Roles of mTOR in neuronal development, synaptic plasticity and learning and memory

• Project/Area Number: 22300106
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: The University of Tokyo
• Principal Investigator: AIBA Atsu 東京大学, 大学院・医学系研究科, 教授 (20271116)
• Co-Investigator(Kenkyū-buntansha): KASSAI Hidetoshi 東京大学, 大学院・医学系研究科, 助教 (40403232) ; HARADA Takeshi 東京大学, 大学院・医学系研究科, 助教 (30362768)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2011: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2010: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 脳・神経 / 遺伝学 / シグナル伝達 / 神経科学

Research Abstract

Aberrant activation of mTOR pathway has been found in many human neurological diseases such as tuberous sclerosis and autism. To determine mTOR function in neurons, transgenic mice having constitutively active mTOR mutant were generated and analyzed. Forebrain-specific active mTOR transgenic mice displayed epileptic seizure and neurodegeneration. Abnormalities of both neuronal morphology and synapse elimination were induced by the activation of mTOR pathway in cerebellar Purkinje cells. These results will provide insights into pathogenic mechanisms of human diseases.

Research Products

• [Journal Article] Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion viamodulation of F-actin. (2013)
  • Author(s): Asahara S, Shibutani Y, Teruyama K, Inoue HY, Kawada Y, Etoh H, Matsuda T, Kimura-Koyanagi M, Hashimoto N, Sakahara M, Fujimoto W, Takahashi H, Ueda S, Hosooka T, Satoh T, Inoue H, Matsumoto M, Aiba A, Kasuga M, Kido Y
  • Journal Title: Diabetologia
  • Peer Reviewed
• [Journal Article] Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin (2013)
  • Author(s): Asahara S
  • Journal Title: Diabetologia Volume: なし Issue: 5 Pages: 1088-1097
  • DOI: 10.1007/s00125-013-2849-5
  • Peer Reviewed
• [Journal Article] Guidepost neurons for the lateral olfactory tract : expression of metabotropic glutamate receptor 1 and linnervation by glutamatergic olfactory bulb axons (2012)
  • 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) Issue: 12 Pages: 1559-1576
  • DOI: 10.1002/dneu.22030
  • Peer Reviewed
• [Journal Article] Functional coupling of the metabotropic glutamate receptor, InsP3 receptor and L-type Ca2+ channel in mouseCA1 pyramidal cells. (2012)
  • Author(s): Kato HK, Kassai H, Watabe AM, Aiba A, Manabe T
  • Journal Title: Journal of Physiology Volume: 590 Issue: 13 Pages: 3019-3034
  • DOI: 10.1113/jphysiol.2012.232942
  • Peer Reviewed
• [Journal Article] In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling. (2012)
  • Author(s): Nishimura S, Manabe I, Nagasaki M, Kakuta S, Iwakura Y, Takayama N, Ooehara J, Otsu M, Kamiya A, Petrich BG, Urano T, Kadono T,Sato S, Aiba A, Yamashita H, Sugiura S, Kadowaki T, Nakauchi H, Eto K, Nagai R
  • Journal Title: Blood Volume: 119
  • Peer Reviewed
• [Journal Article] Cdc42 is required for chondrogenesis and interdigital programmed cell death during limb development (2011)
  • Author(s): Aizawa R, Yamada A, Suzuki D, Iimura T, Kassai H, Harada T, Tsukasaki M, Yamamoto G, Tachikawa T, Nakao K, Yamamoto M, Yamagchi A, Aiba A, Kamijo R
  • Journal Title: AMech Dev Volume: (In press) Issue: 1-4 Pages: 38-50
  • DOI: 10.1016/j.mod.2012.02.002
  • Peer Reviewed
• [Journal Article] Suppression of a neocortical potassium channel activity by intracellular amyloid-β and its rescue with Homer1a. (2011)
  • Author(s): Yamamoto K, Ueta Y, Wang L, Yamamoto R, Inoue N, Inokuchi K, Aiba A, Yonekura H, Kato N.
  • Journal Title: Journal of Neuroscience Volume: 31 Issue: 31 Pages: 11100-11109
  • DOI: 10.1523/jneurosci.6752-10.2011
  • Peer Reviewed
• [Journal Article] Glutamate Receptor delta 2 Is Essential for Input Pathway-Dependent Regulation of Synaptic AMPAR Contents in Cerebellar Purkinje Cells (2011)
  • Author(s): Yamasaki, M.; Miyazaki, T.; Azechi, H., et al
  • Journal Title: Journal of Neuroscience Volume: 31(9) Issue: 9 Pages: 3362-3374
  • DOI: 10.1523/jneurosci.5601-10.2011
  • Peer Reviewed
• [Journal Article] In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling (2011)
  • Author(s): S.Nishimura
  • Journal Title: Blood Volume: 119 Issue: 8 Pages: 128-131
  • DOI: 10.1182/blood-2011-09-381400
  • Peer Reviewed
• [Journal Article] Glutamate Receptor δ2 Is Essential for Input Pathway-Dependent Regulation of Synaptic AMPAR Contents in Cerebellar Purkinje Cells (2011)
  • Author(s): Yamasaki, M
  • Journal Title: The Journal of Neuroscience Volume: 31 Pages: 3362-3374
  • Peer Reviewed
• [Journal Article] Dynamic distribution of muscle-specific calpain in mice has a key role in physical-stress adaptation and is impaired in muscular dystrophy. (2010)
  • Author(s): Ojima K, Kawabata Y, Nakao H, Nakao K, Doi N, Kitamura F, Ono Y, HataS, Suzuki H, Kawahara H, Bogomolovas J,Will C, Ottenheijm C, LabeitS, Granzier H, Toyama-Sorimachi N, Sorimachi M, Suzuki K, Maeda T, Abe K, Aiba A, Sorimachi H
  • Journal Title: J Clin Invest Volume: 120 Issue: 8 Pages: 2672-2683
  • DOI: 10.1172/jci40658
  • Peer Reviewed
• [Journal Article] Crucial role of the small GTPase Rac1 in insulin-stimulated translocation of glucose transport 4 to the mouse skeletal muscle sarcolema. (2010)
  • Author(s): Ueda S, Kitazawa S, Ishida K, Nishikawa Y, Matsui M, Matsumoto H, Aoki T, Nozaki S, Takeda T, Tamori Y, Aiba A, Kahn CR, Kataoka T, Satoh T
  • Journal Title: TheFASEB Journal Volume: 24 Issue: 7 Pages: 2254-2261
  • DOI: 10.1096/fj.09-137380
  • Peer Reviewed
• [Journal Article] Sequential arrival and graded secretion of Sema3F by olfactory neuron axons specify map topography at the bulb. (2010)
  • Author(s): Takeuchi H, Inokuchi K, Aoki M, Suto F, Tsuboi A, Matsuda I, Suzuki M, Aiba A, Serizawa S, Yoshihara Y, Fujisawa H, Sakano H
  • Journal Title: Cell Volume: 141 Issue: 6 Pages: 1056-1067
  • DOI: 10.1016/j.cell.2010.04.041
  • Peer Reviewed
• [Journal Article] Sequential Arrival and Graded Secretion of Sema3F by Olfactory Neuron Axons Specify Map Topography at the Bulb (2010)
  • Author(s): Takeuchi, H
  • Journal Title: Cell Volume: 141 Pages: 1056-1067
  • Peer Reviewed
• [Journal Article] Crucial role of the small GTPase Raci in insulin-stimulated translocation of glucose transporter 4 to the mouse skeletal muscle sarcolemma (2010)
  • Author(s): Ueda, S
  • Journal Title: The FASEB Journal Volume: 24 Pages: 2254-2261
  • Peer Reviewed
• [Journal Article] Dynamic distribution of muscle-specific calpain in mice has a key role in physical-stress adaptation and is impaired in muscular dystrophy (2010)
  • Author(s): Ojima, K
  • Journal Title: The Journal of Clinical Investigation Volume: 120 Pages: 2672-2683
  • Peer Reviewed
• [Presentation] 中枢神経系において恒常的活性化型mTORを発現するマウスの作製と解析 (2012)
  • Author(s): 饗場 篤
  • Organizer: 日本分子生物学会
  • Place of Presentation: 福岡国際会議場(福岡県)
  • Year and Date: 2012-12-13
• [Presentation] 中枢神経系において恒常的活性化型mTORを発現するマウスの作製と解析 (2012)
  • Author(s): 饗場 篤
  • Organizer: 日本分子生物学会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] Genetic dissection of mGluR1 function in cerebellar Purkinje cells (2011)
  • Author(s): Aiba A
  • Organizer: 7th International Meeting on Metabotropic Glutamate Receptors
  • Place of Presentation: Grande Albergo Capotaormina (Italy)
  • Year and Date: 2011-10-03
• [Presentation] Genetic dissection of mGluR1 function in cerebellar Purkinje cells (2011)
  • Author(s): Aiba, A
  • Organizer: 7th International Meeting on Metabotropic Glutamate Receptors
  • Place of Presentation: Grande Albergo Capotaormina (Italy)(招待講演)
  • Year and Date: 2011-10-03
• [Presentation] mTORC1の恒常的活性化は筋重量の低下を引き起こす (2010)
  • Author(s): 饗場 篤
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸ポートピアホテル(兵庫県)
  • Year and Date: 2010-12-10
• [Presentation] mTORC1の恒常的活性化は筋重量の低下を引き起こす (2010)
  • Author(s): 饗場篤
  • Organizer: 日本分子生物学会第33回年会
  • Place of Presentation: 神戸ボートピアホテル(兵庫県神戸市)
  • Year and Date: 2010-12-10
• [Presentation] ERKは歯状回顆粒細胞の生存に必要である (2010)
  • Author(s): 原田武志
  • Organizer: 日本神経科学学会
  • Place of Presentation: 神戸コンベンションセンター(兵庫県)
  • Year and Date: 2010-09-03
• [Presentation] ERKは歯状回顆粒細胞の生存に必要である (2010)
  • Author(s): 原田武志
  • Organizer: 日本神経科学学会第33回日本神経科学大会
  • 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: 2010-09-03
• [Book] 「mTORシグナルによる脳機能の調節と破綻」細胞工学 (2012)
  • Author(s): 葛西秀俊,饗場篤
  • Publisher: 学研メディカル秀潤社
• [Remarks]
  • URL: http://lar.cdbim.m.u-tokyo.ac.jp/index.html
• [Remarks] 東京大学大学院医学系研究科疾患生命工学センター動物資源学部門ホームページ
  • URL: http://lar.cdbim.m.u-tokyo.ac.jp/index.html