A Novel Perspective for Alzheimer's Disease: Vitamin D Receptor Suppression by amyloid-β and Preventing the amyloid-β Induced Alterations by Vitamin D in Cortical Neurons

J Alzheimers Dis. 2011;23(2):207-19. doi: 10.3233/JAD-2010-101377.

Abstract

Amyloid-β (Aβ) is the core component of amyloid plaques of Alzheimer's disease (AD). The effects of Aβ include damage to neuronal plasma membrane, disruption of Ca(2+) homeostasis, and alterations of neurotrophic factor levels. The aim of this study was to determine the effects of Aβ treatment on vitamin D receptor (VDR), L-type voltage sensitive calcium channels A1C (LVSCC A1C), NGF, and observing the effects of vitamin D treatment on Aβ induced alterations in primary cortical neurons. As to the latter, we aimed to test the suggested neuroprotective role of vitamin D as a neglected neurosteroid. The expressions of VDR and LVSCC A1C were studied with qRT-PCR and Western blotting. NGF and cytotoxicity levels were determined by ELISA. Apoptotic cell death was investigated with caspase-3 protein expression by Western blotting. Our results showed that the Aβ triggers neurodegeneration not only by inducing LVSCC A1C expression and NGF levels and but also by dramatically suppressing VDR expression. Administration of vitamin D to this model protected neurons by preventing cytotoxicity and apoptosis, and also by downregulating LVSCC A1C and upregulating VDR. Additionally, vitamin D brought NGF expression to a state of equilibrium and did not show its apoptosis inducing effects. Consequently, prevention of Aβ toxicity which was one of the major component of AD type pathology by vitamin D treatment and understanding how Aβ effects vitamin D related pathways, might open up new frontiers in clarifying molecular mechanisms of neurodegeneration and provide basis for novel perspectives in both preventing and treating AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / pharmacology*
  • Analysis of Variance
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Culture Techniques
  • Cells, Cultured
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Calcitriol / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vitamin D / metabolism*
  • Vitamin D / pharmacology

Substances

  • Amyloid beta-Peptides
  • Receptors, Calcitriol
  • Vitamin D
  • Caspase 3