Mettl3-mA-NPY Axis Governing Neuron-microglia Interaction Regulates Sleep Amount of Mice

Overview

Journal Cell Discov

Date 2025 Feb 5

PMID 39905012

Authors

Qihang Sun

Jinpiao Zhu

Xingsen Zhao

Xiaoli Huang

Wenzheng Qu

Xia Tang

Daqing Ma

Qiang Shu

Xuekun Li

Affiliations

Soon will be listed here.

Abstract

Sleep behavior is regulated by diverse mechanisms including genetics, neuromodulation and environmental signals. However, it remains completely unknown regarding the roles of epitranscriptomics in regulating sleep behavior. In the present study, we showed that the deficiency of RNA mA methyltransferase Mettl3 in excitatory neurons specifically induces microglia activation, neuroinflammation and neuronal loss in thalamus of mice. Mettl3 deficiency remarkably disrupts sleep rhythm and reduces the amount of non-rapid eye movement sleep. We also showed that Mettl3 regulates neuropeptide Y (NPY) via mA modification and Mettl3 conditional knockout (cKO) mice displayed significantly decreased expression of NPY in thalamus. In addition, the dynamic distribution pattern of NPY is observed during wake-sleep cycle in cKO mice. Ectopic expression of Mettl3 and NPY significantly inhibits microglia activation and neuronal loss in thalamus, and restores the disrupted sleep behavior of cKO mice. Collectively, our study has revealed the critical function of Mettl3-mA-NPY axis in regulating sleep behavior.

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