Suppression of murine experimental autoimmune encephalomyelitis development by 1,25-dihydroxyvitamin D3 with autophagy modulation

Chao Zhen; Xuedan Feng; Zhe Li; Yabo Wang; Bin Li; Lin Li; Moyuan Quan; Gaoning Wang; Li Guo

doi:10.1016/j.jneuroim.2015.01.012

Suppression of murine experimental autoimmune encephalomyelitis development by 1,25-dihydroxyvitamin D3 with autophagy modulation

J Neuroimmunol. 2015 Mar 15:280:1-7. doi: 10.1016/j.jneuroim.2015.01.012. Epub 2015 Jan 29.

Authors

Chao Zhen¹, Xuedan Feng¹, Zhe Li², Yabo Wang³, Bin Li⁴, Lin Li¹, Moyuan Quan¹, Gaoning Wang¹, Li Guo⁵

Affiliations

¹ Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000 Hebei, China.
² Department of Neurology, Hebei General Hospital, Shijiazhuang, 050051 Hebei, China.
³ Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051 Hebei, China.
⁴ Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000 Hebei, China; Key Laboratory of Hebei Neurology, Shijiazhuang, 050000 Hebei, China.
⁵ Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000 Hebei, China; Key Laboratory of Hebei Neurology, Shijiazhuang, 050000 Hebei, China. Electronic address: guoli12@163.com.

PMID: 25773147
DOI: 10.1016/j.jneuroim.2015.01.012

Abstract

Multiple sclerosis (MS) has been associated with a history of sub-optimal exposure to ultraviolet light, implicating vitamin D3 as a possible protective agent. We evaluated whether 1,25(OH)2D3 attenuates the progression of experimental autoimmune encephalomyelitis (EAE), and explored its potential mechanisms. EAE was induced in C57BL/6 mice via immunization with MOG35-55, and some mice received 1,25(OH)2D3. 1,25(OH)2D3 inhibited EAE progression. Additionally, 1,25(OH)2D3 reduced inflammation, demyelination, and neuron loss in the spinal cord. The protective effect of 1,25(OH)2D3 was associated with significantly elevated expression of Beclin1, increased Bcl-2/Bax ratio, and decreased LC3-II accumulation. Thus, 1,25(OH)2D3 may represent a promising new MS treatment.

Keywords: 1,25(OH)(2)D(3); Apoptosis; Autophagy; Experimental autoimmune encephalomyelitis; Multiple sclerosis.

MeSH terms

Animals
Apoptosis Regulatory Proteins / metabolism
Autophagy / drug effects*
Beclin-1
Calcitriol / pharmacology*
Calcitriol / therapeutic use*
Calcium Channel Agonists / pharmacology
Calcium Channel Agonists / therapeutic use
Cyclin D1 / metabolism
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental / chemically induced
Encephalomyelitis, Autoimmune, Experimental / complications
Encephalomyelitis, Autoimmune, Experimental / pathology
Encephalomyelitis, Autoimmune, Experimental / therapy*
Extremities / physiopathology
Female
Gene Expression Regulation / drug effects
Mice
Microtubule-Associated Proteins / metabolism
Myelin-Oligodendrocyte Glycoprotein / toxicity
Neurodegenerative Diseases / etiology
Neurodegenerative Diseases / prevention & control
Peptide Fragments / toxicity
Phosphopyruvate Hydratase / metabolism
Spinal Cord / pathology
bcl-2-Associated X Protein / metabolism

Substances

Apoptosis Regulatory Proteins
Beclin-1
Becn1 protein, mouse
Calcium Channel Agonists
Map1lc3b protein, mouse
Microtubule-Associated Proteins
Myelin-Oligodendrocyte Glycoprotein
Peptide Fragments
bcl-2-Associated X Protein
myelin oligodendrocyte glycoprotein (35-55)
Cyclin D1
Phosphopyruvate Hydratase
Calcitriol