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

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 develo...

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Main Authors: Haiyan Wang, Jinchi Hu, Shuangyan Liu, Fei Gui, Xiaopin Sun, Rong Chen, Guanwu Yin, Xiaoming Song, Yi Yang, Yu Hong
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Biochemistry and Biophysics Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2405580825001311
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Summary: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.
ISSN:2405-5808