Remyelination alters the pattern of myelin in the cerebral cortex
- University of Pennsylvania, United States
- Johns Hopkins University School of Medicine, United States
- Massachusetts General Hospital, United States
- Baylor College of Medicine, United States
Abstract
Destruction of oligodendrocytes and myelin sheaths in cortical gray matter profoundly alters neural activity and is associated with cognitive disability in multiple sclerosis (MS). Myelin can be restored by regenerating oligodendrocytes from resident progenitors; however, it is not known whether regeneration restores the complex myelination patterns in cortical circuits. Here we performed time lapse in vivo two photon imaging in somatosensory cortex of adult mice to define the kinetics and specificity of myelin regeneration after acute oligodendrocyte ablation. These longitudinal studies revealed that the pattern of myelination in cortex changed dramatically after regeneration, as new oligodendrocytes were formed in different locations and new sheaths were often established along axon segments previously lacking myelin. Despite the dramatic increase in axonal territory available, oligodendrogenesis was persistently impaired in deeper cortical layers that experienced higher gliosis. Repeated reorganization of myelin patterns in MS may alter circuit function and contribute to cognitive decline.
Data availability
All data generated or analyzed in this study are included in the manuscript. Source code for analysis and figure generation are located at: https//github.com/clcall/Orthmann-Murphy_Call_etal_2020_Elife
Article and author information
Author details
Gian C Molina-Castro
Funding
Conrad N. Hilton Foundation
- Jennifer Orthmann-Murphy
National Multiple Sclerosis Society
- Jennifer Orthmann-Murphy
National Science Foundation (Graduate Research Fellowship)
- Cody L Call
National Science Foundation (Graduate Research Fellowship)
- Gian C Molina-Castro
National Institutes of Health (NS051509)
- Dwight E Bergles
National Institutes of Health (NS050274)
- Dwight E Bergles
National Institutes of Health (NS080153)
- Dwight E Bergles
Dr. Miriam and Sheldon G Adelson Medical Research Foundation
- Dwight E Bergles
National Multiple Sclerosis Society
- Peter A Calabresi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experimentation: This study was performed in accordance with the recommendations provided in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments and procedures were approved by the Johns Hopkins Institutional Care and Use Committee (protocols: MO17M268, MO17M338). All surgery was performed under isoflurane anesthesia and every effort was made to minimize suffering.
Copyright
© 2020, Orthmann-Murphy et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Remyelination alters the pattern of myelin in the cerebral cortex
eLife 9:e56621.
https://doi.org/10.7554/eLife.56621
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