The role of thyroid hormone function in different brain regions during brain development and the development of novel methods to measure the effect of environmental chemicals.

• Project/Area Number: 26340036
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kanagawa University of Human Services (2015-2016); Gunma University (2014)
• Principal Investigator: IWASAKI Toshiharu 神奈川県立保健福祉大学, 保健福祉学部, 教授 (80375576)
• Co-Investigator(Kenkyū-buntansha): 鯉淵 典之 群馬大学, 大学院医学系研究科, 教授 (80234681)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 甲状腺ホルモン / 環境化学物質 / 脳発達 / コファクター / 初代培養 / 遺伝子改変動物 / cofactor

Outline of Final Research Achievements

To study the effect of thyroid hormone (TH) and its receptor (TR) during brain development, we analyzed the hypo-thyroid model animals including transgenic mice expressing a mutant human TR specifically in cerebellar Purkinje cells. These mice showed abnormal cerebellar morphogenesis and motor coordination defect.
We also investigated the effect of environmental chemicals during brain development including developmental origins of health and disease (DOHaD). We analyzed not only environmental chemicals but also soy bean polyphenols and gadolinium-based contrast agents. We found that each chemical showed different effects through different pathways to the brain function. We found that PFOS may disrupt dendrite arbolization through a system other than genomic pathway.

Research Products

• [Int'l Joint Research] Harvard Medical School/The University of Chicago(米国)
• [Int'l Joint Research] Universitas Padjadjaran(インドネシア)
• [Journal Article] Effects of gadolinium-based contrast agents on thyroid hormone receptor action and thyroid hormone-induced cerebellar Purkinje cell morphogenesis. (2016)
  • Author(s): Ariyani W, Iwasaki T, Miyazaki W, Khongorzul E, Nakajima T, Kameo S, Koyama H, Tsushima Y, Koibuchi N.
  • Journal Title: Front Endocrinol Volume: 7 Pages: 1-11
  • DOI: 10.3389/fendo.2016.00115
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The change in thyroid hormone signaling by altered training intensity in male rat skeletal muscle (2016)
  • Author(s): Lesmana R, Iwasaki T, Iizuka Y, Amano I, Shimokawa N, Koibuchi N.
  • Journal Title: Endocrine Journal Volume: 63 Issue: 8 Pages: 727-738
  • DOI: 10.1507/endocrj.EJ16-0126
  • NAID: 130005261397
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Aberrant cerebellar development in mice lacking dual oxidase maturation factors. (2016)
  • Author(s): Amano I, Takatsuru Y, Toya S, Haijima A, Iwasaki T, Grasberger H, Refetoff S, Koibuchi N.
  • Journal Title: Thyroid Volume: 26 Issue: 5 Pages: 741-752
  • DOI: 10.1089/thy.2015.0034
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Aberrant cerebellar development of transgenic mice expressing dominant-negative thyroid hormone receptor in cerebellar purkinje cells. (2015)
  • Author(s): Yu L, Iwasaki T, Xu M, Lesmana R, Xiong Y, Shimokawa N, Chin WW, Koibuchi N.
  • Journal Title: Endocrinology Volume: 156 Issue: 4 Pages: 1565-1576
  • DOI: 10.1210/en.2014-1079
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Possible involvement of IGF-1 signaling on compensatory growth of the infraspinatus muscle induced by the supraspinatus tendon detachment of rat shoulder (2014)
  • Author(s): Ichinose T, Lesmana R, Yamamoto A, Kobayashi T, Shitara H, Shimoyama D, Takatsuru Y, Iwasaki T, Shimokawa N, Takagishi K, Koibuchi N
  • Journal Title: Physiological Rep Volume: 2 Issue: 1 Pages: 1-10
  • DOI: 10.1002/phy2.197
  • Peer Reviewed / Open Access
• [Journal Article] Altered cerebellum development and dopamine distribution in a rat genetic model with congenital hypothyroidism. (2014)
  • Author(s): Shimokawa N, Yousefi B, Morioka S, Yamaguchi S, Ohsawa A, Hayashi H, Azuma A, Mizuno H, Kasagi M, Masuda H, Jingu H, Furudate SI, Haijima A, Takatsuru Y, Iwasaki T, Umezu M, Koibuchi N.
  • Journal Title: J Neuroendocrinol. Volume: 26 Issue: 3 Pages: 164-175
  • DOI: 10.1111/jne.12135
  • Peer Reviewed / Open Access
• [Journal Article] Spikar, a novel drebrin-binding protein, regulates the formation and stabilization of dendritic spines. (2014)
  • Author(s): Yamazaki H, Kojima N, Kato K, Hirose E, Iwasaki T, Mizui T, Takahashi H, Hanamura K, Roppongi RT, Koibuchi N, Sekino Y, Mori N, Shirao T.
  • Journal Title: J Neurochem. Volume: 128 Issue: 4 Pages: 507-522
  • DOI: 10.1111/jnc.12486
  • Peer Reviewed / Open Access
• [Presentation] Early life exposure of perfluorooctane sulfonate causes cerebellar dysfunction possibly through suppression of iodothyronin deiodenase 2 activity. (2017)
  • Author(s): Iwasaki T, Kuribara H, Haijima A, Miyasaka Y, Araki O, Lu Yu, Amano I, Takatsuru Y, Shimokawa N, Murakami M, Koibuchi N.
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: 浜松
  • Year and Date: 2017-03-28
• [Presentation] 甲状腺ホルモン受容体機能を活性化する環境化学物質の解析 (2016)
  • Author(s): 岩崎俊晴、原口瑞樹、大澤 祥、宮坂祐平、鯉淵典之
  • Organizer: 環境ホルモン学会第19回研究発表会
  • Place of Presentation: つくば
  • Year and Date: 2016-12-08
• [Presentation] Function of Thyroid Hormone Receptor in Cerebellar Development ~ Study of Transgenic Mice Expressing Mutant TR in Cerebellar Purkinje Cells (2016)
  • Author(s): Iwasaki T
  • Organizer: Bandung International Biomolecular Medicine Conference (BIBMC)
  • Place of Presentation: Bandung, Indonesia
  • Year and Date: 2016-10-04
  • Int'l Joint Research / Invited
• [Presentation] Augmentation of thyroid horrnone receptor-mediated transcription and thyroid hormone-induced cerebellar morphogenesis by genistein and daidzein. (2016)
  • Author(s): Ariyani Winda、岩崎俊晴、Lu Yu，天野出月、宮崎航、高鶴裕介，鯉淵典之
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2016-03-22
• [Presentation] Perfluorooctane Sulfonate (PFOS)の早期曝露による甲状腺ホルモン脱ヨード化酵素活性の抑制による小脳機能の抑制 (2016)
  • Author(s): 岩崎俊晴，蓜島旭，宮坂勇平，荒木修，栗原光累，Lu Yu，天野出月，高鶴裕介，下川哲昭，鯉淵典之
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2016-03-22
• [Presentation] 授乳期の異なる時期のパーフルオロオクタンスルホン酸曝露による発達神経毒性影響の比較 (2016)
  • Author(s): 蓜島旭，天野出月，高鶴裕介，岩崎俊晴，鯉淵典之
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2016-03-22
• [Presentation] EID1はUCP-1の発現を介して脂肪の蓄積を抑制する (2016)
  • Author(s): 佐藤友彦，岩崎俊晴，下川哲昭，鯉淵典之
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2016-03-22
• [Presentation] 天然植物イソフラボンゲニスタインによる脳発達に対する影響 (2015)
  • Author(s): 岩崎俊晴，Winda Ariyani，栗原光累，Lu Yu，宮崎航，蓜島旭，鯉淵典之
  • Organizer: 環境ホルモン学会第18回研究発表会
  • Place of Presentation: 栃木
  • Year and Date: 2015-12-10
• [Presentation] Perfluorooctane sulfate（PFOS）による甲状腺ホルモン系に対する新たな機序による脳発達への影響 (2015)
  • Author(s): 栗原光累，岩崎俊晴，蓜島旭，宮坂勇平，荒木修，Lu Yu，高鶴裕介，下川哲昭，村上正巳，鯉淵典之
  • Organizer: 環境ホルモン学会第18回研究発表会
  • Place of Presentation: 栃木
  • Year and Date: 2015-12-10
• [Presentation] 授乳期の異なる時期のパーフルオロオクタンスルホン酸（PFOS）曝露が成熟後仔マウスの協調運動機能および学習機能へ及ぼす影響の比較 (2015)
  • Author(s): 蓜島旭，天野出月，高鶴裕介，岩崎俊晴，鯉淵典之
  • Organizer: 環境ホルモン学会第18回研究発表会
  • Place of Presentation: 栃木
  • Year and Date: 2015-12-10
• [Presentation] 脳発達期に発現するコファクターの解析 (2015)
  • Author(s): 岩崎俊晴，鯉淵典之
  • Organizer: 第58回日本甲状腺学会学術集会
  • Place of Presentation: 福島
  • Year and Date: 2015-11-05
  • Invited
• [Presentation] Altered cerebellar development of mice deficient in dual oxidese maturation factors. (2015)
  • Author(s): Amano I, Takatsuru Y, Toya S, Haijima A, Iwasaki T, Grasberger H, Refetoff S, Koibuchi N.
  • Organizer: 15th International Thyroid Congress.
  • Place of Presentation: Orlando, FL USA.
  • Year and Date: 2015-10-18
  • Int'l Joint Research / Invited
• [Presentation] 脳発達と核内ホルモン受容体研究 (2015)
  • Author(s): 岩崎俊晴
  • Organizer: 第62回 北関東医学会
  • Place of Presentation: 前橋
  • Year and Date: 2015-10-01
  • Invited
• [Presentation] ゲニステイン及びダイゼインのステロイド生体異物受容体とシトクロムP450モノオキシゲナーゼ3A4を介する代謝機構 (2015)
  • Author(s): 岩崎俊晴, Winda Ariyani, 早坂香保里, 栗原光累, 飯塚祐基, Ronny Lesmana, 下川哲昭, 鯉淵典之
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21 – 2015-05-24
• [Presentation] Hormone and cerebellar development. (2015)
  • Author(s): Koibuchi N.
  • Organizer: 7th International Symposium of the Society for Research on the Cerebellum.
  • Place of Presentation: Brussels, Belgium
  • Year and Date: 2015-05-08
  • Int'l Joint Research / Invited
• [Presentation] プルキンエ細胞におけるドミナントネガティブ甲状腺ホルモン受容体の小脳発達に対する影響 (2015)
  • Author(s): 岩崎俊晴，于露，下川哲昭，鯉淵典之
  • Organizer: 第120回 日本解剖学会総会･全国学術集・第92回 日本生理学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 有酸素運動によるラット骨格筋における Na+/K+-ATPase 発現の増強 (2015)
  • Author(s): 飯塚祐基，栗原光累，岩崎俊晴，Ronny Lesmana,，下川哲昭，鯉淵典之
  • Organizer: 第120回 日本解剖学会総会･全国学術集・第92回 日本生理学会大会合同大会 2015年3月21-23日(月) 神戸
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] ヒト成長の生理学 「合同教育プログラム」 (2015)
  • Author(s): 鯉淵典之
  • Organizer: 第120回 日本解剖学会総会･全国学術集・第92回 日本生理学会大会合同大会 2015年3月21-23日(月) 神戸
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 天然植物イソフラボンのステロイド生体異物受容体(SXR)とシトクロムP450モノオキシゲナーゼ3A4(CYP3A4)を介する薬物代謝機構 (2014)
  • Author(s): 岩崎俊晴，Winda Ariyani，早坂香保里，栗原光累，飯塚祐基，Ronny Lesmana，下川哲昭，鯉淵典之
  • Organizer: 環境ホルモン学会第17回研究発表会
  • Place of Presentation: 東京
  • Year and Date: 2014-12-09 – 2014-12-10
• [Presentation] Polybrominated biphenyl mixture, BP-6による甲状腺ホルモンを介する脳発達の抑制 (2014)
  • Author(s): 岩崎俊晴，Kingsley Ibhazehiebo，鯉淵典之
  • Organizer: 第57回日本甲状腺学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-11-13 – 2014-11-15
• [Presentation] 有酸素運動によるラット骨格筋における甲状腺ホルモン感受性の変化 (2014)
  • Author(s): 鯉淵典之，Ronny Lesmana, 岩崎俊晴
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 脳発達におけるPerfluolooctane sulfonate (PFOS)とPerfluorooctanoic acid (PFOA)の影響 (2014)
  • Author(s): 岩崎俊晴，蓜島旭，宮坂勇平，Yu Lu，原口瑞樹，高鶴裕介，下川哲昭，鯉淵典之
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 内分泌かく乱化学物質による甲状腺ホルモン系のかく乱（教育講演） (2014)
  • Author(s): 鯉淵典之
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-04-24 – 2014-04-26
• [Book] リッピンコットイラストレイテッド生理学 (2014)
  • Author(s): 岩崎俊晴 他（訳） 鯉淵典之，栗原敏（監訳）
  • Total Pages: 629
  • Publisher: 丸善出版
• [Remarks] 群馬大学医学系研究科 応用生理学分野
  • URL: http://nori3.dept.med.gunma-u.ac.jp/
• [Remarks] 群馬大学医学系研究科応用生理学分野
  • URL: http://nori3.dept.med.gunma-u.ac.jp/