Fat mass and obesity-associated protein regulates RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8103156 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-2785 (Electronic) Linking ISSN: 01434179 NLM ISO Abbreviation: Neuropeptides Subsets: MEDLINE
    • Publication Information:
      Publication: 2002- : Amsterdam : Elsevier
      Original Publication: Edinburgh ; New York : Churchill Livingstone, c1980-
    • Subject Terms:
      Alpha-Ketoglutarate-Dependent Dioxygenase FTO*/metabolism ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO*/genetics ; Cognitive Dysfunction*/metabolism ; Cognitive Dysfunction*/etiology ; Hippocampus*/metabolism ; MicroRNAs*/metabolism ; MicroRNAs*/genetics ; RNA Methylation*; Animals ; Male ; Rats ; Dementia, Vascular/metabolism ; Dementia, Vascular/genetics ; Disease Models, Animal ; Rats, Sprague-Dawley
    • 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.
      Competing Interests: Declaration of competing interest The authors declare no competing interests.
      (Copyright © 2024 Elsevier Ltd. All rights reserved.)
    • Contributed Indexing:
      Keywords: Cognitive impairment; FTO; Mir-711; Synaptic loss; Vascular dementia
    • Accession Number:
      EC 1.14.11.33 (Alpha-Ketoglutarate-Dependent Dioxygenase FTO)
      EC 1.14.11.33 (FTO protein, rat)
      0 (MicroRNAs)
    • Publication Date:
      Date Created: 20240407 Date Completed: 20240509 Latest Revision: 20240821
    • Publication Date:
      20240822
    • Accession Number:
      10.1016/j.npep.2024.102428
    • Accession Number:
      38583362