-mediated memory improvement may be accompanied by the suppression of increased hippocampal collapsin response mediator protein-2 (CRMP2) phosphorylation, and the restoration of CRMP2 phosphorylation by okadaic acid (OA) could abolish the beneficial effects of vitamin D. In addition, we found that CRMP2 was associated with NR2B and PSD-95 in 3xTg-AD mice with vitamin D supplementation. This CRMP2-NR2B interaction could be disrupted by a TAT-CBD3 peptide or OA, leading to attenuated memory protection in vitamin D-treated 3xTg-AD mice. Therefore, CRMP2 may be involved in vitamin D-mediated memory improvement in AD. Graphical abstract: Image 1 Highlights: Vitamin D improved cognitive decline in 3xTg-AD mice. Vitamin D eliminated the pCRMP2 increase in 3xTg-AD mice. Restoration of pCRMP2 expression abolished the vitamin D-mediated memory improvement. Improved memory in vitamin D-treated 3xTg-AD mice was mediated by CRMP2-NR2B association.