Axonal sprouting in the dorsal cochlear nucleus affects gap‑prepulse inhibition following noise exposure

Han,Kyu‑Hee; Mun,Seog‑Kyun; Sohn,Seonyong; Piao,Xian‑Yu; Park,Ilyong; Chang,Munyoung

doi:10.3892/ijmm.2019.4316

Axonal sprouting in the dorsal cochlear nucleus affects gap‑prepulse inhibition following noise exposure

Authors:
- Kyu‑Hee Han
- Seog‑Kyun Mun
- Seonyong Sohn
- Xian‑Yu Piao
- Ilyong Park
- Munyoung Chang
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Affiliations: Department of Otorhinolaryngology, National Medical Center, Seoul 04564, Republic of Korea, Department of Otorhinolaryngology‑Head and Neck Surgery, Chung‑Ang University College of Medicine, Seoul 06974, Republic of Korea, Department of Biomedical Engineering, Dankook University College of Medicine, Cheonan 31116, Republic of Korea
Published online on: August 19, 2019 https://doi.org/10.3892/ijmm.2019.4316
Pages: 1473-1483
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

One of the primary theories of the pathogenesis of tinnitus involves maladaptive auditory‑somatosensory plasticity in the dorsal cochlear nucleus (DCN), which is assumed to be due to axonal sprouting. Although a disrupted balance between auditory and somatosensory inputs may occur following hearing damage and may induce tinnitus, examination of this phenomenon employed a model of hearing damage that does not account for the causal relationship between these changes and tinnitus. The present study aimed to investigate changes in auditory‑somatosensory innervation and the role that axonal sprouting serves in this process by comparing results between animals with and without tinnitus. Rats were exposed to a noise‑inducing temporary threshold shift and were subsequently divided into tinnitus and non‑tinnitus groups based on the results of gap prepulse inhibition of the acoustic startle reflex. DCNs were collected from rats divided into three sub‑groups according to the number of weeks (1, 2 or 3) following noise exposure, and the protein levels of vesicular glutamate transporter 1 (VGLUT1), which is associated with auditory input to the DCN, and VGLUT2, which is in turn primarily associated with somatosensory inputs, were assessed. In addition, factors related to axonal sprouting, including growth‑associated protein 43 (GAP43), postsynaptic density protein 95, synaptophysin, α‑thalassemia/mental retardation syndrome X‑linked homolog (ATRX), growth differentiation factor 10 (GDF10), and leucine‑rich repeat and immunoglobulin domain‑containing 1, were measured by western blot analyses. Compared to the non‑tinnitus group, the tinnitus group exhibited a significant decrease in VGLUT1 at 1 week and a significant increase in VGLUT2 at 3 weeks post‑exposure. In addition, rats in the tinnitus group exhibited significant increases in GAP43 and GDF10 protein expression levels in their DCN at 3 weeks following noise exposure. Results from the present study provided further evidence that changes in the neural input distribution to the DCN may cause tinnitus and that axonal sprouting underlies these alterations.

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