Toxic Effects of 3,3 '-Iminodipropionitrile on Vestibular System in Adult C57BL/6J Mice In Vivo

Zeng, Shan1,2,3; Ni, Wenli1,2,3; Jiang, Hui1,2; You, Dan1,2,3; Wang, Jinghan1,2,3; Lu, Xiaoling1,2,3; Liu, Liman3,4; Yu, Huiqian1,2,3; Wu, Jingfang1,2,3; Chen, Fangyi5; Li, Huawei1,2,3; Wang, Yunfeng1,2,3; Chen, Yan1,2,3; Li, Wenyan1,2,3

2020-07-03

10.1155/2020/1823454

NEURAL PLASTICITY   影响因子和分区

2090-5904

1687-5443

The utricle is one of the five sensory organs in the mammalian vestibular system, and while the utricle has a limited ability to repair itself, this is not sufficient for the recovery of vestibular function after hair cell (HC) loss induced by ototoxic drugs. In order to further explore the possible self-recovery mechanism of the adult mouse vestibular system, we established a reliable utricle epithelium injury model for studying the regeneration of HCs and examined the toxic effects of 3,3'-iminodiproprionitrile (IDPN) on the utricle in vivo in C57BL/6J mice, which is one of the most commonly used strains in inner ear research. This work focused on the epithelial cell loss, vestibular dysfunction, and spontaneous cell regeneration after IDPN administration. HC loss and supporting cell (SC) loss after IDPN treatment was dose-dependent and resulted in dysfunction of the vestibular system, as indicated by the swim test and the rotating vestibular ocular reflex (VOR) test. EdU-positive SCs were observed only in severely injured utricles wherein above 47% SCs were dead. No EdU-positive HCs were observed in either control or injured utricles. RT-qPCR showed transient upregulation of Hes5 and Hey1 and fluctuating upregulation of Ax in 2 and beta-caten in after IDPN administration. We conclude that a single intraperitoneal injection of IDPN is a practical way to establish an injured utricle model in adult C57BL/6J mice in vivo. We observed activation of Notch and Wnt signaling during the limited spontaneous HC regeneration after vestibular sensory epithelium damage, and such signaling might act as the promoting factors for tissue self-repair in the inner ear.

SCI

英语

其他

National Science Foundation for Outstanding Young People[81922018] ; National Natural Science Foundation of China[81771011][81700910][81700914] ; Development Fund for Shanghai Talents[2017046] ; Excellent Personnel Training Plan for the Shanghai Health System[2017Q003]

Neurosciences & Neurology

Neurosciences

WOS:000552798100002

HINDAWI LTD

NEUROSCIENCE & BEHAVIOR

Web of Science

1.Fudan Univ, ENT Inst, Shanghai 200031, Peoples R China
2.Fudan Univ, Otorhinolaryngol Dept, Affiliated Eye & ENT Hosp, State Key Lab Med Neurobiol, Shanghai 200031, Peoples R China
3.Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China
4.Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou 510080, Peoples R China
5.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen 518055, Guangdong, Peoples R China

Zeng, Shan,Ni, Wenli,Jiang, Hui,et al. Toxic Effects of 3,3 '-Iminodipropionitrile on Vestibular System in Adult C57BL/6J Mice In Vivo[J]. NEURAL PLASTICITY,2020,2020.

Zeng, Shan.,Ni, Wenli.,Jiang, Hui.,You, Dan.,Wang, Jinghan.,...&Li, Wenyan.(2020).Toxic Effects of 3,3 '-Iminodipropionitrile on Vestibular System in Adult C57BL/6J Mice In Vivo.NEURAL PLASTICITY,2020.

Zeng, Shan,et al."Toxic Effects of 3,3 '-Iminodipropionitrile on Vestibular System in Adult C57BL/6J Mice In Vivo".NEURAL PLASTICITY 2020(2020).