Kanamycin ototoxicity in glutamate transporter knockout mice
Kanamycin ototoxicity in glutamate transporter knockout mice
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DOI：
10.1016/j.neulet.2005.01.066
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发表时间：
2005-06-03
影响因子：
2.5
通讯作者：
Gyo, K
中科院分区：
文献类型：
--
作者：
Shimizu, Y;Hakuba, H;Gyo, K
谷氨酸-天冬氨酸转运体（GLAST），一种强大的谷氨酸摄取。神经递质系统，从突触间隙中清除释放的谷氨酸，并促进谷氨酸作为神经递质再循环系统的再利用。氨基糖苷类药物引起的听力损失是通过谷氨酸兴奋毒性过程介导的。我们研究了GLAST基因敲除小鼠的氨基糖苷类耳毒性的影响，使用记录的听觉脑干反应（ABR）和耳蜗毛细胞的数量。将卡那霉素（100 mg/mL）直接注射到小鼠的后半规管中。在卡那霉素处理前，野生型和基因敲除小鼠之间的ABR阈值平均值没有差异。与野生型小鼠相比，卡那霉素使GLAST基因敲除小鼠ABR阈值升高，且GLAST基因敲除小鼠的IHC变性更严重。提示GLAST在预防氨基糖苷类耳中毒性内毛细胞变性中起重要作用。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Glutamate-aspartate transporter (GLAST), a powerful glutamate uptake. system, removes released glutamate from the synaptic cleft and facilitates the re-use of glutamate as a neurotransmitter recycling system. Aminoglycoside-induced hearing loss is mediated via a glutamate excitotoxic process. We investigated the effect of aminoglycoside ototoxicity in GLAST knockout mice using the recorded auditory brainstem response (ABR) and number of hair cells in the cochlea. Kanamycin (100 mg/mL) was injected directly into the posterior semicircular canal of mice. Before the kanamycin treatment, there was no difference in the ABR threshold average between the wild-type and knockout mice. Kanamycin injection aggravated the ABR threshold in the GLAST knockout mice compared with the wild-type mice, and the IHC degeneration was more severe in the GLAST knockout mice. These findings suggest that GLAST plays an important role in preventing the degeneration of inner hair cells in aminoglycoside ototoxicity. (c) 2005 Elsevier Ireland Ltd. All rights reserved.