Noise-induced Hearing Loss: Changes in Gene Expression in the Auditory Pathway
thesisposted on 2018-01-16, 16:13 authored by Sherylanne Newton
Noise induced hearing loss is classically divided into permanent or temporary forms. Individuals with permanent threshold shifts (PTS) will permanently lose auditory sensitivity, whereas individuals with temporary threshold shifts (TTS) will experience elevated hearing thresholds immediately following noise exposure, which resolves over several weeks. TTS causes little lasting damage to the hair cell, stereocilia or supporting structures which form the organ of Corti within the inner ear, and was therefore considered “no harm, no foul”. However, recent evidence suggests that TTS and PTS also leads to, what has been termed, “silent damage”; neuropathic damage which causes the loss of synaptic innervation at the inner hair cell and a slowly developing neuronal death. This study investigates the gene expression changes which accompany this type of noise-induced damage in the spiral ganglion neuron (SGN). Previous studies of gene expression changes following noise insult have used whole cochlea preparations which do not differentiate between changes in different cochlear structures. Here we have used micro-dissection of the modiolus to focus on the SGNs and to minimise contribution from other cochlea structures. In order to maximise the amount of data collected from each experimental animal, cochlear nucleus (CN) samples were taken in parallel to look at noise-induced changes at this first region of the central auditory system. A 1.5hr noise exposure of 105 dB SPL broadband noise elicited a moderate form of PTS, characterized by an immediate threshold shift of up to 44 dB SPL, which partially recovers over 28 days. Tissue was collected at 1day, 7days and 28days following exposure and RNA-Sequencing was performed. Over the 28-day period 421 genes were significantly changed in the modiolus; these were suggestive of a chronic immune response and for the first time, fibrinogen and lipid dysregulation. In the cochlear nucleus, just 184 genes were altered over 28-days; changes to Trpv4, Trpm3 and TrkA may contribute to increases in cell excitability in the CN following noise exposure.
Supervisor(s)Grubb, Blair; Forsythe, Ian; Straub, Volko
Date of award2017-12-15
Author affiliationDepartment of Neuroscience, Psychology and Behaviour
Awarding institutionUniversity of Leicester