Abstract

BackgroundChanges in the gene expressions for tumor necrosis factor-α (TNF-α) and/or interleukin-1β (IL-1β) during tinnitus have not been previously reported. We evaluated tinnitus and mRNA expression levels of TNF-α, IL-1β, and N-methyl D-aspartate receptor subunit 2B (NR2B) genes in cochlea and inferior colliculus (IC) of mice after intraperitoneal injections of salicylate.MethodsForty-eight 3-month-old male SAMP8 mice were randomly and equally divided into two groups: salicylate-treated and saline-treated. All mice were trained to perform an active avoidance task for 5 days. Once conditioned, an active avoidance task was performed 2 hours after daily intraperitoneal injections of saline, either alone or containing 300 mg/kg sodium salicylate. Total numbers of times (tinnitus score) the mice climbed during the inter-trial silent period for 10 trials were recorded daily for 4 days (days 7 to 10), and then mice were euthanized for determination of mRNA expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC at day 10.ResultsTinnitus scores increased in response to daily salicylate treatments. The mRNA expression levels of TNF-α increased significantly for the salicylate-treated group compared to the control group in both cochlea (1.89 ± 0.22 vs. 0.87 ± 0.07, P < 0.0001) and IC (2.12 ± 0.23 vs. 1.73 ± 0.22, p = 0.0040). mRNA expression levels for the IL-1β gene also increased significantly in the salicylate group compared to the control group in both cochlea (3.50 ± 1.05 vs. 2.80 ± 0.28, p < 0.0001) and IC (2.94 ± 0.51 versus 1.24 ± 0.52, p = 0.0013). Linear regression analysis revealed a significant positive association between tinnitus scores and expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC. In addition, expression levels of the TNF-α gene were positively correlated with those of the NR2Bgene in both cochlea and IC; whereas, the expression levels of the IL-1β gene was positively correlated with that of the NR2B gene in IC, but not in cochlea.ConclusionWe conclude that salicylate treatment resulting in tinnitus augments expression of the TNF-α and IL-1β genes in cochlea and IC of mice, and we suggest that these proinflammatory cytokines might lead to tinnitus directly or via modulating the NMDA receptor.

Highlights

  • Changes in the gene expressions for tumor necrosis factor-a (TNF-a) and/or interleukin-1b (IL-1b) during tinnitus have not been previously reported

  • Tinnitus scores, defined as the total number of times the mice climbed to the safe area during the inter-trial silent period of 1 minute for 10 trials, increased between day 1 and day 4 of intraperitoneal injections for salicylate-treated mice but did not increase in the control group

  • The mean tinnitus score at day 4 was 0.5 ± 0.5 for the control group and was 8.0 ± 1.5 for the salicylate group

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Summary

Introduction

Changes in the gene expressions for tumor necrosis factor-a (TNF-a) and/or interleukin-1b (IL-1b) during tinnitus have not been previously reported. We evaluated tinnitus and mRNA expression levels of TNF-a, IL1b, and N-methyl D-aspartate receptor subunit 2B (NR2B) genes in cochlea and inferior colliculus (IC) of mice after intraperitoneal injections of salicylate. Tinnitus is distinguishable from auditory hallucinations, which involve hearing one or more talking voices. Tinnitus-related changes in gene expression have been recently reported. Jia and Qin [4] have reported that expression of c-fos and NR2A increases in auditory cortexes of rats that experience tinnitus after salicylate injection. We have found that mRNA expression levels for COX-2 decrease slightly, whereas expression levels of NR2B increase moderately in cochlea and midbrain of salicylate-treated, senescence accelerated prone mice substrain 8 (SAMP8 mice) [5]

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