Structural adaption of axons during de- and remyelination in the Cuprizone mouse model.
Animals
Axons
/ metabolism
Cuprizone
/ pharmacology
Demyelinating Diseases
/ metabolism
Disease Models, Animal
Mice
Mice, Inbred C57BL
Mice, Transgenic
Multiple Sclerosis
/ metabolism
Myelin Sheath
/ metabolism
NAV1.6 Voltage-Gated Sodium Channel
/ physiology
Neurons
/ pathology
Oligodendroglia
/ pathology
Ranvier's Nodes
Remyelination
/ physiology
Sodium Channels
/ metabolism
VGlut1-positive vesicles
nodes of Ranvier
oligodendrocyte precursor cells
remyelination
sodium channels
ultrastructure of axons
Journal
Brain pathology (Zurich, Switzerland)
ISSN: 1750-3639
Titre abrégé: Brain Pathol
Pays: Switzerland
ID NLM: 9216781
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
30
01
2019
accepted:
14
05
2019
pubmed:
21
5
2019
medline:
10
3
2020
entrez:
21
5
2019
Statut:
ppublish
Résumé
Multiple Sclerosis is an autoimmune disorder causing neurodegeneration mostly in young adults. Thereby, myelin is lost in the inflammatory lesions leaving unmyelinated axons at a high risk to degenerate. Oligodendrocyte precursor cells maintain their regenerative capacity into adulthood and are able to remyelinate axons if they are properly activated and differentiate. Neuronal activity influences the success of myelination indicating a close interplay between neurons and oligodendroglia. The myelination profile determines the distribution of voltage-gated ion channels along the axon. Here, we analyze the distribution of the sodium channel subunit Nav1.6 and the ultrastructure of axons after cuprizone-induced demyelination in transgenic mice expressing GFP in oligodendroglial cells. Using this mouse model, we found an increased number of GFP-expressing oligodendroglial cells compared to untreated mice. Analyzing the axons, we found an increase in the number of nodes of Ranvier in mice that had received cuprizone. Furthermore, we found an enhanced portion of unmyelinated axons showing vesicles in the cytoplasm. These vesicles were labeled with VGlut1, indicating that they are involved in axonal signaling. Our results highlight the flexibility of axons towards changes in the glial compartment and depict the structural changes they undergo upon myelin removal. These findings might be considered if searching for new neuroprotective therapies that aim at blocking neuronal activity in order to avoid interfering with the process of remyelination.
Identifiants
pubmed: 31106489
doi: 10.1111/bpa.12748
pmc: PMC8028656
doi:
Substances chimiques
NAV1.6 Voltage-Gated Sodium Channel
0
Scn8a protein, mouse
0
Sodium Channels
0
Cuprizone
5N16U7E0AO
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
675-692Informations de copyright
© 2019 International Society of Neuropathology.
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