Murashita Hidekazu, Tabuchi Keiji, Sakai Shuhei, Uemaetomari Isao, Tsuji Shigeki, Hara Akira
Department of Otolaryngology, Graduate School of Comprehensive Human Sciences, Majors of Functional and Regulatory Medical Sciences, University of Tsukuba, Tsukuba, Japan.
Neurosci Lett. 2007 May 11;418(1):18-21. doi: 10.1016/j.neulet.2007.02.060. Epub 2007 Mar 1.
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 4h. Muscimol and/or bicuculline, a GABA(A) 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 GABA(A) receptors reduces acoustic injury of the cochlea.
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，构成了耳蜗传出系统。谷氨酸兴奋性毒性与耳蜗听觉损伤的发病机制有关。本研究调查了GABA(A)激动剂蝇蕈醇是否能减轻听觉损伤。将小鼠暴露于128 dB SPL的4 kHz纯音下4小时。在听觉过度暴露开始前立即腹腔注射蝇蕈醇和/或GABA(A)拮抗剂荷包牡丹碱。然后评估听觉过度暴露后听觉脑干反应（ABR）的阈值变化和耳蜗形态。蝇蕈醇显著降低了ABR阈值变化，并抑制了听觉过度暴露引起的传入树突肿胀。此外，荷包牡丹碱抑制了蝇蕈醇的作用。这些发现表明，GABA(A)受体的激活可减轻耳蜗的听觉损伤。
