Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Altered N6-methyladenosine Modification Patterns and Transcript Profiles Contributes to Cognitive Dysfunction in High-Fat Induced Diabetic Mice

Version 1 : Received: 15 December 2023 / Approved: 18 December 2023 / Online: 18 December 2023 (10:58:33 CET)

A peer-reviewed article of this Preprint also exists.

Cao, Z.; An, Y.; Lu, Y. Altered N6-Methyladenosine Modification Patterns and Transcript Profiles Contributes to Cognitive Dysfunction in High-Fat Induced Diabetic Mice. Int. J. Mol. Sci. 2024, 25, 1990. Cao, Z.; An, Y.; Lu, Y. Altered N6-Methyladenosine Modification Patterns and Transcript Profiles Contributes to Cognitive Dysfunction in High-Fat Induced Diabetic Mice. Int. J. Mol. Sci. 2024, 25, 1990.

Abstract

Abstract: Objectives: To establish the expression profile of N6-methyladenosine(m6A) modifications in the hippocampus of mice with diabetic cognitive impairment (DCI) and elucidate the potential regulatory mechanism. Methods: A DCI model was established by feeding a high-fat diet to C57BL/6J mice. m6A and RNA sequencing was conducted to profile the m6A-tagged transcripts in the hippocampus. Results: Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing analyses yielded differentially m6A-modified and expressed genes in the hippocampus of DCI mice, which were enriched in pathways involving synaptic transmission and axonal guidance. Mechanistic analyses revealed a remarkable change in m6A modification levels through alteration of the mRNA expression of m6A methyltransferases (METTL3 and METTL14) and demethylase (FTO) in the hippocampus of DCI mice. Conclusions: We identified a co-mediated specific RNA regulatory strategy that broadens the epigenetic regulatory mechanism of RNA-induced neurodegenerative disorders associated with metabolic and endocrine diseases.

Keywords

Diabetic cognitive impairment; High-fat feeding; m6A methylation; Epigenetic modification; Hippocampal neuron

Subject

Biology and Life Sciences, Neuroscience and Neurology

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