The formation of GABAergic network and rhyhm of repiratory in the embryonic development

• Project/Area Number: 25430066
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: University of the Ryukyus
• Principal Investigator: SHIMIZU Chigusa 琉球大学, 医学(系)研究科(研究院), 特命助教 (70435072)
• Co-Investigator(Kenkyū-buntansha): OKABE Akihito 琉球大学, 大学院医学研究科, 准教授 (10313941)
• Co-Investigator(Renkei-kenkyūsha): TAKAYAMA Chitoshi 琉球大学, 大学院医学研究科, 教授 (60197217) ; YANAGAWA Yuchio 群馬大学, 大学院医学研究科, 教授 (90202366)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: GABA / KCC2 / hypogrossal / VGAT / GAD / 呼吸リズム / 舌下神経核 / 細胞内Cl-濃度 / 延髄

Outline of Final Research Achievements

GABA plays important roles in the respiratory rhythm. Role of GABAergic transmission in regulation of medullary respiration-related rhythmic activity (RRA) perinatally, however is yet to be determined. In this study the numbers of RRA were significantly increased in embryonic development but there were no significant changes after birth. VGAT transports GABA to synaptic vesicles. GABAergic action is changed from excitatory to inhibitory by expression of KCC2. Both VGAT and KCC2 deficient mice die in their birthday by respiratory failure. By compared these mice, it found that exocytosis of GABA is necessary to generate RRA, however KCC2 needs for making of rhythm of respiratory. .

Research Products

• [Journal Article] A novel insulinotropic mechanism of whole grain-derived γ-oryzanol via the suppression of local dopamine D2 receptor signalling in mouse islet. (2015)
  • Author(s): Kozuka C, Sunagawa S, Ueda R, Higa M, Ohshiro Y, Tanaka H, Shimizu-Okabe C, Takayama C, Matsushita M, Tsutsui M, Ishiuchi S, Nakata M, Yada T, Miyazaki JI, Oyadomari S, Shimabukuro M, Masuzaki H.
  • Journal Title: Br J Pharmacol Volume: 172 Issue: 18 Pages: 4519-4534
  • DOI: 10.1111/bph.13236
  • Peer Reviewed
• [Journal Article] γ-oryzanol protects pancreatic β-cells against endoplasmic reticulum stress in male mice. (2015)
  • Author(s): Kozuka C, Sunagawa S, Ueda R, Higa M, Tanaka H, Shimizu-Okabe C, Ishiuchi S, Takayama C, Matsushita M, Tsutsui M, Miyazaki JI, Oyadomari S, Shimabukuro M, Masuzaki H
  • Journal Title: Endocrinology Volume: 156 Issue: 4 Pages: 1242-1250
  • DOI: 10.1210/en.2014-1748
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] KCC2-mediated regulation of respiration-related rhythmic activity during postnatal development in mouse medulla oblongata. (2015)
  • Author(s): Okabe A., Shimizu-Okabe C., Arata A., Konishi S., Fukuda A., and Takayama C.
  • Journal Title: Brain Res. Volume: 1601 Pages: 31-39
  • DOI: 10.1016/j.brainres.2015.01.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of a novel cell-penetrating peptide targeting human glioblastoma cell lines as a cancer-homing transporter. (2015)
  • Author(s): Higa M, Katagiri C, Shimizu-Okabe C, Tsumuraya T, Sunagawa M, Nakamura M, Ishiuchi S, Takayama C, Kondo E, Matsushita M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 457(2) Issue: 2 Pages: 206-12
  • DOI: 10.1016/j.bbrc.2014.12.089
  • Peer Reviewed / Open Access
• [Journal Article] Role of neuropsin in parvalbumin immunoreactivity changes in hippocampal basket terminals of mice reared in various environments (2014)
  • Author(s): Suzuki H, Kanagawa D, Nakazawa H, Tawara-Hirata Y, Kogure Y, Shimizu-Okabe C, Takayama C, Ishikawa Y, Shiosaka S
  • Journal Title: Front Cell Neurosci Volume: ８ Pages: 420-420
  • DOI: 10.3389/fncel.2014.00420
  • Peer Reviewed / Open Access
• [Journal Article] Embryonic development of GABAergic signaling in the mouse spinal trigeminal nucleus interpolaris (2014)
  • Author(s): Hidemichi Kin, Jeongtae Kim, Chigusa Shimizu-Okabe, Akihito Okabe, Chitoshi Takayama
  • Journal Title: Neuroscience Letters Volume: 566 Pages: 221-225
  • DOI: 10.1016/j.neulet.2014.02.057
  • Peer Reviewed
• [Journal Article] Characteristic development of the GABA-removal system in the mouse spinal cord. (2014)
  • Author(s): Kim J, Kosaka Y, Shimizu-Okabe C, Niizaki A, Takayama C.
  • Journal Title: Neuroscience. Volume: 262 Pages: 129-142
  • Peer Reviewed
• [Journal Article] 子持ち研究者, 日本解剖学会男女共同参画ワークショップに参加する (2013)
  • Author(s): 清水千草
  • Journal Title: 解剖学雑誌 Volume: 88 Pages: 67-68
  • Peer Reviewed
• [Presentation] マウス坐骨神経損傷モデルにおけるGABA伝達関連分子の発現変化 (2016)
  • Author(s): 小坂祥範、屋富祖司、金正泰、清水千草、高山千利
  • Organizer: 第121回日本解剖学会
  • Place of Presentation: ビッグパレットふくしま（福島県福島市）
  • Year and Date: 2016-03-28
• [Presentation] wx/ae brown rice reduced the fat accumulation and improved dyslipidemia. (2016)
  • Author(s): Chigusa Shimizu,Chisayo Kozuka, Shiori Kobayashi, Yu Miyazaki, Jeongtae Kim, Hiroaki Masuzaki, Chitoshi Takayama.
  • Organizer: 第93回日本生理学会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-22
• [Presentation] マウス坐骨神経損傷モデルにおけるGABA伝達関連分子の発現変化 (2016)
  • Author(s): 小坂祥範、屋富祖司、金正泰、清水千草、高山千利
  • Organizer: 第93回日本生理学会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-22
• [Presentation] Development of inhibitory system in the mouse spinal cord (2016)
  • Author(s): 清水千草
  • Organizer: 第93回日本生理学会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-22
• [Presentation] Sequential embryonic development of GABAergic input the hypothalamus (2015)
  • Author(s): Shimizu-Okabe C., Kobayashi M., Kim J., Niizaki A., Matsushita M., Masuzaki H., and Takayama C.
  • Organizer: 第38回日本神経科学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28 – 2015-07-31
• [Presentation] Development of glycinergic system in the mouse spinal cord. (2015)
  • Author(s): Sunagawa M., Shimizu-Okabe C., Kim J., Kobayashi S., and Takayama C.
  • Organizer: 第38回日本神経科学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28 – 2015-07-31
• [Presentation] Sequential embryonic development of GABAergic input the hypothalamus (2015)
  • Author(s): Shimizu-Okabe C., Kobayashi M., Kim J., Niizaki A., Matsushita M., Masuzaki H., and Takayama C.
  • Organizer: 第38回日本神経科学会
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2015-07-28
• [Presentation] Development of glycinergic system in the mouse spinal cord. (2015)
  • Author(s): Sunagawa M., Shimizu-Okabe C., Kim J., Kobayashi S., and Takayama C.
  • Organizer: 第38回日本神経科学会
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2015-07-28
• [Presentation] 玄米由来生理活性物質が担う新規の膵島機能・インスリン分泌調節機構の解明 (2015)
  • Author(s): 小塚智沙代、比嘉盛丈、田仲秀明、砂川澄人、植田玲、清水千草、高山千利、松下正之、親泊政一、島袋充生、益崎裕章
  • Organizer: 第58回 日本糖尿病学会年次学術集会
  • Place of Presentation: 山口
  • Year and Date: 2015-05-21 – 2015-05-24
• [Presentation] 玄米由来生理活性物質が担う新規の膵島機能・インスリン分泌調節機構の解明 (2015)
  • Author(s): 小塚智沙代、比嘉盛丈、田仲秀明、砂川澄人、植田玲、清水千草、高山千利、松下正之、親泊政一、島袋充生、益崎裕章
  • Organizer: 第58回 日本糖尿病学会年次学術集会
  • Place of Presentation: 海峡メッセ下関（山口県下関市）
  • Year and Date: 2015-05-21
• [Presentation] 玄米有効成分による膵内分泌機能改善の新たな分子機構 (2015)
  • Author(s): 小塚智沙代、砂川澄人、比嘉盛丈、池間朋己、田仲秀明、清水千草、高山千利、松下正之、親泊政一、島袋充生、益崎裕章
  • Organizer: 第52回 日本臨床分子医学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2015-04-10 – 2015-04-11
• [Presentation] 玄米有効成分による膵内分泌機能改善の新たな分子機構 (2015)
  • Author(s): 小塚智沙代、砂川澄人、比嘉盛丈、池間朋己、田仲秀明、清水千草、高山千利、松下正之、親泊政一、島袋充生、益崎裕章
  • Organizer: 第52回 日本臨床分子医学会学術集会
  • Place of Presentation: みやこメッセ（京都府京都市）
  • Year and Date: 2015-04-10
• [Presentation] Kinase activity of TRPM7 regulates lipid metabolism. (2015)
  • Author(s): Katagiri C., Taku K., Shimizu C., Kozuka C., Konishi M., Tomizawa K., Takayama C., Mazuzaki H., Kozak A., and Matsushita M.
  • Organizer: 第120回日本解剖学会・第92回日本生理学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Identification of novel target genes of mood stabilizer treatment. (2015)
  • Author(s): Takamatsu G., Shimizu C., Katagiri C., Tsumuraya T., Hayakawa T., Kondo T., and Takayama C., Matsushita M.
  • Organizer: 第120回日本解剖学会・第92回日本生理学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] GABAergic signaling in the developing CNS-GABAergic neurons and GABAA receptors. (2015)
  • Author(s): Takayama C., and Shimizu C.
  • Organizer: 第120回日本解剖学会・第92回日本生理学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Perinatal modulations of the respiration-related rhythmic activities by GABA and Cl- co-transporters (2015)
  • Author(s): Okabe A., Shimizu C., and Takayama C.
  • Organizer: 第120回日本解剖学会・第92回日本生理学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 難消化米(wx/ae)による脂肪肝及び脂質異常症の予防・改善効果 (2015)
  • Author(s): Shimizu C., Kozuka C., Kobayashi C., Miyazaki Y., Kim J., Kotaniguchi M., Nakaya M., Kitamura S., Masuzaki H., and Takayama C.
  • Organizer: 第120回日本解剖学会・第92回日本生理学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 双極性障害治療の新規標的分子の同定 (2015)
  • Author(s): 高松岳矢、清水千草、片桐千秋、圓谷智之、早川朋子、近藤 毅、高山千利、松下正之
  • Organizer: 第36回沖縄精神神経学会
  • Place of Presentation: 沖縄
  • Year and Date: 2015-02-07
• [Presentation] マウス脊髄におけるグリシン作動性神経回路の発達変化 (2014)
  • Author(s): 砂川昌信、金正泰、小林しおり、清水千草、高山千利
  • Organizer: 日本解剖学会第70回九州支部学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2014-10-25
• [Presentation] 高脂肪食摂取マウスにおける脂肪肝及び脂質異常症の難消化米(wx/ae)による改善効果 (2014)
  • Author(s): 清水千草、小塚智沙代、小林しおり、宮崎悠、金正泰、益崎裕章、高山千利
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: 宮崎
  • Year and Date: 2014-10-24 – 2014-10-25
• [Presentation] Characteristic development of GABA-removal system in the mouse spinal cord (2014)
  • Author(s): Kim J., Kosaka Y., Shimizu-Okabe C., Niizaki A., and Takayama C.
  • Organizer: 韓国獣医解剖学会
  • Place of Presentation: 韓国
  • Year and Date: 2014-10-17
• [Presentation] Unique development of the GABA-removal system in the mouse spinal cord. (2014)
  • Author(s): Kim J., Kosaka Y., Shimizu-Okabe C., Nizaki A., and Takayama C.
  • Organizer: 第63回韓国解剖学会学術集会
  • Place of Presentation: 韓国
  • Year and Date: 2014-10-16 – 2014-10-18
• [Presentation] 周産期における呼吸リズム形成に対するGABA応答性の変化 (2014)
  • Author(s): 清水千草、岡部明仁、高山千利
  • Organizer: 第57回日本神経化学会
  • Place of Presentation: 奈良
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] ErbB4/パルブアルブミン陽性インターニューロンを介したニューロプシンもよる海馬興奮性神経細胞の制御 (2014)
  • Author(s): 鈴木春満、金河大、中澤瞳、清水千草、高山千利、塩坂貞夫
  • Organizer: 第57回日本神経化学会
  • Place of Presentation: 奈良
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] Unique development of the GABA-removal system in the mouse spinal cord. (2013)
  • Author(s): Kim J, Kosaka Y, Shimizu-Okabe C, Niizaki A, Takayama C.
  • Organizer: 第63回韓国解剖学会学術集会
  • Place of Presentation: 韓国
• [Presentation] GABAergic System in the hypothalamus. (2013)
  • Author(s): Shimizu-Okabe C,Kobayashi M, Niizaki A, Takayama C.
  • Organizer: 第36回内藤コンファレンス
  • Place of Presentation: 札幌
• [Presentation] Distinct development of GABA removing system in the ventral and dorsal horns in the mouse spinal cord. (2013)
  • Author(s): Takayama C, Kim J.,Kosaka Y, Shimizu-Okabe C, Niizaki A.
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 京都
• [Presentation] Developmental changes in the respiration-related rhythmic activity in mouse hypoglossal nucleus. (2013)
  • Author(s): Okabe A, Arata A, Shimizu-Okabe C, Konishi S, Fukuda A, Takayama C.
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 京都
• [Remarks] http://www.u-ryukyu.ac.jp/
• [Remarks] http://w3.u-ryukyu.ac.jp/anatomy2/index.html
• [Remarks] http://w3.u-ryukyu.ac.jp/anatomy2/index.html