南方科技大学陈放怡研究组在研究中取得进展。他们报道了利用声逃逸反应筛选斑马鱼侧线毛细胞保护剂的新功能方法。该研究于2025年5月6日发表于国际一流学术期刊《神经科学通报》杂志上。

斑马鱼幼鱼具有识别化学物质对侧线毛细胞（LL）损伤的敏感性，这种类型的化学筛选主要集中在寻找细胞死亡的保护剂。为了扩大HC保护器的候选池，开发了一种自建的声学逃逸响应（AER）检测系统，该系统同时应用了低频近场声音传输和AER图像采集/处理模块。该装置迅速确认了由大多数已知耳毒素、保护剂和神经传递修饰剂引起的LL HC功能的改变，或LL HC表达基因的敲低。通过串联10个装置，从124种细胞周期蛋白依赖性激酶抑制剂中鉴定出5种“命中”的化学物质，在不到一天的时间内部分恢复顺铂损伤的AER。其中AS2863619、ribociclib和SU9516对母鼠耳蜗中的HC有保护作用。因此，以自由游动的幼体斑马鱼为研究对象，自制的AER检测装置可以有效地识别出对HC损伤（包括细胞死亡和功能丧失）具有保护作用的化合物。

附：英文原文

Title: A Novel Functional Method of Protector Screening for Zebrafish Lateral Line Hair Cells via the Acoustic Escape Response

Author: Zheng, Ling, Shen, Qiaosen, Zhao, Tong, Liu, Qingsong, Huang, Zihao, Zhao, Feng, Zhang, Mengqian, Song, Yongdong, Zhang, Daogong, Liu, Dong, Chen, Fangyi

Issue&Volume: 2025-05-06

Abstract: Zebrafish larvae are useful for identifying chemicals against lateral line (LL) hair cell (HC) damage and this type of chemical screen mainly focuses on searching for protectors against cell death. To expand the candidate pool of HC protectors, a self-built acoustic escape response (AER)-detecting system was developed to apply both low-frequency near-field sound transmission and AER image acquisition/processing modules. The device quickly confirmed the changed LL HC functions caused by most known ototoxins, protectors, and neural transmission modifiers, or knockdown of LL HC-expressing genes. With ten devices wired in tandem, five ‘hit’ chemicals were identified from 124 cyclin-dependent kinase inhibitors to partially restore cisplatin-damaged AER in less than a day. AS2863619, ribociclib, and SU9516 among the hits, protected the HCs in the mouse cochlea. Therefore, using free-swimming larval zebrafish, the self-made AER-detecting device can efficiently identify compounds that are protective against HC damage, including cell death and loss-of-function.

DOI: 10.1007/s12264-025-01406-3

Source: https://link.springer.com/article/10.1007/s12264-025-01406-3