The effect of a GABAA agonist muscimol on acoustic injury of the mouse cochlea
The effect of a GABAA agonist muscimol on acoustic injury of the mouse cochlea
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DOI：
10.1016/j.neulet.2007.02.060
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发表时间：
2007-05-11
影响因子：
2.5
通讯作者：
Hara, Akira
中科院分区：
文献类型：
--
作者：
Murashita, Hidekazu;Tabuchi, Keiji;Hara, Akira
γ -氨基丁酸（GABA）是中枢神经系统中主要的抑制性神经递质之一，构成耳蜗传出系统。谷氨酸兴奋性毒性与耳蜗听觉损伤的发病机制有关。本文研究GABA(A)激动剂muscimol是否能减轻听觉损伤。小鼠暴露于128 dB SPL的4 kHz纯音中4小时。在声学过度暴露开始前立即腹腔注射Muscimol和/或bicuculline（一种GABAA拮抗剂）。观察过度暴露后听性脑干反应（ABR）和耳蜗形态的阈值变化。Muscimol显著降低ABR阈值移位，抑制传入树突过度暴露引起的肿胀。此外，二胡碱还能抑制muscimol的作用。这些发现表明GABAA受体的激活可以减轻耳蜗的听觉损伤。2007爱思唯尔爱尔兰有限公司版权所有。
Gamma-aminobutyric acid (GABA) is one of major inhibitory neurotransmitter in the central nervous system and constitutes the cochlear efferent system. Glutamate excitotoxicity is implicated in the pathogenesis of acoustic injury of the cochlea. The present work investigated whether GABA(A) agonist muscimol can alleviate acoustic injury. Mice were exposed to a 4 kHz pure tone of 128 dB SPL for 4 h. Muscimol and/or bicuculline, a GABAA antagonist, were intraperitoneally administered immediately before the onset of acoustic overexposure. The threshold shifts of the auditory brainstem response (ABR) and cochlear morphology after acoustic overexposure were then evaluated. Muscimol significantly decreased the ABR threshold shift and inhibited swelling of the afferent dendrites induced by acoustic overexposure. In addition, bicuculline inhibited the effects of muscimol. These findings suggest that activation of GABAA receptors reduces acoustic injury of the cochlea. (c) 2007 Elsevier Ireland Ltd. All rights reserved.