title: Ototrauma induces sodium channel plasticity in auditory afferent neurons.
abstract: Exposure to intense sound can cause damage to the delicate sensory and neuronal components of the cochlea leading to hearing loss. Such damage often causes the dendrites of the spiral ganglion neurons (SGN), the neurons that provide the afferent innervation of the hair cells, to swell and degenerate thus damaging the synapse. In models of neuropathic pain, axotomy, another form of afferent nerve damage, is accompanied by altered voltage-gated sodium channel (VGSC) expression, leading to neuronal hyperactivity. In this study, adult Wistar rats were exposed to noise which produced a mild, 20 dB hearing threshold elevation and their VGSC expression was investigated. Quantitative PCR showed decreased Na(V)1.1 and Na(V)1.6 mRNA expression in the SGN following noise exposure (29% and 56% decrease respectively) while Na(V)1.7 mRNA expression increased by approximately 20% when compared to control rats. Immunohistochemistry extended these findings, revealing increased staining for Na(V)1.1 along the SGN dendrites and Na(V)1.7 in the cell bodies after noise. These results provide the first evidence for selective changes in VGSC expression following moderate noise-induced hearing loss and could contribute to elevated hearing thresholds and to the generation of perceptual anomalies commonly associated with cochlear damage, such as tinnitus and hyperacusis.
authors.affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, LE1 9HN UK. agf4@le.ac.uk
authors.forename: Alistair G
authors.initials: AG
authors.lastname: Fryatt
authors.forename: Mike
authors.initials: M
authors.lastname: Mulheran
authors.forename: Julie
authors.initials: J
authors.lastname: Egerton
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Gunthorpe
authors.forename: Blair D
authors.initials: BD
authors.lastname: Grubb
mesh_terms: D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D003051:Cochlea / Q000166:cytology / Q000473:pathology / Q000502:physiology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D006198:Hair Cells, Auditory / Q000166:cytology / Q000502:physiology*; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013136:Spiral Ganglion / Q000166:cytology
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; C568250:Scn1a protein, rat; C507811:Scn8a protein, rat; C503480:Scn9a protein, rat; D015222:Sodium Channels