Attenuation of Progressive Hearing Loss in DBA/2J Mice by Epigenetic-Modifying Reagents

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592573
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: 独立行政法人国立病院機構(東京医療センター臨床研究センター)
• Principal Investigator: MUTAI Hideki 独立行政法人国立病院機構(東京医療センター臨床研究センター), 聴覚平衡覚研究部, 研究員 (60415891)
• Co-Investigator(Kenkyū-buntansha): MIYA Fuyuki 理化学研究所, 統合生命医科学研究センター, リサーチアソシエイト (50415311)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: エピジェネティクス / 加齢性難聴 / 亜鉛トランスポーター / 緑茶カテキン / EGCG

Outline of Final Research Achievements

Hearing loss can be caused by a combination of multiple environmental and genetic factors. In this study, we investigated whether epigenetic regulatory pathways could modulate a mouse model of progressive hearing loss.
Subcutaneous treatment of DBA/2J mice with a combination of epigenetic modifying reagents, methionine and valproic acid (M+V) significantly reduced the decline of hearing. Microarray analyses and subsequent quantitative RT-PCR and immunohistochemistry demonstrated up-regulation of a zinc importer, Zip4 in the cochlear tissues in association with attenuation of progressive hearing loss. Treatement of DBA mice with EGCG, a major green tea catechin with Zip4-inducing activity resulted in attenuation of hearing decline. This study suggests that epigenetic pathways can modify auditory function and demonstrates that zinc intake in the cochlea via Zip4 mediates the maintenance of mammalian hearing.

Free Research Field

耳科学　分子生物学