Beta amyloid suppresses the expression of the vitamin d receptor gene and induces the expression of the vitamin d catabolic enzyme gene in hippocampal neurons

Dement Geriatr Cogn Disord. 2013;36(1-2):76-86. doi: 10.1159/000350319. Epub 2013 Jun 7.

Abstract

Background/aims: The beta amyloid aggregations present in Alzheimer's disease affect neurons through various toxic alterations. The aim of this study was to determine the expression of the vitamin D receptor (VDR), 25-hydroxyvitamin D3 24-hydroxylase (an accelerator of vitamin D catabolism), and the L-type voltage-sensitive calcium channel A1C (LVSCC-A1C) in hippocampal neurons in response to beta amyloid and vitamin D treatments to test the protective effects of vitamin D and the probable effects of beta amyloid on vitamin D catabolism.

Methods: The expression of the VDR, 24-hydroxylase (24OHase) and LVSCC-A1C mRNAs were studied using quantitative real-time polymerase chain reaction, and the cytotoxicity levels were determined by an ELISA in primary hippocampal neuron cultures prepared from Sprague-Dawley rat embryos.

Results: Our results demonstrated that beta amyloid suppressed the expression of VDR mRNA and induced the expression of 24OHase and LVSCC-A1C mRNAs.

Conclusion: Beta amyloid may disrupt the vitamin D-VDR pathway and cause defective utilization of vitamin D by suppressing the level of the VDR and elevating the level of 24OHase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / biosynthesis*
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Calcitriol / metabolism
  • Calcium Channels, L-Type / biosynthesis
  • Calcium Channels, L-Type / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Gene Expression / drug effects
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Hippocampus / metabolism*
  • L-Lactate Dehydrogenase / metabolism
  • Neurons / drug effects
  • Neurons / enzymology
  • Neurons / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptors, Calcitriol / biosynthesis*
  • Receptors, Calcitriol / genetics*
  • Vitamin D / metabolism

Substances

  • Amyloid beta-Peptides
  • Calcium Channels, L-Type
  • RNA, Messenger
  • Receptors, Calcitriol
  • Vitamin D
  • L-Lactate Dehydrogenase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcitriol