N-Methyl-D-Aspartate Receptors Involvement in the Gentamicin-Induced Hearing Loss and Pathological Changes of Ribbon Synapse in the Mouse Cochlear Inner Hair Cells.

N-Methyl-D-Aspartate Receptors Involvement in the Gentamicin-Induced Hearing Loss and Pathological Changes of Ribbon Synapse in the Mouse Cochlear Inner Hair Cells.
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N-甲基-D-天冬氨酸受体参与庆大霉素引起的听力损失和小鼠耳蜗内毛细胞带状突触的病理变化

DOI:
10.1155/2018/3989201
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发表时间:
2018
期刊:
影响因子:
3.1
通讯作者:
Dai P
Dai P
中科院分区:
医学4区
文献类型:
--
作者:
Hong J;Chen Y;Zhang Y;Li J;Ren L;Yang L;Shi L;Li A;Zhang T;Li H;Dai P

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耳蜗内毛细胞(IHC)带状突触在声音编码和神经递质释放中起重要作用。以往的研究表明,噪声和氨基糖甙类药物的暴露均导致突触带的数量减少和形态改变。在这项工作中,我们确定了N-甲基-D-天冬氨酸受体(NMDARs)的分布及其在庆大霉素诱导的耳蜗IHC带状突触元件的病理变化中的作用。在正常成熟小鼠耳蜗中,NMDAR主要分布在耳蜗蜗轴侧,靠近耳蜗核区,而突触带和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPAR)主要分布在靠近耳蜗基底极的神经末梢。庆大霉素暴露后,NMDAR增加并向IHC基底极移动。同时,突触带和AMPAR向传入树突上的IHC束极移动。带状突触数量减少,并伴有听性脑干反应阈值升高和I波振幅降低。NMDAR拮抗剂MK 801治疗可减轻庆大霉素引起的听力损失和IHC带状突触的病理改变,提示NMDAR通过调节IHC带状突触的数量和分布参与庆大霉素引起的耳毒性。
Cochlear inner hair cell (IHC) ribbon synapses play an important role in sound encoding and neurotransmitter release. Previous reports show that both noise and aminoglycoside exposures lead to reduced numbers and morphologic changes of synaptic ribbons. In this work, we determined the distribution of N-methyl-D-aspartate receptors (NMDARs) and their role in the gentamicin-induced pathological changes of cochlear IHC ribbon synaptic elements. In normal mature mouse cochleae, the majority of NMDARs were distributed on the modiolar side of IHCs and close to the IHC nuclei region, while most of synaptic ribbons and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) were located on neural terminals closer to the IHC basal poles. After gentamicin exposure, the NMDARs increased and moved towards the IHC basal poles. At the same time, synaptic ribbons and AMPARs moved toward the IHC bundle poles on the afferent dendrites. The number of ribbon synapse decreased, and this was accompanied by increased auditory brainstem response thresholds and reduced wave I amplitudes. NMDAR antagonist MK801 treatment reduced the gentamicin-induced hearing loss and the pathological changes of IHC ribbon synapse, suggesting that NMDARs were involved in gentamicin-induced ototoxicity by regulating the number and distribution of IHC ribbon synapses.
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