New insights into glutamate ototoxicity in cochlear hair cells and spiral ganglion neurons
New insights into glutamate ototoxicity in cochlear hair cells and spiral ganglion neurons
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关于谷氨酸对耳蜗毛细胞和螺旋神经节神经元的耳毒性的新见解
DOI：
10.3109/00016489.2010.495133
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发表时间：
2010-12-01
影响因子：
1.4
通讯作者：
Gong, Shusheng
中科院分区：
文献类型：
--
作者：
Lu, Haitao;Wang, Xiang;Gong, Shusheng
结论：过量谷氨酸(Glu)暴露于耳蜗外淋巴液中(20 MM)，在2 h内影响外毛细胞的生理功能，并以细胞凋亡诱导因子(AIF)依赖的方式诱导蜗牛螺旋神经节神经元(SGN)的凋亡。目的：探讨大剂量谷氨酸对耳蜗神经节细胞功能的影响及其诱导AIF和caspase-3依赖性细胞凋亡的作用。方法：成年豚鼠耳蜗行Glu(20 MM)和人工外淋巴液(AP)外淋巴灌流。分别于灌流前和灌流后2 h测定耳蜗微音素(CM)和电听觉脑干反应(EABR)。用透射电子显微镜观察毛细胞的形态。灌流后8h检测AIF和caspase-3两种细胞凋亡指标的表达。结果：与AP灌流相比，灌流20 mM Glu使CM和eABR波幅显著降低。谷氨酸灌流后内毛细胞变形，突触后区出现空泡化，而内毛细胞系统未受影响。谷氨酸暴露后8h，神经节细胞核内可见AIF的表达，而caspase-3在所有组织中均未见表达。
Abstract Conclusion: Excess glutamate (Glu) exposure (20 mM) in the cochlear perilymph affects the physiological function of outer hair cells (OHCs) within a 2 h period and induces apoptosis in the modiolus spiral ganglion neurons (SGNs) in an apoptosis-inducing factor (AIF)-dependent manner. Objectives: To determine whether high-dose Glu affects the function of OHCs and whether it induces AIF- and caspase-3-dependent apoptosis in the cochlear SGNs. Methods: Perilymphatic perfusions of Glu (20 mM) and artificial perilymph (AP) solutions were performed in adult guinea pig cochleae. Both cochlear microphonics (CM) and electrical auditory brainstem response (eABR) were measured before and 2 h after perfusions. The hair cell morphologies were examined using transmission electron microscopy. The expression of two apoptotic indicators, AIF and caspase-3, was examined 8 h after perfusions. Results: In contrast to AP perfusions, the perfusion of 20 mM Glu caused significant reduction in the CM and eABR amplitudes. Inner hair cells (IHCs) after Glu perfusion were deformed and exhibited vacuolization in the postsynaptic region, whereas the OHC system appeared unaffected. AIF expression was detected in the nuclei of SGNs 8 h after Glu exposure, but the expression of caspase-3 was not shown in any cochlear tissues.