New Insights on the Effect of TNF Alpha Blockade by Gene Silencing in Noise-Induced Hearing Loss.

Janaína C. Rodrigues,Karina Lezirovitz,Rubens de Brito,Gleiciele A. V. Silva,Jonatas B. do Amaral,André L. L. Bachi,Marcelo Rossi

doi:10.3390/ijms21082692

Abstract

Noise exposure represents the second most common cause of acquired sensorineural hearing loss and we observed that tumor necrosis factor α (TNFα) was involved in this context. The effect of Tnfα gene silencing on the expression profile related to the TNFα metabolic pathway in an experimental model of noise-induced hearing loss had not previously been studied. Methods: Single ears of Wistar rats were pretreated with Tnfα small interfering RNA (siRNA) by trans-tympanic administration 24 h before they were exposed to white noise (120 dBSPL for three hours). After 24 h of noise exposure, we analyzed the electrophysiological threshold and the amplitude of waves I, II, III, and IV in the auditory brain response click. In addition, qRT-PCR was performed to evaluate the TNFα metabolic pathway in the ears submitted or not to gene silencing. Results: Preservation of the electrophysiological threshold and the amplitude of waves was observed in the ears submitted to gene silencing compared to the ears not treated. Increased anti-apoptotic gene expression and decreased pro-apoptotic gene expression were found in the treated ears. Conclusion: Our results allow us to suggest that the blockade of TNFα by gene silencing was useful to prevent noise-induced hearing loss.

Highlights

Exposure to noise is one of the most common causes of acquired sensorineural hearing loss
We were able to demonstrate, for the first time, that the blockade of tumor necrosis factor α (TNFα) through gene silencing maintained the electrophysiological threshold in the ears of the rats exposed to noise as compared to the harmful alterations observed in the ears not submitted to the gene silencing
In order to evaluate the mechanism involved in the maintenance of hearing in the ears submitted to the Tnfα blockade, we analyzed several genes of TNFα metabolism pathway and found a significant up-regulation of anti-apoptotic genes, as well as a downregulation of pro-apoptotic genes in the cochlea of ears submitted to TNFα blockade by gene silencing

Summary

Introduction

Exposure to noise is one of the most common causes of acquired sensorineural hearing loss. The World Health Organization estimates that 1.1 billion young people are at risk for noise-induced hearing loss, mainly due to recreational exposure. Hearing loss and tinnitus are an important disability claim for many people [1]. In order to guarantee a correct hearing loss diagnosis, it is widely accepted that the auditory brainstem response (ABR) represents a powerful clinical tool applied during a hearing screening, threshold estimation, and site-of-lesion testing [2]. With transient stimuli (e.g., clicks or tone bursts), ABRs are commonly generated resulting in different waveforms [2] that are used to determine the occurrence or not of hearing loss and its clinical follow-up

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