CZ-7, a new derivative of Claulansine F, promotes remyelination induced by cuprizone by enhancing myelin debris clearance.
CZ-7
Cuprizone
Demyelinating disease
Microglia
Myelin debris
Remyelination
Journal
Brain research bulletin
ISSN: 1873-2747
Titre abrégé: Brain Res Bull
Pays: United States
ID NLM: 7605818
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
18
11
2019
revised:
18
03
2020
accepted:
23
03
2020
pubmed:
15
4
2020
medline:
1
9
2021
entrez:
15
4
2020
Statut:
ppublish
Résumé
The mechanism of demyelinating diseases is controversial, while demyelination and remyeliantion disorder is the acknowledged etiology and therapeutic target. Untill now, there is no efficient therapy for these diseases. CZ-7, a new derivative of Claulansine F, which has been reported before, were investigated its pro-remyelination effect and its associated mechanism in cuprizone (CPZ)-induced demyelination model. In this study, male C57BL/6 mice were subjected to CPZ (300 mg/kg) through intragastric gavage and were orally administered CZ-7 (20 mg/kg) meanwhile. The results of weight monitoring and behavioral testing showed that CZ-7 can significantly improve behavior dysfunction in the demyelinating mice. Luxol-fast blue (LFB) staining, myelin basic protein (MBP) immunostaining, transmission electron microscopy (TEM) and QPCR results indicated the therapeutic effect of CZ-7 on CPZ mice model. Furthermore, degraded myelin basic protein (dMBP) immunofluorescent staining and oil red O staining showed that CZ-7 contributed to the clearance of degraded myelin debris. More microglia displayed phagocytic shape assembled in corpus callosum (CC) and there was an active process of phagocytosis in microglia after CZ-7 treatment. Immunofluorescent staining and QPCR analysis revealed the M2-polarized phenotype switch of microglia in the process of myelin debris removel, which demostrated the microenvironment improvement of CZ-7. Moreover, immunofluorescent staining of NG2 and O4 demonstated that more oligodendrocyte precursor cells (OPCs) existed in CC after CZ-7 treatment. In conclusion, our results demonstrated CZ-7 has a potential therapeutic effect for MS and other demyelinating diseases through enhancing myelin debris clearance to improve the microenvironment.
Identifiants
pubmed: 32289743
pii: S0361-9230(19)30927-X
doi: 10.1016/j.brainresbull.2020.03.017
pii:
doi:
Substances chimiques
Carbazoles
0
Chelating Agents
0
Myelin Proteins
0
claulansine F
0
Cuprizone
5N16U7E0AO
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
67-78Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no conflicts of interest.