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在C57BL/6J小鼠内毛细胞带状突触中,庆大霉素暴露导致otoferlin表达模式中断。

A pattern of otoferlin expression interrupted by gentamicin exposure in ribbon synapse of inner hair cell in C57BL/6J mice.

作者信息

ShuNa Li, Zhong Ren, Ke Liu

机构信息

The Department of Otolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, China.

出版信息

Acta Neurol Belg. 2009 Sep;109(3):221-5.

PMID:19902817
Abstract

Despite ototoxic effect of aminoglycosides on auditory sensory system has been well documented, the mechanism of ototoxic damage on synaptic connection (ribbon synapse) between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) is still largely unknown. Otoferlin is essential for a late step in exocytosis of neurotransmitter at ribbon synapses. In this study, C57BL/6J mice were intraperitoneally injected with gentamicin (100 mg/kg) once a day, the apical coils of organ of Corti were obtained at the 4th day, the 7th day and the 10th day respectively (n = 10/per group), the normal mice without a Gentamicin exposure were set for control (n = 10/per group). Otoferlin was detected by both immunofluorescence and western blotting. The hearing thresholds were measured by auditory brainstem responses (ABR). The expression of Otoferlin was up-regulated during the period of first 7days with a Gentamicin exposure. The down-regulation of Otoferlin expression was found after the 7th day with a gentamicin exposure. The hearing thresholds showed a linear increase. Gentamicin exposure may enhance transiently the expression of Otoferlin in ribbon synapse in C57BL/6J mice. This property might correlate with the ribbon synaptic plasticity in C57BL/6J mice. It may provide us a new insight for a further detailed study of the ribbon synaptic plasticity under the condition of aminoglycosides application.

摘要

尽管氨基糖苷类药物对听觉感觉系统的耳毒性作用已有充分记录,但对内毛细胞(IHC)与螺旋神经节神经元(SGN)之间突触连接(带状突触)的耳毒性损伤机制仍 largely 未知。 otoferlin 对于带状突触处神经递质胞吐的后期步骤至关重要。在本研究中,C57BL/6J 小鼠每天腹腔注射庆大霉素(100mg/kg)一次,分别在第 4 天、第 7 天和第 10 天获取 Corti 器的顶回(每组 n = 10),将未暴露于庆大霉素的正常小鼠设为对照(每组 n = 10)。通过免疫荧光和蛋白质印迹法检测 otoferlin。通过听性脑干反应(ABR)测量听力阈值。在暴露于庆大霉素的前 7 天期间,otoferlin 的表达上调。在暴露于庆大霉素 7 天后发现 otoferlin 表达下调。听力阈值呈线性增加。庆大霉素暴露可能会短暂增强 C57BL/6J 小鼠带状突触中 otoferlin 的表达。这一特性可能与 C57BL/6J 小鼠的带状突触可塑性相关。它可能为在氨基糖苷类药物应用条件下进一步详细研究带状突触可塑性提供新的见解。

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Ribbon Synapses and Hearing Impairment in Mice After in utero Sevoflurane Exposure.子宫内七氟醚暴露后小鼠的带状突触和听力损伤。
Drug Des Devel Ther. 2020 Jul 8;14:2685-2693. doi: 10.2147/DDDT.S253031. eCollection 2020.
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Partial Aminoglycoside Lesions in Vestibular Epithelia Reveal Broad Sensory Dysfunction Associated with Modest Hair Cell Loss and Afferent Calyx Retraction.
前庭上皮中的部分氨基糖苷类损伤揭示了与适度毛细胞丢失和传入杯状细胞退缩相关的广泛感觉功能障碍。
Front Cell Neurosci. 2017 Oct 27;11:331. doi: 10.3389/fncel.2017.00331. eCollection 2017.
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Spontaneous and Partial Repair of Ribbon Synapse in Cochlear Inner Hair Cells After Ototoxic Withdrawal.耳毒性药物停用后耳蜗内毛细胞带状突触的自发和部分修复
Mol Neurobiol. 2015 Dec;52(3):1680-1689. doi: 10.1007/s12035-014-8951-y. Epub 2014 Nov 7.
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Cochlear inner hair cell ribbon synapse is the primary target of ototoxic aminoglycoside stimuli.耳蜗内毛细胞带状突触是耳毒性氨基糖苷类刺激物的主要靶标。
Mol Neurobiol. 2013 Dec;48(3):647-54. doi: 10.1007/s12035-013-8454-2. Epub 2013 Apr 20.