Assessing remyelination - metabolic labeling of myelin in an animal model of multiple sclerosis

J Neuroimmunol. 2016 Dec 15:301:7-11. doi: 10.1016/j.jneuroim.2016.10.015. Epub 2016 Nov 1.

Abstract

The lack of biomarkers is a major obstacle for investigating myelin repair. We used metabolic incorporation of the choline analog - propargyl-choline (P-Cho) to label and visualize newly synthesized myelin in the CNS of mice induced with experimental autoimmune encephalomyelitis (EAE). We further developed unbiased colocalization analysis to quantify P-Cho incorporation specifically into the myelin. Our findings indicate that P-Cho injection to mice recovering from EAE, either spontaneously or following glatiramer acetate treatment, results in significant elevation of its incorporation into the myelin, offering a novel strategy for assessing remyelination in animal models and the remyelination potential of candidate drugs.

Keywords: Experimental autoimmune encephalomyelitis (EAE); Glatiramer acetate (GA); In vivo metabolic labeling; Multiple sclerosis (MS); Quantitative colocalization analysis; Remyelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / metabolism
  • Animals
  • Cell Nucleolus / metabolism
  • Cell Nucleolus / pathology
  • Choline / analogs & derivatives
  • Choline / metabolism
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / diagnostic imaging
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Glatiramer Acetate / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Immunoelectron
  • Myelin Basic Protein / metabolism
  • Myelin Proteolipid Protein / toxicity
  • Myelin Sheath / metabolism*
  • Myelin Sheath / ultrastructure
  • Peptide Fragments / toxicity
  • Recovery of Function / drug effects
  • Recovery of Function / physiology*
  • Spinal Cord / pathology*
  • Spinal Cord / ultrastructure

Substances

  • Alkynes
  • Immunosuppressive Agents
  • Mbp protein, mouse
  • Myelin Basic Protein
  • Myelin Proteolipid Protein
  • Peptide Fragments
  • myelin proteolipid protein (139-151)
  • propargylcholine
  • Glatiramer Acetate
  • Choline