CXCR2缺陷通过改变兴奋性损害螺旋神经节神经元的听觉功能
CXCR2 deficiency impairs auditory function in spiral ganglion neurons by altering excitability.
文献信息
| PMID | 42957635 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Fuyu Xian |
| 作者单位 | Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang, China. |
| 期刊 | Cell death discovery |
| SCI 分区 | Q1 |
| IF | 9.3 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 耳科 |
中文摘要
背景： CXC趋化因子受体2（CXCR2）是趋化因子受体家族的关键成员，在调节免疫和炎症反应中发挥核心作用。炎症已被确立为多种听觉疾病的关键病理因素，包括噪声性听力损失、药物性耳毒性和年龄相关性听力损失；然而，CXCR2在参与听觉信号转导的关键细胞中的表达模式和生物学功能仍不清楚。方法：在此，我们证明CXCR2在耳蜗螺旋神经节神经元（SGN）、毛细胞和血管纹中大量表达。结果：CXCR2的基因缺失导致小鼠进行性听力损失。来自CXCR2敲除小鼠的SGN表现出Kv1.2钾通道表达增加、带状突触受损和髓鞘完整性改变。电生理分析显示，CXCR2缺陷的SGN中Kv1电流增强且兴奋性显著降低。值得注意的是，使用腺相关病毒在SGN中敲低CXCR2重现了听力损失表型。结论：总之，我们的研究结果表明，CXCR2通过调节SGN兴奋性对听力至关重要。
英文摘要
CXC chemokine receptor 2 (CXCR2), a key member of the chemokine receptor family, plays a central role in regulating immune and inflammatory responses. Inflammation has been established as a critical pathological factor in various auditory disorders, including noise-induced hearing loss, drug-induced ototoxicity, and age-related hearing loss; however, the expression patterns and biological functions of CXCR2 in key cells involved in auditory signal transduction remain unclear. Here, we demonstrated that CXCR2 is abundantly expressed in cochlear spiral ganglion neurons (SGNs), hair cells, and the stria vascularis. Genetic deletion of CXCR2 resulted in progressive hearing loss in mice. SGNs from CXCR2 knockout mice exhibited increased expression of the Kv1.2 potassium channel, impaired ribbon synapses, and altered myelin integrity. Electrophysiological analysis revealed enhanced Kv1 currents and significantly reduced excitability in CXCR2-deficient SGNs. Notably, CXCR2 knockdown in SGNs using an adeno-associated virus recapitulated the hearing loss phenotype. In conclusion, our findings revealed that CXCR2 is essential for hearing as it regulates SGN excitability.