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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / psychology*
  • Animals
  • Cholecalciferol*
  • Cognitive Dysfunction / etiology*
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / psychology*
  • Dietary Supplements
  • Hippocampus / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Maze Learning / drug effects
  • Memory
  • Mice
  • Mice, Neurologic Mutants
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics*
  • Phosphorylation
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Vitamin D / therapeutic use
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / genetics
  • Vitamin D Deficiency / psychology*


  • Intercellular Signaling Peptides and Proteins
  • NR2B NMDA receptor
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • collapsin response mediator protein-2
  • Vitamin D
  • Cholecalciferol