Development of a preventive drug for age-related deafness targeting neural crest-related genes

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592479
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Nagoya University
• Principal Investigator: SONE MICHIHIKO 名古屋大学, 医学(系)研究科(研究院), 准教授 (30273238)
• Co-Investigator(Kenkyū-buntansha): OHGAMI Nobutaka 中部大学, 生命健康科学部, 准教授 (80424919)
• Project Period (FY): 2011 – 2013
• Keywords: 加齢性難聴 / 内耳 / ラセン神経節

Research Abstract

Preventive/cure methods for Waardenburg-Shah syndrome with congenital hearing loss has not developed yet due to congenital loss of intermediate cells (melanocytes) in inner ears. The congenital hearing loss involving neurodegeneration of spiral ganglion neurons (SGNs) in Ednrb(-/-)-mice were significantly restored by introducing an Ednrb transgene under control of the dopamine beta-hydroxylase promoter (DBH-EdnrB-Tg). The results of this study suggest Ednrb expressed in SGNs can be a novel target for a drug development of hearing losses. Meanwhile, the preventive effect of DBH-EdnrB-Tg expressed in SGNs on age-related deafness has been affected by genetic backgrounds. Further study will be needed to investigate the effect of DBH-EdnrB-Tg on age-related deafness.

Research Products

• [Journal Article] Brain deposition and neurotoxicity of manganese in adult mice exposed via the drinking water (2014)
  • Author(s): Kumasaka MY, Yajima I, Ohgami N, Naito H, Omata Y, Kato M. Commentary to Krishna et al.
  • Journal Title: Arch Toxicol Volume: (In press)
• [Journal Article] Evaluation of vascular activity in otosclerosis by laser-Doppler flowmetry : comparison with CT densitometry (2013)
  • Author(s): Sone M, Yoshida T, Otake H, Kato K, Teranishi M, Naganawa S, Nakashima T
  • Journal Title: Otol Neurotol Volume: 34 Pages: 1559-1563
• [Journal Article] Endothelin-1 gene polymorphism in sudden sensorineural hearing loss (2013)
  • Author(s): Uchida Y, Teranishi M, Nishio N, Sugiura S, Hiramatsu M, Kato K, Otake H, Yoshida T, Suzuki H, Sone M, Ando F, Shimokata H, Nakashima T
  • Journal Title: Laryngoscope Volume: 123 Pages: 59-65
• [Journal Article] Establishment of Mouse Model of MYH9 Disorders : Heterozygous R702C Mutation Provokes Macrothrombocytopenia with Leukocyte Inclusion Bodies, Renal Glomerulosclerosis and Hearing Disability (2013)
  • Author(s): Suzuki N, Kunishima S, Ikejiri M, Maruyama S, Sone M, Takagi A, Ikawa M, Okabe M, Kojima T, Saito H, Naoe T, Matsushita T
  • Journal Title: PLos One Volume: 8 Pages: e71187
• [Journal Article] Polymorphisms in genes encoding aquaporins 4 and 5 and estrogen receptorαin patients with Meniere's disease and sudden sensorineural hearing loss (2013)
  • Author(s): Nishio N, Teranishi M, Uchida Y, Sugiura S, Ando F, Shimokata H, Sone M, Otake H, Kato K, Yoshida T, Tagaya M, Hibi T, Nakashima T.
  • Journal Title: Life Sci Volume: 92 Pages: 541-546
• [Journal Article] Polymorphisms in genes involved in oxidative stress response in patients with sudden sensorineural hearing loss and Meniere's disease in a Japanese population (2013)
  • Author(s): Teranishi M, Uchida Y, Nishio N, Kato K, Otake H, Yoshida T, Suzuki H, Sone M, Sugiura S, Ando F, Shimokata H, Nakashima T
  • Journal Title: DNA Cell Biol Volume: 31 Pages: 1555-1562
• [Journal Article] Comparison of CT and MRI for evaluation of cholesteatoma with labyrinthine fistulae (2012)
  • Author(s): Sone M, Yoshida T, Naganawa S, Otake H, Kato K, Sano R, Teranishi M, Nakashima T
  • Journal Title: Laryngoscope Volume: 122 Pages: 1121-1125
• [Journal Article] Contribution of complement factor H Y402H polymorphism to sudden sensorineural hearing loss risk and possible interaction with diabetes (2012)
  • Author(s): Nishio N, Teranishi M, Uchida Y, Sugiura S, Ando F, Shimokata H, Sone M, Otake H, Kato K, Yoshida T, Tagaya M, Hibi T, Nakashima T
  • Journal Title: Gene Volume: 499 Pages: 226-230
• [Journal Article] c-Ret-mediated hearing losses (2012)
  • Author(s): Ohgami, N., Tamura, H., Ohgami, K., Iida, M., Yajima, I., Kumasaka, Y.M., Goto, Y., Sone, M., Nakashima, T., Kato, M
  • Journal Title: Int. J. Clin. Exp. Pathol Volume: 5 Pages: 23-28
• [Journal Article] Partial impairment of c-Ret at tyrosine 1062 accelerates age-related hearing loss in mice (2012)
  • Author(s): Ohgami, N., Ida-Eto, M., Sakashita, N., Sone, M., Nakashima, T., Tabuchi, K., Hoshino, T., Shimada, A., Tsuzuki, T., Yamamoto, M., Sobue, G., Jijiwa, M., Asai, N., Hara, A., Takahashi, M., Kato, M
  • Journal Title: Neurobiol. Aging Volume: 626 Pages: 25-34
• [Journal Article] Chronic exposure to low frequency noise at moderate levels causes impaired balance in mice (2012)
  • Author(s): Tamura, H., Ohgami, N., Yajima, I., Iida, M., Ohgami, K., Fujii, N., Itabe, H., Kusudo, T., Yamashita, H., Kato, M
  • Journal Title: PLoS ONE Volume: 7 Pages: e39807
• [Journal Article] Hearing impairments caused by genetic and environmental factors (2012)
  • Author(s): Ohgami, N., Iida, M., Yajima, I., Tamura, H., Ohgami, K., Kato, M
  • Journal Title: Environmental Health and Preventive Medicine Volume: 18 Pages: 10-15
• [Journal Article] Exposure to low-dose barium by drinking water causes hearing loss in mice (2012)
  • Author(s): Ohgami, N., Hori, S., Ohgami, K., Tamura, H., Tsuzuki, T., Ohnuma, S., Kato, M
  • Journal Title: NeuroToxicology Volume: 33 Pages: 1276-1283
• [Journal Article] Morphological observation in the stria vascularis in midkine and pleiotrophin knockout mice (2011)
  • Author(s): Sone M, Yoshida T, Naganawa S, Otake H, Kato K, Sano R, Teranishi M, Nakashima T
  • Journal Title: Auris Nasus Larynx Volume: 38 Pages: 41-45
• [Journal Article] Partial requirement of endothelin receptor B in spiral ganglion neurons for postnatal development of hearing (2011)
  • Author(s): Ida-Eto, M., Ohgami, N., Iida, M., Yajima, I., Kumasaka, M.Y., Takaiwa, K., Kimitsuki, T., Sone, M., Nakashima, T., Tsuzuki, T., Komune, S., Yanagisawa, M., Kato, M
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 29621-29626
• [Presentation] 腫診断における拡散強調画像の判定量的評価の有用性. (2013)
  • Author(s): 鈴木宏和、曽根三千彦、吉田忠雄、大竹宏直、加藤健、寺西正明、中島務:中耳真珠
  • Organizer: 第23回日本耳科学会総会
  • Place of Presentation: 宮崎
  • Year and Date: 20131124-26
• [Presentation] 突発性難聴における酸化ストレス関連の遺伝子多型の検討 (2013)
  • Author(s): 寺西正明、内田育恵、加藤健、大竹宏直、吉田忠雄、杉浦彩子、曽根三千彦、中島務:
  • Organizer: 第58回日本聴覚医学会総会
  • Place of Presentation: 松本
  • Year and Date: 20131017-18
• [Presentation] Partial impairment of c-Ret accelerates age-related hearing loss (2013)
  • Author(s): 大神信孝、飯田真智子、加藤昌志
  • Organizer: 第36回日本神経科学大会/ Neuroscience2013()
  • Place of Presentation: 京都
  • Year and Date: 20130620-23
• [Presentation] New Aspects on Pathophysiology and Imaging in Menieres Disease : Relationships between endolymphatic hydrops and symptoms. (2013)
  • Author(s): Sone M, Nakashima T, Yoshida T, Kato M, Teranishi M, Naganawa S
  • Organizer: The 20^<th> International Federation of Oto-Rhino-Laryngological Societies World Congress
  • Place of Presentation: Seoul, korea
  • Year and Date: 20130601-05
• [Presentation] 生活環境因子が誘発する神経変性疾患。 (2013)
  • Author(s): (4)大神信孝:
  • Organizer: 第8回Tokushima Young Investigators Conference (徳島大学医学研究科主催)
  • Year and Date: 2013-09-11
  • Invited
• [Presentation] Analysis of endothelin receptor B expressed in spiral ganglion neurons (2012)
  • Author(s): 大神信孝、飯田真智子、矢嶋伊知朗、加藤昌志:
  • Organizer: 第24回日本色素細胞学会学術大会
  • Place of Presentation: 長浜
  • Year and Date: 20121124-25
• [Presentation] 耳鳴を主訴とする症例の3テスラMRIによる内リンパ水腫評価 (2012)
  • Author(s): 吉田忠雄、大竹宏直、加藤健、下野真理子、寺西正明、曽根三千彦、中島務.
  • Organizer: 第22回日本耳科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20121004-06
• [Presentation] 内耳障害を合併するP-ANCA陽性血管炎患者の3D-FLAIR MRI画像 (2012)
  • Author(s): 加藤健、曽根三千彦、寺西正明、大竹宏直、吉田忠雄、佐野塁、中島務
  • Organizer: 第113回日本耳鼻咽喉科学会総会
  • Place of Presentation: 新潟
  • Year and Date: 20120510-13
• [Presentation] 突発性難聴における炎症性サイトカインの遺伝子多型の検討 (2011)
  • Author(s): 寺西正明、内田育恵、西尾直樹、加藤健、大竹宏直、吉田忠雄、多賀谷満彦、鈴木宏和、曽根三千彦、杉浦彩子、中島務
  • Organizer: 第21回日本耳科学会総会
  • Place of Presentation: 沖縄
  • Year and Date: 20111124-26
• [Presentation] メニエール病およびその周辺疾患における内リンパ腔MRI画像 (2011)
  • Author(s): 吉田忠雄、大竹宏直、加藤健、寺西正明、曽根三千彦、中島務.
  • Organizer: 第21回日本耳科学会総会
  • Place of Presentation: 沖縄
  • Year and Date: 20111124-26
• [Presentation] 蝸牛神経核背側核電植の一例の聴覚能の検討 (2011)
  • Author(s): 棚橋汀路、松田直子、曽根三千彦
  • Organizer: 第56回日本聴覚医学会総会
  • Place of Presentation: 博多
  • Year and Date: 20111027-28
• [Presentation] 内リンパ水腫症例における連続周波数ティンパノメトリーとMRI画像所見の比較 (2011)
  • Author(s): 加藤健、大竹宏直、吉田忠雄、寺西正明、曽根三千彦、朝日清光、中島務
  • Organizer: 第56回日本聴覚医学会総会
  • Place of Presentation: 博多
  • Year and Date: 20111027-28
• [Presentation] Endothelin receptor B in spiral ganglion neurons partially contributes to postnatal development of hearing (2011)
  • Author(s): 大神信孝、飯田真智子、田村青鳥、加藤昌志
  • Organizer: 第35回日本神経科学大会/ Neuroscience2012
  • Place of Presentation: 名古屋
  • Year and Date: 20110918-21
• [Presentation] EDN1遺伝子Lys198Asn多型に関する突発性難聴ケースコントロール研究について (2011)
  • Author(s): 内田育恵,杉浦彩子,西尾直樹,多賀谷満彦、平松真理子、吉田忠雄,大竹宏直、加藤健、寺西正明、曽根三千彦,中島務
  • Organizer: 第112回日本耳鼻咽喉科学会総会
  • Place of Presentation: 京都
  • Year and Date: 20110519-21
• [Presentation] 環境ストレスと関連する聴覚系疾患の解析 (2011)
  • Author(s): 大神信孝
  • Organizer: 第84回日本生化学会大会・シンポジウム「D-アミノ酸の生化学:飛躍する新領域」
  • Place of Presentation: 京都
  • Year and Date: 2011-09-24
• [Book] Cholesteatoma and Ear Surgery-an update. Efficacy of 3D FLAIR MRI findings in evaluating cholesteatoma with labyrinthine fistulae (2013)
  • Author(s): Sone M, Yoshida T, Nakashima T. Cholesteatoma and Ear Surgery-an update. Efficacy of 3D FLAIR MRI findings in evaluating cholesteatoma with labyrinthine fistulae.
  • Total Pages: 107-109
  • Publisher: Kugler Publications
• [Patent(Industrial Property Rights)] 聴覚障害又は小脳性運動失調症の予防・治療剤 (2012)
  • Inventor(s): 大神信孝、加藤昌志
  • Industrial Property Rights Holder: 中部大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-259456
  • Filing Date: 2012-11-28
  • Overseas