Investigation of roles of nitric oxide in age-related cen aninemal hearing loss n Ring mock-out mice and its clinical application

• Project/Area Number: 17591784
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Nagoya University
• Principal Investigator: TERANISHI Masaaki Nagoya University, Granduate School of Medicine, Associate Professor (20335037)
• Co-Investigator(Kenkyū-buntansha): NAKASHIMA Tsutomu Nagoya University, Granduate School of Medicine, Professor (30180277)
• Project Period (FY): 2005 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,680,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥180,000); Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
• Keywords: inner ear / aging / nitric oxide(NO) / oxidative stress / nitric oxide (NO) / 蝸牛 / Akt / PKB / 加齡

Research Abstract

Age-related hearing loss decreases quality of life of elderly people. Prevention and treatment of age-related hearing loss are important and urgent tasks. We investigated auditory function by auditory brain stem (ABR) responses, using C57BIJ8 mice as an experimental model of age-related hearing loss. We observed changes of nitric oxide and free-radical related substances in the inner ear using an immunohistcehemical method under a light microscope. ABE demonstrated that hearing levels of 7-8 month-old mice and 12 month-old mice were worse than those of 7 week-old mice. Hearing levels of 12 month-old mice were worse than those of 7-8 month-old mice. Expressions of inducible type NO synthase (NOS) and nitrotyrosine, a marker of peroxynitrite which is a strong radical, were enhanced in Corti organ, spiral ganglion cells and lateral wall of cochleae in 7-8 month-old mice, compared with 12 month-old mice. These results suggest that NO and oxidative stress is associated with cell damage and cell death of cochleae of aged mice. Hearing levels of mice with NOS gene deletion tend to be worse, as they grow old, compared with wild type, suggesting that NOS functions in a protective way for age-related heaving Ices. Active firm of Alit (phospho-Akt) influences NO production by activation of endothelial NOS (eNOS). Expression of Akt was observed in cochlea and vestibule in our experiments. This suggested that phospho-Akt is associated with survival signal in the inner eat.

Research Products

• [Journal Article] Otoacoustic emissions, ear fullness and tinnitus in the recovery course of sudden deafness (2008)
  • Author(s): Ishida IM, Sugiura M, Teranishi M., Katayama N, Nakashima T
  • Journal Title: Auris Nasus Larynx 35 Pages: 41-46
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Otoacoustic emissions, ear fullness and tinnitus in the recovery course of sudden deafness (2008)
  • Author(s): Ishida, IM, Sugiura, M, Teranishi, M., Katayama, N, Nakashima, T
  • Journal Title: Auris Nasus Larynx 35 Pages: 41-46
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Visualization of endolymphatic hydrops in patients with Meniere's disease (2007)
  • Author(s): Nakashima T, Naganawa S, Sugiura M, Teranishi M, et. al.
  • Journal Title: Laryngoscope 117 Pages: 415-420
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Thirty-year trends in sudden deafness from four nationwide epidemiol ogical surveys in Japan (2007)
  • Author(s): Teranishi M, Katayama N, Uchida Y, Tominaga M, Nakashima T
  • Journal Title: Acta Otolaryngol. 127 Pages: 1259-1265
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Cochlear modiolus and lateral semicircular canal in sudden deafness (2007)
  • Author(s): Ishida IM, Sugiura M, Naganawa S, Teranishi M., Nakashima T
  • Journal Title: Acta Otolaryngol. 127 Pages: 1157-1161
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Vestibular aqueduct in sudden sensorineural hearing loss (2007)
  • Author(s): Sugiura M, Naganawa S, Ishida IM, Teranishi M., Nakata S, et. al.
  • Journal Title: J Laryngol Otol (in press)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Visualization of endolymphatic hydrops in patients with Meniere's disease (2007)
  • Author(s): Nakashima, T., Naganawam, S., Sugiura, M., Teranishi, M., Sone, M., Hayashi, H., Nakata, S., Katayama, N., Ishida, IM
  • Journal Title: Laryngoscope 117 Pages: 415-420
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Thirty-year trends in sudden deafness from four nationwide epidemiological surveys in Japan (2007)
  • Author(s): Teranishi, M., Katayama, N., Uchida, Y., Tominaga, M., Nakashima, T
  • Journal Title: Acta Otolaryngol 127 Pages: 1259-1265
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cochlear modiolus and lateral semicircular canal in sudden deafness (2007)
  • Author(s): Ishida, IM, Sugiura, M, Naganawa, S, Teranishi, M., Nakashima, T
  • Journal Title: Acta Otolaryngol 127 Pages: 1157-1161
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Vestibular aqueduct in sudden sensorineural hearing loss (2007)
  • Author(s): Sugiura, M., Naganawa, S., Ishida, IM., Teranishi, M., Nakata, S., Yoshida, T., Nakashima, T
  • Journal Title: J Laryngol Otol (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Visualization of endolymphatic hydrops in patients with Meniere's disease (2007)
  • Author(s): Nakashima T, Naganawa S, Sugiura M, Teranishi M, Sone M, et. al.
  • Journal Title: Laryngoscope 117 Pages: 415-420
  • Peer Reviewed
• [Journal Article] Thirty-year trends in sudden deafness from four nationwide epidemiological surveys in Japan (2007)
  • Author(s): Teranishi M, Katayama N, Uchida Y, Tominaga M, Nakashima T
  • Journal Title: Acta Otolaryngol. 127 Pages: 1259-1265
  • Peer Reviewed
• [Journal Article] Cochlear modiolus and lateral semicircular canal in sudden deafness (2007)
  • Author(s): Ishida IM, Sugiura M, Naganawa S, Teranishi M., Nakashima T
  • Journal Title: Acta Otolaryngol 127 Pages: 1157-1161
  • Peer Reviewed
• [Journal Article] 内耳性難聴における血液迷路関門の破綻症例について (2007)
  • Author(s): 吉田忠雄、杉浦 真、寺西正明、中田誠一、中島 務
  • Journal Title: Audiology Japan 50 Pages: 157-162
  • NAID: 10021299497
  • Peer Reviewed
• [Journal Article] 錐体部真珠腫術後の開放露出硬膜部の治癒経過 (2007)
  • Author(s): 曾根三千彦、寺西正明、中島 務
  • Journal Title: Otology Japan 17 Pages: 139-142
  • Peer Reviewed
• [Journal Article] 全国疫学調査結果を用いた突発性難聴年間受療患者数の地域別検討 (2007)
  • Author(s): 寺西正明、片由直美、内田育恵、戸田潤二、中島 務、喜多村 健
  • Journal Title: Otology Japan 17 Pages: 621-626
  • NAID: 10021297695
  • Peer Reviewed
• [Journal Article] Visualization of Endolymphatic Hydrops in Patients With Meniere's Disease. (2007)
  • Author(s): Nakashima T., Naganawa S., Sugiura M., Teranishi M., Sone M., Hayashi H., Nakata S., Katayama N., Ishida I.M.
  • Journal Title: Laryngoscope 117 Pages: 415-420
• [Journal Article] Response of cochlear blood flow to prostaglandin E1 applied topically to the round window. (2006)
  • Author(s): Tominaga M., Yamamoto H., Sone M., Teranishi M., Nakashima T.
  • Journal Title: Acta Otolaryngol. 126 Pages: 232-236
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Blood flow to the promontory in cochlear otosclerosis. (2006)
  • Author(s): Nakashima T., Sone M., Fujii H., Teranishi M., Yamamoto H., Otake H., Sugiura M., et. al.
  • Journal Title: Clin Otolaryngol. 3 Pages: 110-115
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Inner ear hemorrhage in systemic lupus erythematosus. (2006)
  • Author(s): Sugiura M., Naganawa S., Teranishi M., Sato E., Kojima S., Nakashima T.
  • Journal Title: Laryngoscope 116 Pages: 826-828
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Distribution of pendrin in the organ of Corti of mice observed by electron immunomicroscopy. (2006)
  • Author(s): Yoshino T., Sato E., Nakashima T., Teranishi M., Yamamoto H., Otake H., Mizuno T.
  • Journal Title: Eur Arch Otorhinolaryngol. 263 Pages: 699-704
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging findings in patients with sudden sensorineural hearing loss. (2006)
  • Author(s): Sugiura M., Naganawa S., Teranishi M., Nakashima T.
  • Journal Title: Laryngoscope 116 Pages: 1451-1454
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Response of cochlear blood flow to prostaglandin El applied topically to the round window (2006)
  • Author(s): Tominaga, M., Yamamoto, H., Sone, M., Teranishi, M., Nakashima, T
  • Journal Title: Acta Otolaryngol 126 Pages: 232-236
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Blood flow to the promontory in cochlear otosclerosis (2006)
  • Author(s): Nakashima, T., Sone, M., Fujii, H., Teranishi, M., Yamamoto, H., Otake, H., Sugiura, M., Naganawa, S
  • Journal Title: Clin Otolaryngol 3 Pages: 110-115
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inner ear hemorrhage in systemic lupus erythematosus (2006)
  • Author(s): Sugiura, M., Naganawa, S., Teranishi, M., Sato, E., Kojima, S., Nakashima, T
  • Journal Title: Laryngoscope 116 Pages: 826-828
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Distribution of pendrin in the organ of Corti of mice observed by electron immunomicroscopy (2006)
  • Author(s): Yoshino, T., Sato, E., Nakashima, T., Teranishi, M., Yamamoto, H., Otake, H., Mizuno, T
  • Journal Title: Eur Arch Otorhinolaryngol 263 Pages: 699-704
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging fmdings in patients with sudden sensorineural hearing loss (2006)
  • Author(s): Sugiura, M., Naganawa, S., Teranishi, M., Nakashima, T
  • Journal Title: Laryngoscope 116 Pages: 1451-1454
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Response of cochlear blood flow to prostaglandin E1 applied topically to the round window (2006)
  • Author(s): Tominaga M, Yamamoto H, Sone M, Teranishi M, Nakashima T
  • Journal Title: Acta Oto-Laryngologica 126(3) Pages: 232-236
• [Journal Article] 救急疾患の診断と治療 突発性難聴 (2006)
  • Author(s): 寺西正明, 中島 務
  • Journal Title: JOHNS 22(3) Pages: 340-344
• [Journal Article] 加齢による難聴に対する蝸牛の酸化ストレスおよびNOの関与 (2006)
  • Author(s): 寺西正明, 中島 務
  • Journal Title: 耳鼻咽喉科・免疫アレルギー 24巻2号(掲載予定)(未定)
• [Journal Article] Case report : Inner ear hemorrhage in systemic Lupus erythematosus (2006)
  • Author(s): Sugiura M, Naganawa S, Teranishi M, Sato E, Kojima S, Nakashima T
  • Journal Title: Laryngoscope (in press)
• [Journal Article] Activation of caspase-3 is associated with oxidative stress in the hydropic guinea pig cochlea. (2005)
  • Author(s): Labbe D., Teranishi M., Hess A., Bloch W., Michel O.
  • Journal Title: Hear. Res. 202 Pages: 21-27
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Expression of cyclic GMP-dependent protein kinase-I in the mouse in ner ear. (2005)
  • Author(s): Teranishi M., Labbe D., Bloch W., Michel O., Nakashima T.
  • Journal Title: Proceedings of the 5th International Symposium on Meniere's Disease & Inner Ear Homeostasis Disorders Pages: 271-272
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Activation of caspase-3 is associated with oxidative stress in the hydropic guinea pig cochlea (2005)
  • Author(s): Labbe, D., Teranishi, M., Hess, A., Bloch, W., Michel, O
  • Journal Title: Hear. Res 202 Pages: 21-27
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of cyclic GMP-dependent protein kinase-I in the mouse inner ear (2005)
  • Author(s): Teranisi, M., Labbe, D., Bloch, W., Michel, O., Nakashima, T
  • Journal Title: Proceedings of the 5thInternational Symposium on Meniere's Disease & Inner Ear Homeostasis Disorders Pages: 271-272
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of cyclic GMP-dependent protein kinase-I in the mouse inner ear (2005)
  • Author(s): Teranishi M, Labbe D, Bloch W, Michel O, Nakashima T
  • Journal Title: Meniere's Disease & Inner Ear Homeostasis Disorders Pages: 271-272
• [Journal Article] 突発性難聴の治療と効果判定 (2005)
  • Author(s): 中島 務, 寺西正明
  • Journal Title: ENTONI 54 Pages: 20-27
• [Presentation] Visualization of endolymphatic hydrops in patients with inner ear diseases (2007)
  • Author(s): Teranishi M., Hayashi H, Sugiura M, Katayama N, et. al.
  • Organizer: 9th Japan-Taiwan Conference in Oto-Rhino-Laryngolgy, Head and Neck Surgery
  • Place of Presentation: Sendai(Japan)
  • Year and Date: 2007-11-10
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Visualization of endolymphatic hydrops in patients with inner ear diseases (2007)
  • Author(s): Teranishi, M., Hayashi, H, Sugiura, M., Katayama, N., Nakata, S., Sone, M., Naganawa, S., Nakashima, T
  • Organizer: 9th Japan-Taiwan Conference in Oto-Rhino-Laryngolgy, Head and Neck Surgery
  • Place of Presentation: Sendai (Japan)
  • Year and Date: 2007-11-10
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Intratympanic steroid application for idiopathic sudden sensorineural hearing loss as a salvage treatment (2007)
  • Author(s): Teranishi M., Yoshida T, Hayashi H, Iwata T, et. al.
  • Organizer: 26th Politzer Society Meeting
  • Place of Presentation: Cleveland(USA)
  • Year and Date: 2007-10-16
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Intratympanic steroid application for idiopathic sudden sensorineural hearing loss as a salvage treatment (2007)
  • Author(s): Teranishi, M., Yoshida, T., Hayashi, H., Iwata, T., Katayama, N., Nakata, S., Nakashima, T
  • Organizer: 26th Politzer Society Meeting
  • Place of Presentation: Cleveland (USA)
  • Year and Date: 2007-10-16
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Endolymphatic and perilymphatic space imaging in patients with inner ear diseases (2007)
  • Author(s): Nakashima T., Teranishi M., Sugiura M., Sone M., Hayashi H., Naganawa S.
  • Organizer: 26th Politzer Society Meeting
  • Place of Presentation: Cleveland(USA)
  • Year and Date: 2007-10-14
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Endolymphatic and perilymphatic space imaging in patients with inner ear diseases (2007)
  • Author(s): Nakashima, T., Teranishi, M., Sugiura, M., Sone, M., Hayashi, H., Naganawa, S
  • Organizer: 26th Politzer Society Meeting
  • Place of Presentation: Cleveland (USA)
  • Year and Date: 2007-10-14
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 急性低音障害型感音難聴の難治例における内リンパ腔の画像評価 (2007)
  • Author(s): 寺西正明、吉田忠雄、杉浦 真、片山直美、中田誠一、曾根三千彦、中島 務
  • Organizer: 第52回日本聴覚医学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-10-04
• [Presentation] ゲンタマイシン鼓室内注入後に急に聴力低下をきたしたメニエール病症例 (2007)
  • Author(s): 杉浦 真、寺西正明、中田誠一、三澤逸人、中島 務
  • Organizer: 第52回日本聴覚医学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-10-04
• [Presentation] 突発性難聴症例の内耳病態評価 3D-FLAIR MRIを用いて (2007)
  • Author(s): 吉田忠雄、杉浦 真、寺西正明、中田誠一、曾根三千彦、中島 務
  • Organizer: 第52回日本聴覚医学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-10-04
• [Presentation] 住民検診における「耳の聞こえ」「耳鳴」に及ぼす要因の検討 (2007)
  • Author(s): 片山直美、寺西正明、中島 務
  • Organizer: 第52回日本聴覚医学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-10-04
• [Presentation] 内リンパ水腫の画像診断 (2007)
  • Author(s): 寺西正明、杉浦 真、林 秀雄、 吉田忠雄、山本磨早子、片山直美、中田誠一、曾根三千彦、中島 務
  • Organizer: 第55回中部地方会連合会
  • Place of Presentation: 福井
  • Year and Date: 2007-07-21
• [Presentation] 3D-FLAIR MRIによる突発性難聴の内耳病態評価 (2007)
  • Author(s): 吉田忠雄、杉浦 真、寺西正明、中田誠一、曾根三千彦、中島 務
  • Organizer: 第108回日本耳鼻咽喉科学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2007-05-19
• [Presentation] MRIによる内リンパ水腫の描出 鼓室内ガドリニウム注入後の3D-FLAIRをもちいて (2007)
  • Author(s): 杉浦 真、吉田忠雄、吉野麻子、林 秀雄、寺西正明、中田誠一、曾根三千彦、中島 務
  • Organizer: 第108回日本耳鼻咽喉科学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2007-05-19
• [Presentation] Expression of caveolin-1 in the vestibulocochlear system of mice (2006)
  • Author(s): Teranishi M., Labbe D., Michel O., Bloch W., Nakashima T.
  • Organizer: 29th Annual Mid Winter Research Meeting of the Association for Research in Otorhinolaryngology
  • Place of Presentation: Baltimore(USA)
  • Year and Date: 2006-02-08
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Cochlear blood flow during occlusion and reperfusion of the anterior inferior cerebellar artery-Effects of topical application of dexamethasone to the round window (2006)
  • Author(s): Otake H., Yamamoto H., Teranishi M., Sone M., et. al.
  • Organizer: 29th Annual Mid Winter Research Meeting of the Association for Research in Otorhinolaryngology
  • Place of Presentation: Baltimore(USA)
  • Year and Date: 2006-02-08
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Expression of caveolin-1 in the vestibulocochlear system of mice (2006)
  • Author(s): Teranishi, M., Labbe, D., Michel, O., Bloch, W., Nakashima, T
  • Organizer: 29th Annual MidWinter Research Meeting of the Association for Research in Otorhinolaryngology
  • Place of Presentation: Baltimore (USA)
  • Year and Date: 2006-02-08
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Cochlear blood flow during occlusion and reperfusion of the anterior inferior cerebellar artery- Effects of topical application of dexamethasone to the round window (2006)
  • Author(s): Otake, H., Yamamoto, H., Teranishi, M., Sone, M., Nakashima, T
  • Organizer: 29th Annual MidWinter Research Meeting of the Association for Research in Otorhinolaryngology
  • Place of Presentation: Baltimore (USA)
  • Year and Date: 2006-02-08
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Comparative study on sudden deafness by four nationwide epidemiolo gical surveys in Japan (2005)
  • Author(s): Teranishi M., Katayama N, Ishida I. M., Uchida Y., Tominaga M., et. al.
  • Organizer: 25th Politzer Society Meeting
  • Place of Presentation: Seoul(Korea)
  • Year and Date: 2005-10-07
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Cochlear blood flow in patients with sensorineural hearing loss (2005)
  • Author(s): Nakashima T., Sone M., Teranishi M., Yamamoto H., Sugiura M., Otake H., Fujii H.
  • Organizer: 25th Politzer Society Meeting
  • Place of Presentation: Seoul(Korea)
  • Year and Date: 2005-10-07
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Comparative study on sudden deafness by four nationwide epidemiological surveys in Japan (2005)
  • Author(s): Teranishi, M., Katayama, N., Ishida, I.M., Uchida, Y., Tominaga, M., Toda, J., Nakashima, T
  • Organizer: 25thPolitzer Society Meeting
  • Place of Presentation: Seoul (Korea)
  • Year and Date: 2005-10-07
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Cochlear blood flow in patients with sensorineural hearing loss (2005)
  • Author(s): Nakashima, T., Sone, M., Teranishi, M., Yamamoto, H., Sugiura, M., Otake, H., Fujii, H
  • Organizer: 25th Politzer Society Meeting
  • Place of Presentation: Seoul (Korea)
  • Year and Date: 2005-10-07
  • Description: 「研究成果報告書概要(欧文)」より