PUBLICATION

Regeneration of myelin sheaths of normal length and thickness in the zebrafish CNS correlates with growth of axons in caliber

Authors
Karttunen, M.J., Czopka, T., Goedhart, M., Early, J.J., Lyons, D.A.
ID
ZDB-PUB-170526-7
Date
2017
Source
PLoS One   12: e0178058 (Journal)
Registered Authors
Czopka, Tim, Karttunen, Marja, Lyons, David A.
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Axons/physiology*
  • Axons/ultrastructure
  • Central Nervous System/physiology
  • Demyelinating Diseases/therapy
  • Disease Models, Animal
  • Microscopy, Electron, Transmission
  • Myelin Sheath/physiology*
  • Myelin Sheath/ultrastructure
  • Oligodendroglia/ultrastructure
  • Regeneration/physiology*
  • Zebrafish/physiology
PubMed
28542521 Full text @ PLoS One
Abstract
Demyelination is observed in numerous diseases of the central nervous system, including multiple sclerosis (MS). However, the endogenous regenerative process of remyelination can replace myelin lost in disease, and in various animal models. Unfortunately, the process of remyelination often fails, particularly with ageing. Even when remyelination occurs, it is characterised by the regeneration of myelin sheaths that are abnormally thin and short. This imperfect remyelination is likely to have implications for the restoration of normal circuit function and possibly the optimal metabolic support of axons. Here we describe a larval zebrafish model of demyelination and remyelination. We employ a drug-inducible cell ablation system with which we can consistently ablate 2/3rds of oligodendrocytes in the larval zebrafish spinal cord. This leads to a concomitant demyelination of 2/3rds of axons in the spinal cord, and an innate immune response over the same time period. We find restoration of the normal number of oligodendrocytes and robust remyelination approximately two weeks after induction of cell ablation, whereby myelinated axon number is restored to control levels. Remarkably, we find that myelin sheaths of normal length and thickness are regenerated during this time. Interestingly, we find that axons grow significantly in caliber during this period of remyelination. This suggests the possibility that the active growth of axons may stimulate the regeneration of myelin sheaths of normal dimensions.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
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Mapping