Analysis of hearing loss induced by a novel environmental factor to develop a preventive method

• Project/Area Number: 16K08343
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Nagoya University
• Principal Investigator: Ohgami Nobutaka 名古屋大学, 医学系研究科, 講師 (80424919)
• Co-Investigator(Kenkyū-buntansha): 矢嶋 伊知朗 名古屋大学, 医学系研究科, 講師 (80469022) ; 飯田 真智子 愛知県心身障害者コロニー発達障害研究所, 周生期学部, 研究員 (60465515)
• Research Collaborator: KATO masashi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 難聴 / ラセン神経節 / 元素 / 神経変性 / 内耳 / マンガン / 衛生 / 環境

Outline of Final Research Achievements

There is limited information about an association between hearing loss and heavy metals. In previous studies, manganese has been shown to be detected in drinking well water. Also, exposure to manganese has been shown to cause age-related neurodegeneration. However, there is very limited information showing that oral exposure to manganese causes hearing loss in humans and mice. This study demonstrated that oral exposure to manganese via drinking water caused hearing loss with degeneration of spiral ganglion neurons in inner ears which involved decreased expression of c-Ret. This study also demonstrated the association of hearing loss and manganese levels in biological samples in humans.

Academic Significance and Societal Importance of the Research Achievements

従来、ヒトを対象にした疫学研究では病態との原因化学物質の関連は解析出来るものの、メカニズムに基づいた予知・予防方法を開発するには限界があった。マンガン（Mn）は必須微量元素であり、Mnの摂取量を制限するのは容易ではなく、全てのヒトにMnの慢性曝露による難聴リスクの可能性がある。本研究のヒトを対象にした疫学研究とマウスを対象にした実験研究の相補的アプローチにより、実験研究で得られたメカニズムをベースにした、Mnが誘発する難聴の予知・予防方法の開発につながる事が期待される。

Research Products

• [Int'l Joint Research] University of Ioannina(ギリシャ)
• [Int'l Joint Research] University of Dhaka(バングラデシュ)
• [Int'l Joint Research] ダッカ大学(バングラデシュ)
• [Journal Article] Improvement of balance in young adults by a sound component at 100?Hz in music (2018)
  • Author(s): Xu Huadong、Ohgami Nobutaka、He Tingchao、Hashimoto Kazunori、Tazaki Akira、Ohgami Kyoko、Takeda Kozue、Kato Masashi
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 16894-16894
  • DOI: 10.1038/s41598-018-35244-3
  • Peer Reviewed / Open Access
• [Journal Article] Arsenic level in toenails is associated with hearing loss in humans. (2018)
  • Author(s): Li X, Ohgami N, Yajima I, Xu H, Iiida M, Ohino R, Ninomiya H, Shen D, Ahsan N, Akhand AA, Kato M
  • Journal Title: PLoS ONE Volume: 13 Issue: 7 Pages: e0198743-e0198743
  • DOI: 10.1371/journal.pone.0198743
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Manganese in toenails is associated with hearing loss at high frequencies in humans. (2018)
  • Author(s): Ohgami N, Li X, Yajima I, Oshino R, Ohgami K, Kato Y, Ahsan N, Akhand AA, Kato M
  • Journal Title: Biomarkers Volume: 23 Issue: 6 Pages: 533-539
  • DOI: 10.1080/1354750x.2018.1458153
  • NAID: 120006536930
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Increased expression level of Hsp70 in the inner ears of mice by exposure to low frequency noise. (2018)
  • Author(s): Ninomiya H, Ohgami N, Oshino R, Kato M, Ohgami K, Li X, Shen D, Iida M, Yajima I, Angelidis CE, Adachi H, Katsuno M, Sobue G, Kato M.
  • Journal Title: Hear Res Volume: - Pages: 49-54
  • DOI: 10.1016/j.heares.2018.02.006
  • NAID: 120006517664
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Arsenic-mediated hyperpigmented skin via NF-kappa B/Endothelin1 signaling in an originally developed hairless mouse model. (2017)
  • Author(s): Yajima I, Kumasaka MY, Iida M, Osino R, Tanihata H, Al Hossain A MM, Ohgami N, Kato M.
  • Journal Title: Arch Toxicol Volume: 91 Issue: 11 Pages: 3507-16
  • DOI: 10.1007/s00204-017-1975-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Amelioration of arsenic-induced toxic effects in mice by dietary supplementation of Syzygium cumini leaf extract (2017)
  • Author(s): Barai M, Ahsan N, Paul N, Hossain K, Abdur Rashid M, Kato M, Ohgami N, Azim Akhand A.
  • Journal Title: Nagoya Journal of Medical Science Volume: 79 Issue: 2 Pages: 167-177
  • DOI: 10.18999/nagjms.79.2.167
  • NAID: 120006220084
  • ISSN: 2186-3326
  • URL: https://nagoya.repo.nii.ac.jp/records/24335
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Manganese-mediated decrease in levels of c-RET and tyrosine hydroxylase expression in vitro. (2017)
  • Author(s): Kumasaka MY, Yajima I, Ohgami N, Ninomiya H, Iida M, Li X, Oshino R, Tanihata H, Yoshinaga M, Kato M.
  • Journal Title: Neurotox Res Volume: 32 Issue: 4 Pages: 661-70
  • DOI: 10.1007/s12640-017-9783-0
  • NAID: 120006367974
  • Peer Reviewed
• [Journal Article] Oral exposure to arsenic causes hearing loss in young people aged 12-29 years and in young mice. (2017)
  • Author(s): Li X, Ohgami N, Omata Y, Yajima I, Iida M, Oshino R, Ohnuma S, Ahsan N, Akhand AA, Kato M.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 6844-6844
  • DOI: 10.1038/s41598-017-06096-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Risk assessment of neonatal exposure to low frequency noise based on balance in mice (2017)
  • Author(s): Ohgami N et al.
  • Journal Title: Front Behav Neurosci Volume: 11 Pages: 30-30
  • DOI: 10.3389/fnbeh.2017.00030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Exposure to diphtheria toxin during the juvenile period impairs both inner and outer hair cells in C57BL/6 mice (2017)
  • Author(s): Konishi H, Ohgami N, Matsushita A, Kondo Y, Aoyama Y, Kobayashi M, Nagai T, Ugawa S, Yamada K, Kato M, Kiyama H
  • Journal Title: Neuroscience Volume: 印刷中 Pages: 15-23
  • DOI: 10.1016/j.neuroscience.2017.03.028
  • NAID: 120006331816
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Impairments of Inner Ears Caused by Physical Environmental Stresses (2017)
  • Author(s): Ohgami N, Oshino R, Ninomiya H, Li X, Kato M.
  • Journal Title: Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene) Volume: 72 Issue: 1 Pages: 38-42
  • DOI: 10.1265/jjh.72.38
  • NAID: 130005306028
  • ISSN: 0021-5082, 1882-6482
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Manganese-mediated acceleration of age-related hearing loss in mice (2016)
  • Author(s): Ohgami N et al.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 36306-36306
  • DOI: 10.1038/srep36306
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Limited effectiveness of household sand filters for removal of arsenic from well water in North Vietnam. (2016)
  • Author(s): Ilmiawati C, Thang ND, Iida M, Maeda M, Ohnuma S, Yajima I, Ohgami N, Oshino R, Al Hossain MM, Ninomiya H, Kato M.
  • Journal Title: J Water Health Volume: 14(6) Pages: 1032-1040
  • NAID: 120006220428
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Reply to the commentary "To Gorelenkova Miller and Mieyal (2015): Sulfhydryl-mediated redox signaling in inflammation: role in neurodegenerative diseases" by Mieyal JJ. (2016)
  • Author(s): Kato M, Ninomiya H, Maeda M, Ilmiawati C, Al Hossain MM, Yoshinaga M, Ohgami N.
  • Journal Title: Arch Toxicol Volume: 90(6) Issue: 6 Pages: 1523-1524
  • DOI: 10.1007/s00204-016-1705-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Epidemiological analysis of the association between hearing and barium in humans (2015)
  • Author(s): Ohgami, N. Mitsumatsu, Y. Ahsan, N. Akhand, A. A. Li, X. Iida, M. Yajima, I. Naito, M. Wakai, K. Ohnuma, S. Kato, M.
  • Journal Title: J Expo Sci Environ Epidemiol Volume: - Issue: 5 Pages: 488-493
  • DOI: 10.1038/jes.2015.62
  • NAID: 120005851029
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 音楽に含まれる音成分と平衡感覚の関連 (2019)
  • Author(s): Xu Huadong、大神信孝、He Tingchao、李香、武田湖州恵、加藤昌志
  • Organizer: 第89回日本衛生学会学術総会
• [Presentation] 可聴域の騒音ストレスによるラセン神経節への影響 (2019)
  • Author(s): 大神信孝、He Tingchao、Xu Huadong、押野玲奈、李香、加藤昌志
  • Organizer: 第89回日本衛生学会学術総会
• [Presentation] 生体サンプル中の鉄レベルと聴力異常の相関解析 (2019)
  • Author(s): He Tingchao、大神信孝、李香、Xu Huadong、加藤昌志
  • Organizer: 第89回日本衛生学会学術総会
• [Presentation] 生体サンプル中のヒ素レベルと聴力異常の関連 (2019)
  • Author(s): 大神信孝、李香、Xu Huadong、He Tingchao、加藤昌志
  • Organizer: 第89回日本衛生学会学術総会
• [Presentation] 前庭障害モデルマウスを用いた前庭機能の解析 (2019)
  • Author(s): 押野玲奈、大神信孝、李香、He Tingchao、加藤昌志
  • Organizer: 第89回日本衛生学会学術総会
• [Presentation] 閉鎖空間の低周波騒音曝露による内耳のストレス関連分子の発現 (2018)
  • Author(s): 李香、大神信孝、押野玲奈、二宮裕将、加藤昌志
  • Organizer: 日本宇宙生物科学会 第32回大会
• [Presentation] 実験研究と疫学研究によるヒ素曝露の難聴リスクの解析 (2018)
  • Author(s): 李香、大神信孝、押野玲奈、加藤昌志
  • Organizer: 第29回日本微量元素学会学術集会
• [Presentation] ヒトのツメに蓄積するマンガンレベルと聴力の関連 (2018)
  • Author(s): He Tingchao、大神信孝、李香、加藤昌志
  • Organizer: 第29回日本微量元素学会学術集会
• [Presentation] マンガンの飲水曝露による聴覚系への影響 (2018)
  • Author(s): 大神信孝、李香、押野玲奈、加藤昌志
  • Organizer: 第29回日本微量元素学会学術集会
• [Presentation] 低周波騒音曝露の健康リスクを評価する実験研究 (2018)
  • Author(s): 李香、大神信孝、押野玲奈、二宮裕将、加藤昌志
  • Organizer: 第91回日本産業衛生学会
• [Presentation] 飲水投与したマンガンの聴覚系への影響 (2017)
  • Author(s): 大神信孝、李香、押野玲奈、加藤昌志
  • Organizer: 第87回日本衛生学会学術総会
  • Place of Presentation: フェニックスシーガイアリゾート（宮崎県宮崎市山崎町）
  • Year and Date: 2017-03-26
• [Presentation] マンガンの飲水投与による難聴の解析 (2017)
  • Author(s): 大神信孝、李香、押野玲奈、加藤昌志
  • Organizer: 第40回 日本神経科学大会
• [Presentation] マンガンの飲水曝露による聴覚系への影響 (2017)
  • Author(s): 大神信孝、李香、押野 玲奈、加藤昌志
  • Organizer: フォーラム2017 衛生薬学・環境トキシコロジー
• [Presentation] ヒトのツメに蓄積するマンガンレベルと聴力の関連 (2017)
  • Author(s): 大神信孝、李香、押野玲奈、矢嶋伊知朗、加藤昌志
  • Organizer: 第88回日本衛生学会学術総会
• [Presentation] 低周波騒音が平衡感覚に与える影響 (2016)
  • Author(s): 大神信孝、押野玲奈、加藤昌志
  • Organizer: フォーラム2016 衛生薬学・環境トキシコロジー
  • Place of Presentation: 昭和大学、旗の台キャンパス（東京都品川区旗の台）
  • Year and Date: 2016-09-10
• [Presentation] 低周波騒音曝露による平衡感覚異常の解析 (2016)
  • Author(s): 大神信孝、押野玲奈、二宮裕将、矢嶋伊知朗、加藤昌志
  • Organizer: 第89回日本産業衛生学会学術総会
  • Place of Presentation: 福島県文化センター、福島市音楽堂・福島市勤労青少年ホーム・福島市働く婦人の家（福島県福島市入江町）
  • Year and Date: 2016-05-24
• [Presentation] ヒ素の職業曝露と聴覚障害の可能性 (2016)
  • Author(s): 李香、大神信孝、加藤昌志
  • Organizer: 第89回日本産業衛生学会学術総会
  • Place of Presentation: 福島県文化センター、福島市音楽堂・福島市勤労青少年ホーム・福島市働く婦人の家（福島県福島市入江町）
  • Year and Date: 2016-05-24
• [Presentation] 低周波騒音曝露による平衡感覚異常の解析 (2016)
  • Author(s): 押野玲奈、大神信孝、加藤昌志
  • Organizer: 第86回日本衛生学会学術総会
  • Place of Presentation: 旭川市民文化会館（北海道旭川市7条通）
  • Year and Date: 2016-05-11
• [Presentation] 低周波騒音曝露が誘発する平衡感覚障害の解析 (2016)
  • Author(s): 大神信孝
  • Organizer: 第86回日本衛生学会学術総会 若手プロジェクトシンポジウム
  • Place of Presentation: 旭川市民文化会館（北海道旭川市7条通）
  • Year and Date: 2016-05-11
  • Invited
• [Remarks] 名古屋大学大学院 医学系研究科 環境労働衛生学
  • URL: https://www.med.nagoya-u.ac.jp/medical_J/laboratory/basic-med/social-science/environmental-health/
• [Remarks] 名古屋大学大学院 医学系研究科 環境労働衛生学 ホームページ
  • URL: https://www.med.nagoya-u.ac.jp/hygiene/
• [Patent(Industrial Property Rights)] 音発生装置 (2018)
  • Inventor(s): 加藤昌志、大神信孝、曽根三千彦、杉本賢文
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] 音発生装置 (2018)
  • Inventor(s): 加藤昌志、大神信孝
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018