Noise-Induced Dysregulation ofQuakingRNA Binding Proteins Contributes to Auditory Nerve Demyelination and Hearing Loss

• DOI: 10.1523/jneurosci.2487-17.2018
• Publication Date: 2018-02-13T15:17:48Z
• Authors: Clarisse H. Panga...; Jeremy L. Barth; Lama Darbelli; Yazhi Xing; Jianning Zhang; Hui Li; Kenyaria V. Noble; Ting Liu; LaShardai N. Brown; Bradley A. Schulte; Stéphane Richard; Hainan Lang
• Keywords: Spiral ganglion

Noise exposure causes auditory nerve (AN) degeneration and hearing deficiency, though the proximal biological consequences are not entirely understood. Most AN fibers spiral ganglion neurons ensheathed by myelinating glia that provide insulation ensure rapid transmission of impulses from cochlea to brain. Here we show noise administered mice either sex rapidly affects glial cells, causing molecular cellular precede degeneration. This response is characterized demyelination, inflammation, widespread expression changes in myelin-related genes, including RNA splicing regulator Quaking (QKI) numerous QKI target genes. Analysis deficient revealed production cochlear cells essential for proper myelination fibers, normal hearing. Our findings implicate dysregulation as a critical early component response, influencing function leads demyelination and, ultimately, deficiency. SIGNIFICANCE STATEMENT Auditory ensheath majority with myelin, protect neurons, allow fast conduction electrical along nerve. dysfunction leading myelin abnormality altered genes nerve, QKI, gene implicated regulating myelination. Study conditional mouse model specifically depleted showed deficiency alone was sufficient elicit functional declines. These results establish key causative agent loss.