Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery
Autor: | Ari J. Green, J. Josh Lawrence, Lan Xiao, Klaus Lehmann-Horn, Daniel S. Lorrain, Jonah R. Chan, Feng Mei, Jürgen Wess, Karin J. Stebbins, Cory Teuscher, Sharon A. Sagan, H-Christian von Büdingen, Scott S. Zamvil, Kara Pekarek, Stephen P.J. Fancy, Yun-An A Shen, Kelsey Rankin |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Mouse QH301-705.5 Science Axonal loss oligodendrocytes Inflammation Degeneration (medical) General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Myelin 0302 clinical medicine medicine Biology (General) Remyelination General Immunology and Microbiology business.industry General Neuroscience Experimental autoimmune encephalomyelitis Oligodendrocyte differentiation myelination General Medicine Functional recovery medicine.disease 030104 developmental biology medicine.anatomical_structure nervous system Immunology Rat Medicine demyelination medicine.symptom business Neuroscience 030217 neurology & neurosurgery Research Article |
Zdroj: | eLife, Vol 5 (2016) eLife |
ISSN: | 2050-084X |
Popis: | 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. DOI: http://dx.doi.org/10.7554/eLife.18246.001 |
Databáze: | OpenAIRE |
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