Format

Send to

Choose Destination
Elife. 2016 Sep 27;5. pii: e18246. doi: 10.7554/eLife.18246.

Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery.

Author information

1
Department of Neurology, University of California, San Francisco, San Francisco, United States.
2
Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, China.
3
Inception Sciences, San Diego, United States.
4
Department of Medicine, Immunobiology Program, University of Vermont, Burlington, United States.
5
Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United States.
6
Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, United States.
7
Department of Pediatrics, University of California, San Francisco, San Francisco, United States.

Abstract

Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises to restore lost function, it remains unclear whether remyelination will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss in the experimental autoimmune encephalomyelitis (EAE) mouse model and evidence for remyelination in this model is complicated by ongoing inflammation, degeneration and possible remyelination. Demonstrating the functional significance of remyelination necessitates selectively altering the timing of remyelination relative to inflammation and degeneration. We demonstrate accelerated remyelination after EAE induction by direct lineage analysis and hypothesize that newly formed myelin remains stable at the height of inflammation due in part to the absence of MOG expression in immature myelin. Oligodendroglial-specific genetic ablation of the M1 muscarinic receptor, a potent negative regulator of oligodendrocyte differentiation and myelination, results in accelerated remyelination, preventing axonal loss and improving functional recovery. Together our findings demonstrate that accelerated remyelination supports axonal integrity and neuronal function after inflammatory demyelination.

KEYWORDS:

demyelination; mouse; myelination; neuroscience; oligodendrocytes; rat

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center