Perturbation of developmental Cl^-homeodynamics may underlie fetal and neonatal brain disorders

• Project/Area Number: 23659535
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: FUKUDA Atsuo 浜松医科大学, 医学部, 教授 (50254272)
• Co-Investigator(Renkei-kenkyūsha): INOUE Koichi 浜松医科大学, 医学部, 准教授 (80345818) ; EGAWA Kiyoshi 浜松医科大学, 医学部, 特任研究員 (40450829) ; HATA Kenichiro 国立成育医療研究センター, 部長 (60360335)
• Project Period (FY): 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2011: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: クロライドホメオスタシス / 皮質板細胞 / 大脳皮質 / 細胞移動 / GABA / タウリン / 母体ストレス / 発達障害

Research Abstract

The most major inhibitory neurotransmitter, GABA, induces synaptic inhibition in the adult brain. In immature neurons, however,[ Cl^-]_i is high due to balance of Cl^-transporters, promoting depolarizing GABA action by efflux of Cl^-along with its electrical gradient. Thus GABA evokes excitation and/or non-synaptic tonic depolarization in immature brain. Such multimodal GABA actions during development are necessary for neurogenesis, differentiation, migration, and synaptogenesis. Therfore, perturbation of the developmental Cl^-homeodynamics may underlie fetal and neonatal brain disorders. By using various pathological model mice, we have studied how Cl^-homeodynamics work in pathogenesis of fetal and neonatal disorders of cortical development.

Research Products

• [Journal Article] Phosphodiesterase 4 inhibition enhances the dopamine D1receptor/PKA/DARPP-32 signaling cascade in frontal cortex (2012)
  • Author(s): Kuroiwa, M., Snyder, G. L., Shuto, T., Fukuda, A., Yanagawa, Y., Benavides, D. R., Nairn, A. C., Bibb, J. A., Greengard, P. and Nishi, A.
  • Journal Title: Psychopharmacology Volume: 219 Pages: 1065-1079
  • Peer Reviewed
• [Journal Article] GABA regulates the multidirectional tangential migration of GABAergic interneurons in living neonatal mice (2011)
  • Author(s): Inada, H., Watanabe, M., Uchida, T., Ishibashi, H., Wake, H., Nemoto, T., Yanagawa, Y., Fukuda, A. and Nabekura, J.
  • Journal Title: PLoS ONE Volume: 6 Pages: 277048-277048
  • Peer Reviewed
• [Journal Article] GABA regulates the multidirectional tangential migration of GABAergic interneurons in living neonatal mice (2011)
  • Author(s): Inada, H., et al
  • Journal Title: PLoS ONE Volume: 6
  • Peer Reviewed
• [Journal Article] 神経回路機能の発達と病態(GABAを中心に) (2011)
  • Author(s): 福田敦夫
  • Journal Title: 小児神経学の進歩 Volume: 40 Pages: 129-142
• [Journal Article] 組織標本(脳スライス)への各種イメージング法適用の実際 (2011)
  • Author(s): 福田敦夫
  • Journal Title: メディカルホトニクスコース講習テキスト Volume: 20 Pages: 57-64
• [Journal Article] Does elevated intracellular chloride cause epilepsy in focal cortical dysplasia? (2011)
  • Author(s): Shimizu-Okabe, C., et al
  • Journal Title: Dysplasia : Causes, Types and Treatment Options. eds.Nova Science Publishers, Hauppauge, NY, U.S.A. Volume: (In Press)
• [Journal Article] Chloride homeodynamics underlying pathogenic modal shifts of GABA actions (2011)
  • Author(s): Fukuda, A.
  • Journal Title: Comprehensive Developmental Neuroscience. eds.Pasko Rakic and John Rubenstein. Elsevier, Oxford, United Kingdom Volume: 10章(In Press)
• [Journal Article] Multimodal GABA_A receptor functions on cell development (2011)
  • Author(s): Fukuda, A., et al
  • Journal Title: Comprehensive Developmental Neuroscience. eds.Pasko Rakic and John Rubenstein. Elsevier, Oxford, United Kingdom Volume: 125章(In Press)
• [Journal Article] Guidepost Neurons for the Lateral Olfactory Tract : Expression of Metabotropic Glutamate Receptor 1 and Innervation by Glutamatergic Olfactory Bulb Axons
  • Author(s): Hirata, T., Kumada, T., Kawasaki, T., Furukawa, T., Aiba, A. Conquet, F., Saga, Y. and Fukuda, A.
  • Journal Title: Dev. Neurobiol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Taurine inhibits the K^+-Cl^-cotransporter KCC2 to regulate embryonic Cl^-homeostasis via the with-no-lysine(WNK) protein kinase signaling pathway
  • Author(s): Inoue, K., Furukawa, T., Kumada, T., Yamada, J., Wang, T., Inoue, R. and Fukuda, A.
  • Journal Title: J. Biol. Chem. Volume: (in press)
  • Peer Reviewed
• [Presentation] 三叉神経痛の動物モデルと病態仮説 (2012)
  • Author(s): 福田敦夫
  • Organizer: 第14回日本脳神経減圧術学会
  • Place of Presentation: 東京
  • Year and Date: 2012-01-19
• [Presentation] 三叉神経痛の動物モデルと病態仮説 (2012)
  • Author(s): 福田敦夫
  • Organizer: 第14回日本脳神経減圧術学会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2012-01-19
• [Presentation] Regionally differential calcium oscillation of radially migrating cells in embryonic cortex (2012)
  • Author(s): Nakanishi, Y., Kumada, T., Furukawa, T., Egawa, K. and Fukuda, A.
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 長野
• [Presentation] Ambient taurine controls radial migration in developing cerebral cortex.細胞外タウリンは発達期大脳皮質のradial migrationを制御する (2012)
  • Author(s): Furukawa, T., Yamada, J., Inoue, K., Yanagawa, Y., Matsushima, Y. and Fukuda, A.
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 長野
• [Presentation] Intracellular taurine modulates KCC2 function by phosphorylation.細胞内タウリンによるKCC2蛋白活性のリン酸化を介した修飾 (2012)
  • Author(s): Fukuda, A., Inoue, K., Furukawa, T., Yamada, J., Kumada, T., Wang, T. and Inoue, R.
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 長野
• [Presentation] 大脳皮質形成における非シナプス性GABA (2012)
  • Author(s): 福田敦夫
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨
• [Presentation] Abnormal Chloride Transportation in Cortical Dysplasia. (2012)
  • Author(s): Fukuda, A.
  • Organizer: International Symposium on Surgery for Catastrophic Epilepsy in Infants(ISCE)
  • Place of Presentation: Tokyo Japan
• [Presentation] Abnormal Chloride Transportation in Cortical Dysplasia (2012)
  • Author(s): Fukuda, A.
  • Organizer: International Symposium on Surgery for Catastr ophicEpilepsy in Infants (ISCE)
  • Place of Presentation: Tokyo, Japan(招待講演)
• [Presentation] 大脳皮質形成における非シナプス性GABA (2012)
  • Author(s): 福田敦夫
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨(招待講演)
• [Presentation] Intracellular taurine modulates KCC2 function by phosphorylation (2012)
  • Author(s): Fukuda, A., et al
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 長野
• [Presentation] アンジェルマン症候群における小脳顆粒細胞tonic inhibitionの低下と小脳機能障害 (2011)
  • Author(s): 江川潔,井上浩一,斉藤伸治,木住野達也,福田敦夫
  • Organizer: 平成23年度生理学研究会シナプス2011
  • Place of Presentation: 岡崎
• [Presentation] Taurine prevents KCC2 from functioning in a phosphorylation-dependent manner to render embryonic Cl^-homeostasis (2011)
  • Author(s): Inoue, K., Furukawa, T., Yamada, J., Kumada, T., Wang, T., Inoue, R. and Fukuda, A.
  • Organizer: 41st Annual Meeting, Society for Neuroscience
  • Place of Presentation: Washington, D. C., U. S. A.
• [Presentation] Impairment of tonic inhibition in cerebellum granule cells causes cerebellum dysfunction in Ube3a maternal-deficient mice (2011)
  • Author(s): Egawa, K., Inoue, K., Saitoh, S., Kishino, T. and Fukuda, A.
  • Organizer: 41st Annual Meeting, Society for Neuroscience
  • Place of Presentation: Washington, D. C., U. S. A.
• [Presentation] Ambient GABA released from Bergmann glial cells promotes proliferation of cerebellar granule cell precursors. (2011)
  • Author(s): Fukuda, A., Morishima, T., Kumada, T., Takayama, C. and Yoshida, S.
  • Organizer: 41st Annual Meeting, Society for Neuroscience
  • Place of Presentation: Washington, D. C., U. S. A.
• [Presentation] 生後初期に一過性のバーグマングリア由来の細胞外GABAが小脳顆粒前駆細胞の分裂を促進する (2011)
  • Author(s): 森島寿貴,熊田竜郎,高山千利,吉田祥子,福田敦夫
  • Organizer: 第58回中部生理学会
  • Place of Presentation: 福井
• [Presentation] 発達期の大脳皮質の各領域における移動細胞のカルシウム振動 (2011)
  • Author(s): 中西康彦,福田敦夫,熊田竜郎,古川智範,江川潔
  • Organizer: 第58回中部生理学会
  • Place of Presentation: 福井
• [Presentation] アンジェルマン症候群における小脳顆粒細胞tonic inhibitionの低下と小脳機能障害 (2011)
  • Author(s): 江川潔,井上浩一,斉藤伸治,木住野達也,福田敦夫
  • Organizer: 第38回日本脳科学会
  • Place of Presentation: 沖縄
• [Presentation] Temporal paracrine GABA and KCC2 downregulation underlie the formation of microgyrus in a model of focal cortical malformation (2011)
  • Author(s): Fukuda, A., Wang, T., Kumada, T., Morishima, T. and Yanagawa, Y.
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] GABAergic dysfunction in Ube3a deficient mice, models of angelman syndrome (2011)
  • Author(s): Egawa, K., Inoue, K., Saitoh, S., Kishino, T. and Fukuda, A.
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Developmental regulation of KCC2 activity by taurine in a phosphorylation-dependent manner (2011)
  • Author(s): Inoue, K., Furukawa, T., Yamada, J., Kumada, T., Wang, T., Inoue, R. and Fukuda, A.
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Impairment of tonic inhibition in cerebellum granule cells causes cerebellum dysfunction in Ube3a maternal-deficient mice (2011)
  • Author(s): Egawa, K., Inoue, K., Saitoh, S., Kishino, T. and Fukuda, A.
  • Organizer: Angelman Syndrome Foundation Scientific Symposium
  • Place of Presentation: Salt Lake City, U. S. A.
• [Presentation] Bidirectional interaction of Maternal stress with fetal and maternalγ-amino butyric acid(GABA) systems (2011)
  • Author(s): Uchida, T., Oki, Y., Yanagawa, Y. and Fukuda, A.
  • Organizer: International Symposium "Interaction of nervous and immune systems in health and disease"
  • Place of Presentation: Saint Petersburg, Russia
• [Presentation] Bidirectional interaction of Maternal stress with fetal and maternal γ-aminobutyric acid (GABA) systems (2011)
  • Author(s): Fukuda, A., et al
  • Organizer: International Symposium "Interaction of nervous and immune systems in health and disease"
  • Place of Presentation: Saint Petersburg, Russia(招待講演)
• [Presentation] Impairment of tonic inhibition in cerebellum granule cells causes cerebellum dysfunction in Ube3a maternal-deficient mice (2011)
  • Author(s): Egawa, K., et al
  • Organizer: Angelman Syndrome Foundation Scientific Symposium
  • Place of Presentation: Sheraton Salt Lake City, USA
• [Presentation] Temporal paracrine GABA and KCC2 downregnlation underlie the formation of microgyrus in a model of focal cortical malformation (2011)
  • Author(s): Fukuda, A., et al
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Ambient GABA released from Bergmann glial cells promotes proliferation of cerebellar granule cell precursors (2011)
  • Author(s): Fukuda, A., et al
  • Organizer: 41st Annual Meeting, Society for Neuroscience
  • Place of Presentation: Washington, D.C., USA
• [Presentation] Impairment of tonic inhibition in cerebellum granule cells causes cerebellumdysfunction in Ube3a maternal-deficient mice (2011)
  • Author(s): Egawa, K., et al
  • Organizer: 41st Annual Meeting, Society for Neuroscience
  • Place of Presentation: Washington, D.C., USA
• [Presentation] Taurine prevents KCC2 from functioning in a phosphorylation-dependent manner to render embryonic C1-homeostasis (2011)
  • Author(s): Inoue, K., et al
  • Organizer: 41st Annual Meeting, Society for Neuroscience
  • Place of Presentation: Washington, D.C., USA
• [Presentation] Ambient taurine controls radial migration in developing cerebral cortex (2011)
  • Author(s): Furukawa, T., et al
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 長野
• [Book] 神経回路機能の発達と病態 (2011)
  • Author(s): 福田敦夫
  • Publisher: 小児神経学の進歩
• [Book] 組織標本(脳スライス)への各種イメージング法適用の実際,第20回メディカルホトニクスコース講習テキスト (2011)
  • Author(s): 福田敦夫
• [Book] Does elevated intracellular chloride cause epilepsy in focal cortical dysplasia?
  • Author(s): Shimizu-Okabe, C., Okabe, A. and Fukuda, A.
  • Publisher: Nova Science Publishers
• [Book] Multimodal GABAA receptor functions on cell development
  • Author(s): Fukuda, A., Nakanishi, Y., Kumada, T. and Furukawa, T.
  • Publisher: Elsevier
• [Book] Chloride homeodynamics underlying pathogenic modal shifts of GABA actions. Chapter 10.
  • Author(s): Fukuda, A
  • Publisher: Elsevier
• [Remarks]
  • URL: http://www2.hama-med.ac.jp/w1a/phys1/index-j.html
• [Remarks]
  • URL: http://www2.hama-med.ac.jp/w1a/phys1/index-j.html