Human IPSC-Derived Model to Study Myelin Disruption.

Détails

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Etat: Public
Version: de l'auteur⸱e
Licence: CC BY 4.0
ID Serval
serval:BIB_45BEDBE1924C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Human IPSC-Derived Model to Study Myelin Disruption.
Périodique
International journal of molecular sciences
Auteur⸱e⸱s
Chesnut M., Paschoud H., Repond C., Smirnova L., Hartung T., Zurich M.G., Hogberg H.T., Pamies D.
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Statut éditorial
Publié
Date de publication
31/08/2021
Peer-reviewed
Oui
Volume
22
Numéro
17
Pages
9473
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Myelin is of vital importance to the central nervous system and its disruption is related to a large number of both neurodevelopmental and neurodegenerative diseases. The differences observed between human and rodent oligodendrocytes make animals inadequate for modeling these diseases. Although developing human in vitro models for oligodendrocytes and myelinated axons has been a great challenge, 3D cell cultures derived from iPSC are now available and able to partially reproduce the myelination process. We have previously developed a human iPSC-derived 3D brain organoid model (also called BrainSpheres) that contains a high percentage of myelinated axons and is highly reproducible. Here, we have further refined this technology by applying multiple readouts to study myelination disruption. Myelin was assessed by quantifying immunostaining/confocal microscopy of co-localized myelin basic protein (MBP) with neurofilament proteins as well as proteolipid protein 1 (PLP1). Levels of PLP1 were also assessed by Western blot. We identified compounds capable of inducing developmental neurotoxicity by disrupting myelin in a systematic review to evaluate the relevance of our BrainSphere model for the study of the myelination/demyelination processes. Results demonstrated that the positive reference compound (cuprizone) and two of the three potential myelin disruptors tested (Bisphenol A, Tris(1,3-dichloro-2-propyl) phosphate, but not methyl mercury) decreased myelination, while ibuprofen (negative control) had no effect. Here, we define a methodology that allows quantification of myelin disruption and provides reference compounds for chemical-induced myelin disruption.
Mots-clé
Axons/metabolism, Brain/metabolism, Cell Culture Techniques/methods, Central Nervous System/metabolism, Humans, Induced Pluripotent Stem Cells/metabolism, Models, Biological, Myelin Basic Protein/analysis, Myelin Basic Protein/metabolism, Myelin Proteolipid Protein/analysis, Myelin Proteolipid Protein/metabolism, Myelin Sheath/metabolism, Myelin Sheath/physiology, Nerve Fibers, Myelinated/metabolism, Nerve Fibers, Myelinated/pathology, Neurotoxicity Syndromes/metabolism, Oligodendroglia/metabolism, Oligodendroglia/pathology, Organoids/metabolism, developmental diseases, developmental neurotoxicity, myelin, neurotoxicity, oligodendrocytes, organoid, organotypic
Pubmed
Web of science
Open Access
Oui
Création de la notice
21/09/2021 13:01
Dernière modification de la notice
25/02/2022 6:36
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