Metformin treatment reduces inflammation, dysmyelination and disease severity in a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis.
Brain Res
; 1822: 148648, 2024 01 01.
Article
en En
| MEDLINE
| ID: mdl-37890574
ABSTRACT
Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation, death or damage of oligodendrocytes, and axonal degeneration. Current MS treatments are non-curative, associated with undesired side-effects, and expensive, highlighting the need for expanded therapeutic options for patients. There is great interest in developing interventions using drugs or therapeutics to reduce symptom onset and protect pre-existing myelin. Metformin is a well-tolerated drug used to treat Type 2 diabetes that has pleiotropic effects in the central nervous system (CNS), including reducing inflammation, enhancing oligodendrogenesis, increasing the survival/proliferation of neural stem cells (NSCs), and increasing myelination. Here, we investigated whether metformin administration could improve functional outcomes, modulate oligodendrocyte precursor cells (OPCs), and reduce inflammation in a well-established mouse model of MS- experimental autoimmune encephalomyelitis (EAE). Male and female mice received metformin treatment at the time of EAE induction ("acute") or upon presentation of disease symptoms ("delayed"). We found that acute metformin treatment improved functional outcomes, concomitant with reduced microglia numbers and decreased dysmyelination. Conversely, delayed metformin treatment did not improve functional outcomes. Our findings reveal that metformin administration can improve EAE outcomes when administered before symptom onset in both sexes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
/
Encefalomielitis Autoinmune Experimental
/
Metformina
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Esclerosis Múltiple
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Brain Res
Año:
2024
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Países Bajos