Remyelination by Resident Oligodendrocyte Precursor Cells in a Xenopus laevis Inducible Model of Demyelination

被引:9
|
作者
Sekizar, Sowmya [1 ,2 ,3 ]
Mannioui, Abdelkrim [1 ,2 ,3 ]
Azoyan, Loris [1 ,2 ,3 ]
Colin, Catherine [1 ,2 ,3 ]
Thomas, Jean-Leon [1 ,2 ,3 ,4 ,6 ]
Du Pasquier, David [5 ]
Mallat, Michel [1 ,2 ,3 ]
Zalc, Bernard [1 ,2 ,3 ,4 ]
机构
[1] Univ Paris 06, Sorbonne Univ, ICM GHU Pitie Salpetriere, UM 75, FR-75651 Paris 13, France
[2] Grp Hosp Pitie Salpetriere, Inserm U1127, F-75634 Paris, France
[3] Grp Hosp Pitie Salpetriere, CNRS UMR 7225, F-75634 Paris, France
[4] Grp Hosp Pitie Salpetriere, AP HP, F-75634 Paris, France
[5] Watchfrog, Evry, France
[6] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA
关键词
Myelin; Myelin repair; Microglia; Transgenic Xenopus model; Multiple sclerosis; Sox10; Isolectin B4; CENTRAL-NERVOUS-SYSTEM; CHICK OPTIC-NERVE; PROGENITOR CELLS; MULTIPLE-SCLEROSIS; WALLERIAN DEGENERATION; GLIAL-CELLS; MICROGLIA; CNS; MACROPHAGES; ORIGIN;
D O I
10.1159/000380817
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have generated a Xenopus laevis transgenic line, MBP-GFP-NTR, allowing conditional ablation of myelin-forming oligodendrocytes. In this transgenic line the transgene is driven by the proximal portion of the myelin basic protein regulatory sequence, specific to mature oligodendrocytes. The transgene protein is formed by the green fluorescent protein reporter fused to the Escherichia coli nitroreductase (NTR) selection enzyme. The NTR enzyme converts the innocuous prodrug metronidazole (MTZ) to a cytotoxin. Ablation of oligodendrocytes by MTZ treatment of the tadpole induced demyelination, and here we show that myelin debris are subsequently eliminated by microglial cells. After cessation of MTZ treatment, remyelination proceeded spontaneously. We questioned the origin of remyelinating cells. Our data suggest that Sox10+ oligodendrocyte precursor cells (OPCs), which are already present in the optic nerve prior to the experimentally induced demyelination, are responsible for remyelination, and this required only minimal (if any) cell division of OPCs. (C) 2015 S. Karger AG, Basel
引用
收藏
页码:232 / 242
页数:11
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