Surgery-free video-oculography in mouse models: enabling quantitative and short-interval longitudinal assessment of vestibular function. (23rd March 2019)

• Record Type: Journal Article
• Authors: Yang, Xiaojie; Zhou, Shiyue; Wu, Jiaojiao; Liao, Qun; Wang, Changquan; Liu, Minghua; Qu, Lei; Zhang, Yuan; Cheng, Cheng; Chai, Renjie; Zhang, Kun; Yu, Xiaojie; Huang, Pingbo; Liu, Lian; Xiong, Wei; Chen, Shi; Chen, Fangyi
• Is Part Of: Neuroscience letters. Volume 696(2019)
• Page Start: 212
• Page End: 218
• Publication Date: 2019-03-23
• Subjects: Vestibulo-ocular reflex (VOR) -- Behavioral assay -- Genetic screen -- 3, 3′-iminodipropionitrile (IDPN) -- Ototoxicity -- Vestibular function -- Video-oculography (VOG) -- Mouse model; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2018.12.036
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Surgery-free VOR measurement that allows screen for genes and drugs affecting vestibular function has been enabled. Daily-progression profile of the vestibular impairment caused by IDPN at different dose levels has been obtained. Mice with homozygous mutations of Lhfpl5 and Cdh23 have been identified based on their reduced VOR-response levels. Abstract: Vestibulo-ocular reflex (VOR) responding to acceleration stimuli is originated from the vestibular apparatuses and thus widely used as an in vivo indicator of the vestibular function. We have developed a vestibular function testing (VFT) system that allows to evaluate VOR response with improved efficiency. The previously required surgical procedure has been avoided by using a newly designed animal-immobility setup. The efficacy of our VFT system was demonstrated on the mice with vestibular abnormalities caused by either genetic mutations ( Lhfpl5 −/− or Cdh23 −/− ) or applied vestibulotoxicant (3, 3′-iminodipropionitrile, IDPN). Daily longitudinal inspection of the VOR response in the IDPN-administered mice gives the first VOR-based daily-progression profile of the vestibular impairment. The capability of VOR in quantifying the severity of toxicant-induced vestibular deficits has been also demonstrated. The acquired VOR-measurement results were validated against the corresponding behavioral-test results. Further validation against immunofluorescence microscopy was applied to the VOR data obtained from the IDPN-administered mice. We conclude that the improved efficiency of our surgery-free VFT system, firstly, enables the characterization of VOR temporal dynamics and quantification of vestibular-impairment severity that may reveal useful information in toxicological and/or pharmaceutical studies; and, secondly, confers our system promising potential to serve as a high-throughput screener for identifying genes and drugs that affect vestibular function.