Recombinant human Neuritin protects cochlear ribbon synapses and hearing function via ERK1/2 activation post noise-induced injury

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2025-05-10 DOI:10.1016/j.bbrep.2025.102044

Haiyan Wang , Jinchi Hu , Shuangyan Liu , Fei Gui , Xiaopin Sun , Rong Chen , Guanwu Yin , Xiaoming Song , Yi Yang , Yu Hong

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Abstract

The preservation of synaptic integrity and physiological activity is pivotal for post-traumatic auditory rehabilitation following acoustic overexposure. Neuritin, a neurotrophic factor that facilitates synapse formation, maturation, and enhanced synaptic transmission, is essential for synapse development. In this study, we established a noise-induced cochlear synaptopathy model in CBA/CaJ mice, revealing a temporal association between endogenous Neuritin expression and synaptic density. Furthermore, administration of recombinant Human Neuritin (rhNeuritin) effectively preserves synaptic density in the cochlear basal turn at 7 days and 14 days following noise exposure. Importantly, it preserves the density of functional synapses (represented by overlapping CtBP2 and GluA2 puncta) and synapse function (indicated by ABR I wave amplitudes), thus diminishing the impairment of auditory function. In addition, rhNeuritin reverses the decrease in phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) levels resulting from noise exposure. By primarily preserving both the number and functionality of synapses in the basal turn, potentially via the induction of ERK1/2 phosphorylation, rhNeuritin mitigated hearing loss. These findings underscore the protective efficacy of rhNeuritin against noise-induced synaptic injury.

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重组人神经素通过ERK1/2激活保护耳蜗带突触和听力功能

突触完整性和生理活动的保存是关键创伤后听觉康复后的声音过度暴露。神经素是一种促进突触形成、成熟和增强突触传递的神经营养因子，对突触发育至关重要。在本研究中，我们建立了噪声诱导的CBA/CaJ小鼠耳蜗突触病模型，揭示了内源性Neuritin表达与突触密度之间的时间相关性。此外，在噪声暴露后7天和14天，重组人神经素（rhNeuritin）有效地保持了耳蜗基底转的突触密度。重要的是，它保留了功能性突触的密度（以重叠的CtBP2和GluA2点为代表）和突触的功能（以ABR I波幅度表示），从而减少了听觉功能的损害。此外，rhNeuritin还能逆转噪音暴露导致的磷酸化细胞外信号调节蛋白激酶1/2 （p-ERK1/2）水平的下降。rhNeuritin主要通过保持基底转突触的数量和功能，可能通过诱导ERK1/2磷酸化，减轻听力损失。这些发现强调了rhNeuritin对噪声诱导的突触损伤的保护作用。

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.