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Age and axon-specific forms of cortical remyelination by divergent populations of NG2-glia

Timothy W. Chapman, Genaro E. Olveda, Elizabeth Pereira, View ORCID ProfileRobert A. Hill
doi: https://doi.org/10.1101/2020.12.09.414755
Timothy W. Chapman
1Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA
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Genaro E. Olveda
1Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA
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Elizabeth Pereira
1Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA
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Robert A. Hill
1Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA
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  • ORCID record for Robert A. Hill
  • For correspondence: robert.hill@dartmouth.edu
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ABSTRACT

Myelin is critical for neural circuit function and its destruction is widespread in neurodegenerative disease and aging. In these conditions, homeostatic repair mechanisms initiate oligodendrocyte replacement by resident progenitor cells called NG2-glia. To investigate the cellular dynamics of this repair we developed a novel demyelination model by combining intravital myelin imaging with a targeted single-cell ablation technique called 2Phatal. Oligodendrocyte 2Phatal activated a stereotyped degeneration cascade which triggered remyelination by local NG2-glia. Remyelination efficiency was dependent on initial myelin patterning and dynamic imaging revealed rapid repair mechanisms resulting in near-seamless transitions between myelin loss and repair. A subset of morphologically complex NG2-glia executed this remyelination, pointing towards unrecognized functional diversity within this population. Age-related demyelination mirrored the degenerative cascade observed with 2Phatal, while remyelination in aging was defective due to failed oligodendrogenesis. Thus, oligodendrocyte 2Phatal revealed cellular diversity within the oligodendrocyte lineage and uncovered novel forms of rapid remyelination.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 10, 2020.
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Age and axon-specific forms of cortical remyelination by divergent populations of NG2-glia
Timothy W. Chapman, Genaro E. Olveda, Elizabeth Pereira, Robert A. Hill
bioRxiv 2020.12.09.414755; doi: https://doi.org/10.1101/2020.12.09.414755
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Age and axon-specific forms of cortical remyelination by divergent populations of NG2-glia
Timothy W. Chapman, Genaro E. Olveda, Elizabeth Pereira, Robert A. Hill
bioRxiv 2020.12.09.414755; doi: https://doi.org/10.1101/2020.12.09.414755

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