Kerstin Blum, Pauline Schepsky, Philip Derleder, Philipp Schätzle, Fahmi Nasri, Philipp Fischer, Jutta Engel, Simone Kurt
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引用次数: 0
Abstract
Noise-induced cochlear synaptopathy is characterized by irreversible loss of synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) despite normal hearing thresholds. We analyzed hearing performance and cochlear structure in C57BL/6 N mice exposed to 100, 106, or 112 dB SPL broadband noise (8-16 kHz) for 2 h. Auditory brainstem responses (ABRs) were assessed before, directly after, and up to 28 days post-trauma. Finally, the number, size, and pairing of IHC presynaptic (CtBP2-positive) ribbons and postsynaptic AMPA receptor scaffold (Homer1-positive) clusters were analyzed along the cochlea. Four weeks after the 100 dB SPL trauma, a permanent threshold shift (PTS) was observed at 45 kHz, which after the higher traumata extended toward middle to low frequencies. Loss in ABR wave I amplitudes scaled with trauma strength indicating loss of functional IHC synaptic connections. Latencies of wave I mostly increased with trauma strength. No trauma-related OHC loss was found. The number of synaptic pairs was reduced in the midbasal and basal cochlear region in all trauma conditions, with ribbon loss amounting up to 46% of control. Ribbons surviving the trauma were paired, whereas 4-6 unpaired postsynapses/IHC were found in the medial, midbasal, and basal regions irrespective of trauma strength, contrasting findings in CBA/CaJ mice. Our data confirm the susceptibility of ribbon synapses and ABR wave I amplitudes to a noise trauma of 100 dB SPL or larger. Notably, peripheral dendrites bearing IHC postsynapses were less vulnerable than presynaptic ribbons in C57BL/6 N mice.
噪声诱导的耳蜗突触病的特点是,尽管听阈正常,但内毛细胞(IHC)和螺旋神经节神经元(SGN)之间的突触会出现不可逆的损失。我们对暴露于 100、106 或 112 dB SPL 宽带噪声(8-16 kHz)2 小时的 C57BL/6 N 小鼠的听力表现和耳蜗结构进行了分析。最后,沿耳蜗分析了突触前(CtBP2阳性)IHC带和突触后AMPA受体支架(Homer1阳性)簇的数量、大小和配对情况。100 dB SPL创伤四周后,在45 kHz处观察到永久性阈值偏移(PTS),高创伤后向中低频延伸。ABR I 波振幅的损失与创伤强度成比例,表明功能性 IHC 突触连接的损失。I 波的延迟大多随创伤强度而增加。未发现与创伤相关的 OHC 损失。在所有创伤条件下,中基底和基底耳蜗区的突触对数量都减少了,带状突触损失高达对照组的 46%。创伤后存活下来的带状突触都是成对的,而在内侧、基底中层和基底区,无论创伤强度如何,都发现了 4-6 个未成对的后突触/IHC,这与 CBA/CaJ 小鼠的发现形成了鲜明对比。我们的数据证实了带状突触和 ABR 波 I 振幅易受 100 dB SPL 或更大噪声创伤的影响。值得注意的是,在 C57BL/6 N 小鼠中,带有 IHC 后突触的外周树突比突触前带突触更不容易受到影响。
期刊介绍:
Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.