Fat mass and obesity-associated protein regulates RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion.
Neuropeptides
; 105: 102428, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38583362
ABSTRACT
RNA methylation can epigenetically regulate learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of Vascular dementia (VD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus in models of VD. Through prediction and dual-luciferase reporters validation studies, we observed that miRNA-711 was upregulated after VD and could bind to the 3'-untranslated region of FTO mRNA and regulate its expression in vitro. Methylated RNA immunoprecipitation (MeRIP)-qPCR assay and functional study confirmed that Syn1 was an important target gene of FTO. This suggests that FTO is an important regulator of Syn1. FTO upregulation by inhibition of miR-711 in the hippocampus relieves synaptic association protein and synapse deterioration in vivo, whereas FTO downregulation by miR-711 agomir in the hippocampus leads to aggravate the synapse deterioration. FTO upregulation by inhibition of miR-711 relieves cognitive impairment of rats VD model, whereas FTO downregulation by miR-711 deteriorate cognitive impairment. Our findings suggest that FTO is a regulator of a mechanism underlying RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ratos Sprague-Dawley
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MicroRNAs
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Disfunção Cognitiva
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Dioxigenase FTO Dependente de alfa-Cetoglutarato
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Hipocampo
Limite:
Animals
Idioma:
En
Revista:
Neuropeptides
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China