Vitamin D protects dopaminergic neurons against neuroinflammation and oxidative stress in hemiparkinsonian rats

J Neuroinflammation. 2018 Aug 31;15(1):249. doi: 10.1186/s12974-018-1266-6.

Abstract

Background: The deficiency in 1α, 25-dihydroxyvitamin D3 (VD3) seems to increase the risk for neurodegenerative pathologies, including Parkinson's disease (PD). The majority of its actions are mediated by the transcription factor, VD3 receptor (VD3R).

Methods: The neuroprotective effects of VD3 were investigated on a PD model. Male Wistar rats were divided into the following groups: sham-operated (SO), 6-OHDA-lesioned (non-treated), and 6-OHDA-lesioned and treated with VD3 (7 days before the lesion, pre-treatment or for 14 days after the 6-OHDA striatal lesion, post-treatment). Afterwards, the animals were subjected to behavioral tests and euthanized for striatal neurochemical and immunohistochemical assays. The data were analyzed by ANOVA and the Tukey test and considered significant for p < 0.05.

Results: We showed that pre- or post-treatments with VD3 reversed behavioral changes and improved the decreased DA contents of the 6-OHDA group. In addition, VD3 reduced the oxidative stress, increased (TH and DAT), and reduced (TNF-alpha) immunostainings in the lesioned striata. While significant decreases in VD3R immunoreactivity were observed after the 6-OHDA lesion, these changes were blocked after VD3 pre- or post-treatments. We showed that VD3 offers neuroprotection, decreasing behavioral changes, DA depletion, and oxidative stress. In addition, it reverses partially or completely TH, DAT, TNF-alpha, and VD3R decreases of immunoreactivities in the non-treated 6-OHDA group.

Conclusions: Taken together, VD3 effects could result from its anti-inflammatory and antioxidant actions and from its actions on VD3R. These findings should stimulate translational research towards the VD3 potential for prevention or treatment of neurodegenerative diseases, as PD.

Keywords: Neuroinflammation; Oxidative stress; Parkinson’s disease and neurodegeneration; Vitamin D; Vitamin D receptors.

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopaminergic Neurons / drug effects*
  • Encephalitis / etiology*
  • Encephalitis / pathology*
  • Exploratory Behavior / drug effects
  • Lipid Peroxidation / drug effects
  • Male
  • Oxidative Stress / drug effects*
  • Oxidopamine / toxicity
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / complications*
  • Rats
  • Rats, Wistar
  • Stereotyped Behavior / drug effects
  • Swimming / physiology
  • Sympatholytics / toxicity
  • Tyrosine 3-Monooxygenase / metabolism
  • Vitamin D / pharmacology*

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Sympatholytics
  • Vitamin D
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Apomorphine
  • Dopamine