Cl-homeodynamics and resulting GABA_A-receptor-mediated functional changes underlying the cortical developmental disorder induced by stress

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390058
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: FUKUDA Atsuo Hamamatsu University School of Medicine, 医学部・生理学第一講座, 教授 (50254272)
• Co-Investigator(Kenkyū-buntansha): KUMADA Tatsurou 浜松医科大学, 医学部, 助教 (00402339) ; FURUKAWA Tomonori 浜松医科大学, 医学部, 助教 (60402369) ; MORISHIMA Toshitaka 浜松医科大学, 医学部, 助教 (60456548)
• Project Period (FY): 2007 – 2009
• Keywords: 細胞移動 / 母体ストレス / GABA / グルタミン酸 / 大脳皮質 / 皮質形成異常 / 線条体原基 / 神経発生

Research Abstract

妊娠中の精神的ストレスが出生児の脳機能に与える影響が懸念されている。これらストレス脆弱性には臨界期が存在すると考えられる。そこで、神経細胞の種類と細胞発生時期を識別できるモデルマウスを作製し、母体ストレスあるいは出生直後の傷害ストレスが仔脳のGABA作用を撹乱し、細胞の分化・移動の障害を誘発することを明らかにした。さらに細胞種や分化・移動ステージでの感受性の差を解析し、母体ストレスや周産期脳傷害による発達障害の発生メカニズムを検討した。

Research Products

• [Journal Article] Dominant negative mutations inα-II spectrin cause early onset West syndrome with severe cerebral hypomyelination, spastic quadriplegia, and developmental delay. (2010)
  • Author(s): Saitsu, H., Tohyama, J., Kumada, T., Egawa, K., Hamada, K., Okada, I., Mizuguchi, T., Osaka, H., Miyata, R., Furukawa, T., Haginoya, K., Hoshino, H., Goto, T., Hachiya, Y., Yamagata, T., Saitoh, S., Nagai, T., Nishiyama, K., Nishimura, A., Miyake, N., Komada, M., Hayashi, K., Hirai, S., Ogata, Kazuhiro., Kato, M., Fukuda, A., Matsumoto N.
  • Journal Title: Am. J. Human Genet. (in press)
  • Peer Reviewed
• [Journal Article] GABA imaging in brain slices using immobilized enzyme-linked photo analysis. (2010)
  • Author(s): Morishima, T., Uematsu, M., Furukawa, T., Yanagawa, Y., Fukuda, A., Yoshida, S.
  • Journal Title: Neurosci. Res (in press)
  • Peer Reviewed
• [Journal Article] Difference in binocularity and ocular dominance plasticity between GABAergic and excitatory cortical neurons. (2010)
  • Author(s): Kameyama, K., Sohya, K., Ebina, T., Fukuda, A., Yanagawa, Y., Tsumoto, T.
  • Journal Title: J. Neurosci 30 Pages: 1551-1559
  • Peer Reviewed
• [Journal Article] Glycine receptors mediate excitation of subplate neurons in neonatal rat cerebral cortex. (2008)
  • Author(s): Kilb, W., Hanganu, I.L., Okabe, A., Shimizu-Okabe, C., Fukuda, A., Luhmann, H.J.
  • Journal Title: J. Neurophysiol 100 Pages: 698-707
  • Peer Reviewed
• [Journal Article] Induction of amyloid βaccumulation by ER calcium disruption and resultant upregulation of angiogenic factors in ARPE19 cells. (2008)
  • Author(s): Koyama, Y., Matsuzaki, S., Gomi, F., Yamada., K., Katayama, T., Sato, K., Kumada, T., Fukuda, A., Matsuda, S., Tano, Y., Tohyama, M.
  • Journal Title: Invest. Ophthalmol. Visual Sci 49 Pages: 2376-2383
  • Peer Reviewed
• [Journal Article] De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. (2008)
  • Author(s): Saitsu, H., Kato, M., Mizuguchi, T., Hamada, K., Osaka, H., Tohyama, J., Uruno, K., Kumada, S., Nishiyama, K., Nishimura, A., Okada, I., Yoshimura, Y., Hirai, S., Kumada, T., Hayasaka, K., Fukuda, A., Ogata, K., Matsumoto, N.
  • Journal Title: Nat. Genet 40 Pages: 782-788
  • Peer Reviewed
• [Journal Article] Changes in the expression of cation-Clcotransporters, NKCC1 and KCC2, during cortical malformation induced by neonatal freeze-lesion. (2007)
  • Author(s): Shimizu-Okabe, C., Okabe, A., Kilb, W., Sato, K., Luhmann, H.J., Fukuda, A.
  • Journal Title: Neurosci. Res 59 Pages: 288-295
  • Peer Reviewed
• [Journal Article] Kinetic properties of Cl-uptake mediated by Na+-dependent K+-2Cl-cotransport in immature rat neocortical neurons. (2007)
  • Author(s): Achilles, K., Okabe, A., Ikeda, M., Shimizu-Okabe, C., Yamada, J., Fukuda, A., Luhmann, H.J., Kilb, W.
  • Journal Title: J. Neurosci 27 Pages: 8616-8627
  • Peer Reviewed
• [Journal Article] Molecular basis for the GABAA receptor-mediated tonic inhibition in rat somatosensory cortex. (2007)
  • Author(s): Yamada, J., Furukawa, T., Ueno, S., Yamamoto, S., Fukuda, A.
  • Journal Title: Cereb. Cortex 17 Pages: 1782-1787
  • Peer Reviewed
• [Journal Article] Insertion ofα7 nicotinic receptors at neocortical layer V GABAergic synapses is induced by a benzodiazepine, midazolam. (2007)
  • Author(s): Yamamoto, S., Yamada, J., Ueno, S., Kubota, H., Furukawa, T., Yamamoto, S., Fukuda, A.
  • Journal Title: Cereb. Cortex 17 Pages: 653-660
  • Peer Reviewed
• [Presentation] Chloride homeo-dynamics causing GABA modal shift during development and pathogenesis. (2010)
  • Author(s): Fukuda, A.
  • Organizer: FENS/ Hertie WINTER SCHOOL 2010 Obergurgl
  • Place of Presentation: Austria
  • Year and Date: 20100110-20100117
• [Presentation] 幼少時の麻酔暴露による脳障害と脳発達過程の興奮性GABA作用. (2009)
  • Author(s): 福田敦夫
  • Organizer: 第29回日本臨床麻酔学会大会
  • Place of Presentation: 浜松
  • Year and Date: 20091029-20091031
• [Presentation] Endogenous taurine tonically activates GABAA receptors in embryonic mouse neocortex. (2009)
  • Author(s): Fukuda, A., Furukawa, T., Morishima, T., Kumada, T.
  • Organizer: The 40th NIPS International Symposium: International Joint Symposium 2009 "Physiology of Anion Transport" and "Cell Volume Regulation"(PAT-CVR, 2009)
  • Place of Presentation: Okazaki
  • Year and Date: 20090803-20090806
• [Presentation] Physiological significance of taurine-mediated Cl- conductances during corticogenesis. In Symposium, "Modulation of brain development by paracrine activation of Clconductances. " (2009)
  • Author(s): Fukuda, A.
  • Organizer: The 36th International Congress of Physiological Sciences (IUPS 2009)
  • Place of Presentation: Kyoto
  • Year and Date: 20090721-20090801
• [Presentation] Cl- mediated GABA release from Bergmann glia in developing cerebellar cortex. In Symposium, "Modulation of brain development by paracrine activation of Cl- conductances. " (2009)
  • Author(s): Yoshida, S., Morishima, T., Okochi, K., Takayama, C., Yanagawa, Y., Fukuda, A.
  • Organizer: The 36th International Congress of Physiological Sciences (IUPS 2009)
  • Place of Presentation: Kyoto
  • Year and Date: 20090721-20090801
• [Presentation] Ionotropic GABA receptors control neuronal migration in neonatal rat cerebral cortex. (2009)
  • Author(s): Luhmann, H.J., Kilb, W., Fukuda, A.
  • Organizer: The 36th International Congress of Physiological Sciences (IUPS 2009)
  • Place of Presentation: Kyoto
  • Year and Date: 20090721-20090801
• [Presentation] Physiological roles of taurine-mediated tonic GABAA-receptor activation in corticogenesis. (2009)
  • Author(s): Fukuda, A.
  • Organizer: The 2nd International Symposium Topical Problems of Biophotonics-2009
  • Place of Presentation: Nizhny Novgorod
  • Year and Date: 20090719-20090724
• [Presentation] Ambient GABA and taurine during corticogenesis. (2009)
  • Author(s): Fukuda, A., Furukawa, T., Morishima, T., Kumada, T.
  • Organizer: 2009 IUPS, International Conference of Physiological Science and 8th Korea-Japan Joint Symposium, Busan
  • Place of Presentation: Korea
  • Year and Date: 20090115-20090117
• [Presentation] Changes in KCC2 and NKCC1 expressions in spinal nucleus and ganglion of the trigeminal nerve in a rat model of trigeminal neuropathic pain. (2008)
  • Author(s): Fukuda, A., Wei, B., Furukawa, T., Kumada, T., Sato, K.
  • Organizer: The 6th Forum of European Neuroscience
  • Place of Presentation: Geneva, Switzerland
  • Year and Date: 20080712-20080716
• [Presentation] The Cl- homeo-dynamics modulates GABA actions and hence the neural network dynamics. (2008)
  • Author(s): Fukuda, A.
  • Organizer: ISTC-RIKEN BSI workshop (44th Japan Workshop): Bridging non-linear dynamics with cellular and molecular neuroscience
  • Place of Presentation: Wako
  • Year and Date: 20080318-20080319
• [Presentation] Rat facial hyperalgesia induced by the trigeminal nerve constriction is associated with changes in Cltransporters expression in the spinal nucleus and the ganglion. (2007)
  • Author(s): Fukuda, A., Wei, B., Furukawa, T., Kumada, T., Okabe, A., Ohno, K., Sato, K.
  • Organizer: The 7th Japan-Korea Joint Symposium of Brain Sciences, and Cardiac and Smooth Muscles
  • Place of Presentation: Sendai
  • Year and Date: 20071207-20071209
• [Presentation] 塩素イオンはどのように脳の機能を変えるか? (2007)
  • Author(s): 福田敦夫
  • Organizer: 第12回静岡健康・長寿学術フォーラム
  • Place of Presentation: 静岡
  • Year and Date: 20071019-20071020
• [Presentation] Modal shift of the tonic GABAA receptor-mediated conductance during neocortical development, "Mechanisms and functional significance of tonic GABAA receptor mediated conductance. (2007)
  • Author(s): Atsuo Fukuda
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 20070910-20070912
• [Presentation] 脳神経細胞の応答の多様性を調べる研究方法と課題. (2007)
  • Author(s): 福田敦夫
  • Organizer: メディカルイノベーションフォーラム2007 HAMAMATSU
  • Place of Presentation: 浜松
  • Year and Date: 2007-11-20
• [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18回メディカルホトニクスコース講習テキスト) (2009)
  • Author(s): 福田敦夫
  • Total Pages: 95-114
• [Book] 動物モデルからヒトへ(ベビーサイエンス) (2008)
  • Author(s): 福田敦夫
  • Total Pages: 33-35
• [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17回メディカルホトニクスコース講習テキスト) (2008)
  • Author(s): 福田敦夫
  • Total Pages: 101-120
• [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16回メディカルホトニクスコース講習テキスト) (2007)
  • Author(s): 福田敦夫
  • Total Pages: 113-132
• [Remarks]
  • URL: http://www2.hama-med.ac.jp/w1a/phys1/index-j.html