Cerebroprotective Role of N6-Methyladenosine Demethylase FTO (Fat Mass and Obesity-Associated Protein) After Experimental Stroke.
Stroke
; 54(1): 245-254, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36321453
ABSTRACT
BACKGROUND:
FTO (fat mass and obesity-associated protein) demethylates N6-methyladenosine (m6A), which is a critical epitranscriptomic regulator of neuronal function. We previously reported that ischemic stroke induces m6A hypermethylation with a simultaneous decrease in FTO expression in neurons. Currently, we evaluated the functional significance of restoring FTO with an adeno-associated virus 9, and thus reducing m6A methylation in poststroke brain damage.METHODS:
Adult male and female C57BL/6J mice were injected with FTO adeno-associated virus 9 (intracerebral) at 21 days prior to inducing transient middle cerebral artery occlusion. Poststroke brain damage (infarction, atrophy, and white matter integrity) and neurobehavioral deficits (motor function, cognition, depression, and anxiety-like behaviors) were evaluated between days 1 and 28 of reperfusion.RESULTS:
FTO overexpression significantly decreased the poststroke m6A hypermethylation. More importantly, exogenous FTO substantially decreased poststroke gray and white matter damage and improved motor function recovery, cognition, and depression-like behavior in both sexes.CONCLUSIONS:
These results demonstrate that FTO-dependent m6A demethylation minimizes long-term sequelae of stroke independent of sex.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acidente Vascular Cerebral
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article