Hair Cell Toxicity

毛细胞毒性

基本信息

批准号：
6883871
负责人：
Felipe Santos
金额：
$ 4.38万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-08-01 至 2005-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6883871
关键词：
alternatives to animals in research aminoglycoside antibiotics cellular pathology cisplatin cytotoxicity developmental neurobiology difluoromethylornithine disease /disorder model drug adverse effect drug screening /evaluation ear hair cell fluorescence microscopy gentamicins larva lateral line neomycin neural transmission neurotoxicology ototoxin postdoctoral investigator sensorineural hearing loss time resolved data transmission electron microscopy zebrafish

alternatives to animals in research aminoglycoside antibiotics cellular pathology cisplatin cytotoxicity developmental neurobiology difluoromethylornithine disease /disorder model drug adverse effect drug screening /evaluation ear hair cell fluorescence microscopy gentamicins larva lateral line neomycin neural transmission neurotoxicology ototoxin postdoctoral investigator sensorineural hearing loss time resolved data transmission electron microscopy zebrafish

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项目摘要

DESCRIPTION (provided by applicant): Drug-induced sensory hair cell death is a preventable cause of sensorineural hearing loss and vestibular toxicity. The objectives of this research are to better understand the cellular events involved in drug mediated hair cell death and to test if the zebrafish lateral line can be used as a model to predict ototoxicity. The sequence of cellular events leading to hair cell death or survival in the lateral line of zebrafish will be investigated using in vivo time-lapse fluorescence imaging and TEM ultrastructural analysis. Differences in mechanotransduction-dependent activity and aminoglycoside entry will be assayed in hair cells. The utility of this model to predict hair cell death will be determined, with a long-term goal of establishing a system for pre-clinical assessment of drugs.

描述（由申请人提供）：药物引起的感觉毛细胞死亡是感官听力丧失和前庭毒性的可预防原因。这项研究的目标是更好地了解药物介导的毛细胞死亡中涉及的细胞事件，并测试斑马鱼侧向线是否可以用作预测耳毒性的模型。将使用体内延时荧光成像和TEM超微结构分析来研究导致毛细胞死亡或生存的细胞事件序列。机械转导依赖性活性和氨基糖苷进入的差异将在毛细胞中测定。将确定该模型预测毛细胞死亡的实用性，其长期目标是建立用于药物临床前评估的系统。