Early Physiological and Cellular Indicators of Cisplatin-Induced Ototoxicity

被引:11
作者
Chen, Yingying [1 ,2 ]
Bielefeld, Eric C. [3 ]
Mellott, Jeffrey G. [1 ]
Wang, Weijie [1 ,4 ]
Mafi, Amir M. [1 ]
Yamoah, Ebenezer N. [2 ]
Bao, Jianxin [1 ]
机构
[1] Northeast Ohio Med Univ, Dept Neurobiol & Anat, Translat Res Ctr, Rootstown, OH 44272 USA
[2] Univ Nevada, Dept Physiol & Cell Biol, Reno, NV 95616 USA
[3] Ohio State Univ, Dept Speech & Hearing Sci, 110 Pressey Hall,1070 Carmack Rd, Columbus, OH 43210 USA
[4] Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
来源
JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY | 2021年 / 22卷 / 02期
关键词
cisplatin; ototoxicity; hair cells; spiral ganglion neuron; Schwann cell; INDUCED HEARING-LOSS; PRODUCT OTOACOUSTIC EMISSIONS; PATIENTS RECEIVING CISPLATIN; CHEMOTHERAPY; MECHANISMS; NEUROTOXICITY; DEGENERATION; MORPHOLOGY; NEUROPATHY; INCREASES;
D O I
10.1007/s10162-020-00782-z
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Cisplatin chemotherapy often causes permanent hearing loss, which leads to a multifaceted decrease in quality of life. Identification of early cisplatin-induced cochlear damage would greatly improve clinical diagnosis and provide potential drug targets to prevent cisplatin's ototoxicity. With improved functional and immunocytochemical assays, a recent seminal discovery revealed that synaptic loss between inner hair cells and spiral ganglion neurons is a major form of early cochlear damage induced by noise exposure or aging. This breakthrough discovery prompted the current study to determine early functional, cellular, and molecular changes for cisplatin-induced hearing loss, in part to determine if synapse injury is caused by cisplatin exposure. Cisplatin was delivered in one to three treatment cycles to both male and female mice. After the cisplatin treatment of three cycles, threshold shift was observed across frequencies tested like previous studies. After the treatment of two cycles, beside loss of outer hair cells and an increase in high-frequency hearing thresholds, a significant latency delay of auditory brainstem response wave 1 was observed, including at a frequency region where there were no changes in hearing thresholds. The wave 1 latency delay was detected as early cisplatin-induced ototoxicity after only one cycle of treatment, in which no significant threshold shift was found. In the same mice, mitochondrial loss in the base of the cochlea and declining mitochondrial morphometric health were observed. Thus, we have identified early spiral ganglion-associated functional and cellular changes after cisplatin treatment that precede significant threshold shift.
引用
收藏
页码:107 / 126
页数:20
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