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

Ludmila A R Lima,Geanne M Andrade,Roberta O Costa,Francisco Arnaldo V Lima,Iana B F Calou,Glauce S B Viana,Kelly Rose T Neves,Maria Janice P Lopes

doi:10.1186/s12974-018-1266-6

Ludmila A R Lima, Geanne M Andrade + Show 6 more

Open Access

https://doi.org/10.1186/s12974-018-1266-6

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Abstract

BackgroundThe 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).MethodsThe 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.ResultsWe 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.ConclusionsTaken 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.

Highlights

The deficiency in 1α, 25-dihydroxyvitamin D3 (VD3) seems to increase the risk for neurodegenerative pathologies, including Parkinson’s disease (PD)
A decline in VD3 levels will lead to a dysregulation in Reactive oxygen species (ROS) and Ca2+ signaling pathways and, in some neurodegenerative pathologies as Alzheimer’s disease (AD), it might initiate beta-amyloid formation which progresses to neuronal death and dementia [6, 7]
Behavioral tests In the open field test, the non-treated 6-OHDA group showed a reduced motor activity with a 46% decrease in the number of crossings/5 min

Summary

Introduction

The deficiency in 1α, 25-dihydroxyvitamin D3 (VD3) seems to increase the risk for neurodegenerative pathologies, including Parkinson’s disease (PD). There is a critical need for new drugs and drug targets focusing on the protection of dopaminergic neurons from degeneration [3]. A decline in VD3 levels will lead to a dysregulation in ROS and Ca2+ signaling pathways and, in some neurodegenerative pathologies as Alzheimer’s disease (AD), it might initiate beta-amyloid formation which progresses to neuronal death and dementia [6, 7]. Some clinical studies point out to the insufficient levels of vitamin D in patients with PD, as well as the relationship between this degree of deficiency and the severity of the disease [8,9,10]

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