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Expression of tumor necrosis factor-α and interleukin-1β genes in the cochlea and inferior colliculus in salicylate-induced tinnitus.

Journal of neuroinflammation (2011-04-12)
Juen-Haur Hwang, Jin-Cherng Chen, Shan-Ying Yang, Ming-Fu Wang, Yin-Ching Chan
ABSTRACT

Changes 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. Forty-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. Tinnitus 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 NR2B gene 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. We 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium salicylate, tested according to Ph. Eur.
Sigma-Aldrich
Sodium salicylate, puriss. p.a., ≥99.5% (NT)
Sigma-Aldrich
Sodium salicylate, puriss. p.a., reag. Ph. Eur., 99.5-101.0% (calc. to the dried substance)
Sigma-Aldrich
Sodium salicylate, ReagentPlus®, ≥99.5%
Sigma-Aldrich
Sodium salicylate, meets USP testing specifications