Metformin accelerates myelin recovery and ameliorates behavioral deficits in the animal model of multiple sclerosis via adjustment of AMPK/Nrf2/mTOR signaling and maintenance of endogenous oligodendrogenesis during brain self-repairing period.
AMP-Activated Protein Kinases
/ metabolism
Animals
Apoptosis
/ drug effects
Corpus Callosum
/ drug effects
Male
Metformin
/ pharmacology
Mice
Mice, Inbred C57BL
Molecular Docking Simulation
Motor Activity
/ drug effects
Multiple Sclerosis
/ drug therapy
Myelin Sheath
/ drug effects
NF-E2-Related Factor 2
/ metabolism
Oligodendroglia
/ drug effects
Oxidants
/ metabolism
Signal Transduction
/ drug effects
TOR Serine-Threonine Kinases
/ metabolism
AMPK
Cuprizone
Multiple sclerosis
Nrf2
mTOR
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
03
05
2019
accepted:
05
09
2019
revised:
25
08
2019
pubmed:
13
2
2020
medline:
13
4
2021
entrez:
13
2
2020
Statut:
ppublish
Résumé
Multiple sclerosis (MS) is a devastating autoimmune disorder characterized by oligodendrocytes (OLGs) loss and demyelination. In this study, we have examined the effects of metformin (MET) on the oligodendrogenesis, redox signaling, apoptosis, and glial responses during a self-repairing period (1-week) in the animal model of MS. For induction of demyelination, C57BL/6 J mice were fed a 0.2% cuprizone (CPZ) for 5 weeks. Thereafter, CPZ was removed for 1-week and molecular and behavioral changes were monitored in the presence or absence of MET (50 mg/kg body weight/day). MET remarkably increased the localization of precursor OLGs (NG2 Altogether, our study reveals that MET effectively induces lesion reduction and elevated molecular processes that support myelin recovery via direct activation of AMPK and indirect regulation of AMPK/Nrf2/mTOR pathway in OLGs. These findings facilitate the development of new therapeutic strategies based on AMPK activation for MS in the near future.
Sections du résumé
BACKGROUND
BACKGROUND
Multiple sclerosis (MS) is a devastating autoimmune disorder characterized by oligodendrocytes (OLGs) loss and demyelination. In this study, we have examined the effects of metformin (MET) on the oligodendrogenesis, redox signaling, apoptosis, and glial responses during a self-repairing period (1-week) in the animal model of MS.
METHODS
METHODS
For induction of demyelination, C57BL/6 J mice were fed a 0.2% cuprizone (CPZ) for 5 weeks. Thereafter, CPZ was removed for 1-week and molecular and behavioral changes were monitored in the presence or absence of MET (50 mg/kg body weight/day).
RESULTS
RESULTS
MET remarkably increased the localization of precursor OLGs (NG2
CONCLUSIONS
CONCLUSIONS
Altogether, our study reveals that MET effectively induces lesion reduction and elevated molecular processes that support myelin recovery via direct activation of AMPK and indirect regulation of AMPK/Nrf2/mTOR pathway in OLGs. These findings facilitate the development of new therapeutic strategies based on AMPK activation for MS in the near future.
Identifiants
pubmed: 32048246
doi: 10.1007/s43440-019-00019-8
pii: 10.1007/s43440-019-00019-8
doi:
Substances chimiques
NF-E2-Related Factor 2
0
Nfe2l2 protein, mouse
0
Oxidants
0
Metformin
9100L32L2N
mTOR protein, mouse
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
AMP-Activated Protein Kinases
EC 2.7.11.31
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
641-658Références
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