Melatonin Suppresses Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Signaling and Delays the Development of Hearing Loss in the C57BL/6J Presbycusis Mouse Model

被引：6

作者：

Liu, Jinlan ^{[1
,2
]}

Chen, Huiying ^{[1
]}

Lin, Xiaoyu ^{[1
]}

Zhu, Xiaoting ^{[1
]}

Huang, Jialin ^{[1
]}

Xu, Wenfeng ^{[1
]}

Tan, Ming ^{[1
]}

Su, Jiping ^{[1
]}

机构：

[1] Guangxi Med Univ, Afliated Hosp 1, Dept Otolaryngol Head & Neck Surg, Nanning, Guangxi, Peoples R China

[2] Guangxi Int Zhuang Med Hosp, Dept Otolaryngol Head & Neck Surg, Nanning, Guangxi, Peoples R China

来源：

NEUROSCIENCE | 2023年 / 517卷

基金：

中国国家自然科学基金;

关键词：

melatonin; inflammation; age-related hearing loss; cGAS-STING pathway; mitochondrial DNA; OXIDATIVE STRESS; MITOCHONDRIAL-DNA; INNER-EAR; INFLAMMATION; AGE; CGAS; DAMAGE; SENESCENCE; RELEASE; MTDNA;

D O I：

10.1016/j.neuroscience.2023.01.015

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

supplementation has been shown to delay age-related hearing loss (ARHL) progression. Pre-viously, melatonin was found to inhibit neuronal mitochondrial DNA (mtDNA) release, as well as inhibit cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling, thereby delaying the onset of cen-tral nervous system diseases. Therefore, we hypothesized that melatonin may delay the progression of hearing loss in the C57BL/6J presbycusis mouse model by inhibiting cGAS-STING signaling in the auditory pathway. Oral melatonin at 10 mg/kg/d was administered to 3-month-old C57BL/6J mice until 12 months of age. The auditory brainstem response (ABR) threshold was used to assess their hearing ability. By real-time polymerase chain reac-tion and Western blot analysis, the levels of cytosolic mtDNA, cGAS/STING, and cytokines were examined in the mouse cochlea, inferior colliculus, and auditory cortex. We found that the 12-month-old control mice exhibited significant hearing loss, increased cytosolic mtDNA, increased expression of inflammatory factors TNF-a, IL-6, IFN-b, Cxcl10, and Ifit3, up-regulated cGAS and STING expression, and enhanced interferon regulatory factor 3 (IRF3) phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. Melatonin treat-ment significantly improved hearing, decreased cytosolic mtDNA, suppressed the expression of inflammatory cytokines TNF-a, IL-6, IFN-b, Ifit3, and Cxcl10, down-regulated cGAS and STING expression, and attenuated IRF3 phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. This study sug-gested that melatonin had a protective effect on auditory function in the C57BL/6J presbycusis mouse model, which may be mediated through reducing mtDNA release, inhibiting the cGAS-STING signaling pathway in the auditory pathway.(c) 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：84 / 95

页数：12