A Novel Functional Method of Protector Screening for Zebrafish Lateral Line Hair Cells via the Acoustic Escape Response
Ling Zheng1,2 · Qiaosen Shen3 · Tong Zhao2 · Qingsong Liu2 · Zihao Huang2 · Feng Zhao4 · Mengqian Zhang2 · Yongdong Song5 · Daogong Zhang5,6,7 · Dong Liu3 · Fangyi Chen2,81 Harbin Institute of Technology, Harbin 150001, Heilongjiang, China
2 Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, China
3 School of Life Science, Southern University of Science and Technology, Shenzhen 518055, China
4 Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250000, China
5 Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan 250000, China
6 Shandong Provincial Vertigo & Dizziness Medical Center, Jinan 250000, China
7 Vertigo Disease Research Lab, Shandong Institute of Otorhinolaryngology, Jinan 250000, China
8 Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen 518055, China
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.
Keywords
Acoustic escape response; Zebrafsh; Lateral line; Hair cell; Low-frequency sound; Functional screening
