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Neuropharmacology. 2020 Mar 1;164:107910. doi: 10.1016/j.neuropharm.2019.107910. Epub 2019 Dec 12.

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

Author information

1
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
2
Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan; Clinical Competency Center, Chi Mei Medical Center, Tainan, Taiwan.
3
Department of Neurosurgery, Chi-Mei Medical Center, Tainan, Taiwan; Center for General Education, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
4
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: yahsin@mail.ncku.edu.tw.

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.

KEYWORDS:

3xTg-AD mice; Alzheimer's disease; CRMP2; Memory impairment; Vitamin D

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