Dynamic changes of the transcriptome in the cochlea with acute sensorineural hearing loss

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K11181
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Okayama University
• Principal Investigator: Maeda Yukihide 岡山大学, 大学病院, 講師 (00423327)
• Co-Investigator(Kenkyū-buntansha): 假谷 伸 岡山大学, 医歯薬学総合研究科, 准教授 (10274226) ; 菅谷 明子 岡山大学, 大学病院, 助教 (20600224)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 蝸牛 / 急性音響性障害 / 次世代シークエンサー / RNA-seq / DNAマイクロアレイ / リアルタイムRT-PCR / 免疫機能 / 炎症機能

Outline of Final Research Achievements

In this study gene expressions were comprehensively analyzed in mice cochleae following intense noise exposure by means of next generation sequencing (RNA-seq), DNA microarray, and realtime RT-PCR. The intense noise exposure caused sensorineural hearing loss in mice. It was clarified that a number of inflammation- and immunity- related genes was differentially expressed in the cochlea at 12h following acoustic trauma as compared to the control cochlea without acoustic trauma. The differentially expressed genes in the noise-exposed cochlea included dozens of immunity-related cytokines and their receptors, such as Ccl12、Ccl2、Ccl4、Ccl7、Cxcl1、Cxcl10、Ptgs2（upregulated genes）and Ccr7、Cxcr2, Kng1、Ltb、Tnfsf14（downregulated genes）.　Intraperitoneal dexamethasone was administered immediately after the noise exposure and further modulated expressions of the inflammation- ad immunity-related genes in the cochlea at 12 hours following acoustic trauma, but not at 24 hours and 48 hours.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

急性感音難聴は、耳鼻咽喉科の日常臨床で比較的頻繁にみられ、かつ難治性の病態である。その治療では発症早期にステロイドが用いられることが多いが、その病態や作用機序の多くは不明である。当研究では、強大音響に暴露することにより難聴を発症したマウスの内耳で、全ゲノムを対象とした遺伝子発現解析を行った。その結果、難聴発症早期の内耳では炎症・免疫機能に関係する遺伝子群が多く変動することがわかった。当研究の成果は急性感音難聴の適切な治療法を開発する上で役立つ。