Assessing remyelination - metabolic labeling of myelin in an animal model of multiple sclerosis.
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.
Department of Immunology, Weizmann Institute of Science, Rehovot 761001, Israel. Electronic address: rina.aharoni@weizmann.ac.il.
Rina
R
Aharoni
Department of Immunology, Weizmann Institute of Science, Rehovot 761001, Israel.
Chava
C
Rosen
Department of Immunology, Weizmann Institute of Science, Rehovot 761001, Israel.
Elias
E
Shezen
Department of Immunology, Weizmann Institute of Science, Rehovot 761001, Israel.
Dekel D
DD
Bar-Lev
Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 761001, Israel.
Ofra
O
Golani
Department of Immunology, Weizmann Institute of Science, Rehovot 761001, Israel.
Yair
Y
Reisner
Department of Immunology, Weizmann Institute of Science, Rehovot 761001, Israel.
Michael
M
Sela
Department of Immunology, Weizmann Institute of Science, Rehovot 761001, Israel.
Ruth
R
Arnon
D000480:Alkynes / Q000378:metabolism; D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism / Q000473:pathology; D002794:Choline / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology*; D000068717:Glatiramer Acetate / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D016253:Microscopy, Immunoelectron; D004676:Myelin Basic Protein / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000633:toxicity; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000633:toxicity; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology* / Q000648:ultrastructure
D000480:Alkynes; D007166:Immunosuppressive Agents; C499047:Mbp protein, mouse; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); C000603143:propargylcholine; D000068717:Glatiramer Acetate; D002794:Choline
Experimental autoimmune encephalomyelitis (EAE); Glatiramer acetate (GA); In vivo metabolic labeling; Multiple sclerosis (MS); Quantitative colocalization analysis; Remyelination