Department of Biology, St. Mary's College of Maryland, 18952 E. Fisher Drive, St. Mary's City, MD 20686, USA.
J Clin Neurosci. 2012 Feb;19(2):333-5. doi: 10.1016/j.jocn.2011.06.008. Epub 2011 Nov 2.
In zebrafish neuromast hair cells, the process of programmed cell death ototoxic damage is strikingly similar to that of degenerating hair cells of the mammalian organ of Corti. Therefore, in vivo zebrafish assays involving the lateral line have been developed for drug ototoxicity screening. This is accomplished by examination of canal neuromast morphology in treated larvae using fluorescent dyes. To-date however, physiological confirmation of lateral line dysfunction resulting from such ototoxins has not been reported in the scientific literature--neither for larval nor adult zebrafish. Here we describe a rapid, non-invasive far-field electrophysiological method for assessing lateral line function. We suggest that ototoxic and otoprotective agents identified in larval studies may be assessed using this tool in adult fish. In this way, potential drug candidates can be further screened en route to testing in mammalian models, before potential clinical trials begin.
在斑马鱼毛细胞中,程序性细胞死亡的耳毒性损伤过程与哺乳动物耳蜗毛细胞的退化过程惊人地相似。因此,已经开发了涉及侧线的体内斑马鱼检测,用于药物耳毒性筛选。这是通过使用荧光染料检查处理幼虫的管毛形态来完成的。然而,迄今为止,在科学文献中尚未报道此类耳毒性物质引起的侧线功能障碍的生理确认——无论是幼虫还是成年斑马鱼。在这里,我们描述了一种快速、非侵入性的远场电生理学方法来评估侧线功能。我们建议,在成年鱼类中,可以使用该工具评估在幼虫研究中鉴定出的耳毒性和耳保护剂。通过这种方式,可以在开始临床试验之前,在哺乳动物模型中进行测试之前,对潜在的候选药物进行进一步筛选。