Vitamin D confers protection to motoneurons and is a prognostic factor of amyotrophic lateral sclerosis

Neurobiol Aging. 2014 May;35(5):1198-205. doi: 10.1016/j.neurobiolaging.2013.11.005. Epub 2013 Nov 13.

Abstract

Amyotrophic lateral sclerosis (ALS) is an incurable paralytic disorder primarily typified by the selective and progressive degeneration of motoneurons in the brain and spinal cord. ALS causes muscle wasting and atrophy, resulting eventually in respiratory failure and death within 3-5 years of diagnosis. Vitamin D is a potent secosteroid hormone with diverse biological functions that include protection against neuronal damage. The detrimental consequences of vitamin D dietary deficiency have been documented in other neurodegenerative diseases. However, the protective effect of vitamin D on motoneuron and the influence of its levels on disease course remains elusive. Here we found that the biologically active form of vitamin D significantly potentiated the effect of neurotrophic factors and prevented motoneurons from a Fas-induced death, while electrophysiological properties of motoneurons were not affected. In ALS patients, we report that a severe vitamin D deficiency accelerates by 4 times the rate of decline and were associated with a marked shorter life expectancy. Our findings support a neuroprotective function of vitamin D on motoneurons and propose vitamin D as a reliable prognostic factor of ALS.

Keywords: Fas; Motoneurons; Neurotrophic factor; Prognostic factor; Vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / mortality
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Cell Survival / drug effects*
  • Cells, Cultured
  • Fas Ligand Protein / physiology
  • Female
  • Glial Cell Line-Derived Neurotrophic Factor / pharmacology
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Motor Neurons / drug effects*
  • Neurites / physiology
  • Neuroprotective Agents*
  • Survival Rate
  • Time Factors
  • Vitamin D / administration & dosage
  • Vitamin D / pharmacology*

Substances

  • Fas Ligand Protein
  • Glial Cell Line-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • Vitamin D