Zheng Ling, Shen Qiaosen, Zhao Tong, Liu Qingsong, Huang Zihao, Zhao Feng, Zhang Mengqian, Song Yongdong, Zhang Daogong, Liu Dong, Chen Fangyi
Harbin Institute of Technology, Harbin, 150001, Heilongjiang, China.
Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, China.
Neurosci Bull. 2025 May 6. doi: 10.1007/s12264-025-01406-3.
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.
斑马鱼幼体对于识别可防止侧线（LL）毛细胞（HC）损伤的化学物质很有用，并且这种类型的化学筛选主要侧重于寻找细胞死亡的保护剂。为了扩大HC保护剂的候选库，开发了一种自行构建的听觉逃逸反应（AER）检测系统，该系统应用了低频近场声音传输以及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、神经传递调节剂或LL HC表达基因的敲低所引起的LL HC功能变化。通过将十个装置串联连接，从124种细胞周期蛋白依赖性激酶抑制剂中鉴定出五种“有活性”化学物质，可在不到一天的时间内部分恢复顺铂损伤的AER。其中有活性的AS2863619、瑞博西尼和SU9516可保护小鼠耳蜗中的毛细胞。因此，使用自由游动的斑马鱼幼体，自制的AER检测装置可以有效地识别对HC损伤具有保护作用的化合物，包括防止细胞死亡和功能丧失。
