星形胶质细胞在噪声损伤后小鼠耳蜗核突触修复中的作用
Role of astrocytes in the repair of auditory synapses in the cochlear nucleus after noise damage
周卫军 1刘思迪 1蔡瑞捷 1刘宏超 1王美建 1吴皓 1刘辉辉 1汪照炎1
作者信息
- 1. 上海交通大学医学院附属第九人民医院耳鼻咽喉头颈外科,上海 200011;上海交通大学医学院耳科学研究所,上海 200125;上海市耳鼻疾病转化医学重点实验室,上海 200125
- 折叠
摘要
目的·通过形态学分析和分子生物学技术,探究噪声引起的耳蜗核损伤的病理生理变化以及星形胶质细胞对损伤的调节功能.方法·将48只C57BL/6J雄性小鼠随机分成2组暴露在110 dB声压级(sound pressure level,SPL)的宽频噪声下,持续2h.然后在噪声暴露后的第1、7、14、30和90日对小鼠进行听性脑干反应(auditory brainstem response,ABR)测试;并对耳蜗核组织进行免疫荧光染色观察耳蜗核神经元、听觉突触损伤情况以及星形胶质细胞激活程度;此外,通过蛋白质印迹法(Western blotting)进一步验证噪声对耳蜗核神经元与神经突触的损伤情况.结果·噪声暴露后,腹侧耳蜗核中丛细胞数量显著减少.Western blotting结果显示耳蜗核神经元中神经纤维严重丢失,表明噪声对耳蜗核神经元造成了严重的损害.囊泡谷氨酸转运蛋白1(vesicular glutamate transporter 1,Vglutl)标记的听觉神经突触明显丧失,其中在噪声暴露后的第14日丧失最为严重,随后在第90日呈缓慢恢复趋势.此外,在噪声暴露后,耳蜗核中星形胶质细胞呈现出明显的聚集和激活.通过胶质酸性纤维蛋白(glial fibrillary acidic protein,GFAP)染色,提示在噪声暴露之前,大多数星形胶质细胞分布在耳蜗核的周边、颗粒细胞区和听觉神经根周围,并且形态较小.然而,在噪声暴露后的第14 日,腹侧耳蜗核中大量激活的星形胶质细胞积聚,并且它们都表现出在突触周围生长的模式.结论·噪声暴露导致耳蜗核神经突触损伤,星形胶质细胞可能参与其损伤和修复过程.这些研究结果将为进一步理解耳蜗核中声音信号分析、整合和神经可塑性的机制提供关键基础.
Abstract
Objective·To investigate the pathological and physiological changes underlying noise-induced cochlear nucleus damage and the regulating function of astrocytes on the damage,using a combination of morphological analysis,and molecular biology techniques.Methods·Forty-eight male C57BL/6J mice were randomly divided into two groups and exposed to 110 dB SPL(sound pressure level)broadband noise for 2 hours.Auditory brainstem response(ABR)tests were performed on the mice on days 1,7,14,30,and 90 after the noise exposure.Immunofluorescence staining of cochlear nuclear tissue was conducted to observe cochlear nuclear neurons and auditory synapses,as well as astrocyte activation levels.In addition,the damage to the cochlear nuclear neurons and synapses caused by noise was verified through Western blotting.Results·A significant decrease in cochlear nuclear Bushy cells after noise exposure was observed.The Western blotting results showed that there was severe loss of nerve fibers in cochlear nuclear neurons,indicating that noise caused significant damage to cochlear nucleus neurons.Moreover,a significant loss of auditory synapses labeled with vesicular glutamate transporter 1(Vglutl)was observed,which was the severest on day 14 after noise exposure and slowly recovered on day 90.Interestingly,astrocytes in the cochlear nucleus displayed obvious clustering and activation after noise exposure.By staining with glial fibrillary acidic protein(GFAP),most astrocytes were distributed around the cochlear nucleus,granule cell area,and auditory nerve root before noise exposure,and they had a small size.However,on day 14 after noise exposure,a large number of activated astrocytes aggregated in the ventral cochlear nucleus,and they all showed a pattern of growth around the synapses.Conclusion·Noise exposure leads to significant damage in the cochlear nucleus,and it is possible that astrocytes are involved in its damage and repair processes.These findings will provide a crucial foundation for further understanding the mechanisms of sound signal analysis,integration,and neural plasticity in the cochlear nucleus.
关键词
噪声性聋/耳蜗核/星形胶质细胞/突触可塑性Key words
noise-induced hearing loss/cochlear nucleus/astrocytes/synaptic plasticity引用本文复制引用
基金项目
国家自然科学基金青年科学基金(82101211)
黄浦区产业扶持基金(XK2019011)
上海市科委"科技创新行动计划"基础研究领域项目(21JC1404000)
上海市耳鼻疾病转化医学重点实验室项目(14DZ2260300)
出版年
2024
国家科技期刊平台
NSTL
万方数据