Melatonin ameliorates cerebral ischemia-reperfusion injury in diabetic mice by enhancing autophagy via the SIRT1-BMAL1 pathway.
FASEB J
; 35(12): e22040, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34800293
ABSTRACT
Diabetic brains are more vulnerable to ischemia-reperfusion injury. Previous studies have proved that melatonin could protect against cerebral ischemia-reperfusion (CIR) injury in non-diabetic stroke models; however, its roles and the underlying mechanisms against CIR injury in diabetic mice remain unknown. Streptozotocin-induced diabetic mice and high-glucose-cultured HT22 cells were exposed to melatonin, with or without administration of the autophagy inhibitor 3-methyladenine (3-MA) and the specifically silent information regulator 1 (SIRT1) inhibitor EX527, and then subjected to CIR or oxygen-glucose deprivation/reperfusion operation. We found that diabetic mice showed aggravated brain damage, increased apoptosis and oxidative stress, and deficient autophagy following CIR compared with non-diabetic counterparts. Melatonin treatment exhibited improved histological damage, neurological outcomes, and cerebral infarct size. Intriguingly, melatonin markedly increased cell survival, anti-oxidative and anti-apoptosis effects, and significantly enhanced autophagy. However, these effects were largely attenuated by 3-MA or EX527. Additionally, our cellular experiments demonstrated that melatonin increased the SIRT1-BMAL1 pathway-related proteins' expression in a dose-dependent manner. In conclusion, these results indicate that melatonin treatment can protect against CIR-induced brain damage in diabetic mice, which may be achieved by the autophagy enhancement mediated by the SIRT1-BMAL1 pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Traumatismo por Reperfusão
/
Isquemia Encefálica
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Diabetes Mellitus Experimental
/
Sirtuína 1
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Fatores de Transcrição ARNTL
/
Melatonina
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China