Live-imaging of synapses in the model system of neurodevelopmental disorders

• Project/Area Number: 15K15399
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• Principal Investigator: Nagata Koh-ichi 愛知県心身障害者コロニー発達障害研究所, 神経制御学部, 部長 (50252143)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: シナプス / ライブイメージング / 自閉性障害 / 知的障害 / 神経細胞 / 海馬神経細胞 / ライブイメージ / スパイン / イメージング / 大脳皮質

Outline of Final Research Achievements

Functional and structural defects in Synapses are essential for the pathophysiology of autism-spectrum disorder (ASD) and intellectual disability (ID). In the present study, we performed in vitro live-imaging analyses of synapses in cultures mouse hippocampal neurons.Especially, we observed synaptic structure from the points of 1) spine formation, 2) temporal change of spine morphology and 3) spine density. By knockdown of ASD- or ID-related genes such as small GTPases, we clarified the possible involvement of gene abnormalities in the pathophysiology of ASD and ID. We also tried to set up the experimental system for in vivo analyses of spine dynamics.

Research Products

• [Int'l Joint Research] Dept. of Pharmacology, Yale University(米国)
• [Int'l Joint Research] Pohang University(韓国)
• [Int'l Joint Research] Duke-National University of Singapore(Singapore)
• [Journal Article] Prdm16 is crucial for progression of the multipolar phase during neural differentiation of the developing neocortex. (2017)
  • Author(s): Inoue M, Iwai R, Tabata H, Konno D, Komabayashi-Suzuki M, Watanabe C, Iwanari H, Mochizuki Y, Hamakubo T, Matsuzaki F, Nagata K-I, Mizutani K-I
  • Journal Title: Development Volume: 144 Issue: 3 Pages: 385-399
  • DOI: 10.1242/dev.136382
  • Peer Reviewed
• [Journal Article] Dnmt1-dependent Chk1 pathway suppression is protective against neuron division (2017)
  • Author(s): Oshikawa Mio、Okada Kei、Tabata Hidenori、Nagata Koh-ichi、Ajioka Itsuki
  • Journal Title: Development Volume: 144 Issue: 18 Pages: 3303-3314
  • DOI: 10.1242/dev.154013
  • Peer Reviewed
• [Journal Article] Role of a circadian-relevant gene NR1D1 in brain development: possible involvement in the pathophysiology of autism spectrum disorders. (2017)
  • Author(s): Goto, M., Mizuno, M., Matsumoto, A., Yang, Z., Jimbo, E.F., Tabata, H., Yamagata, T., Nagata, K.-I.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 43945-43945
  • DOI: 10.1038/srep43945
  • Peer Reviewed / Open Access
• [Journal Article] MUNC18-1 gene abnormalities are involved in neurodevelopmental disorders through defective cortical architecture during brain development (2017)
  • Author(s): Hamada Nanako、Iwamoto Ikuko、Tabata Hidenori、Nagata Koh-ichi
  • Journal Title: Acta Neuropathologica Communications Volume: 5 Issue: 1 Pages: 92-92
  • DOI: 10.1186/s40478-017-0498-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of a heterotrimeric G-protein, Gi2, in the corticogenesis: possible involvement in periventricular nodular heterotopia and intellectual disability. (2016)
  • Author(s): Hamada, N., Negishi, Y., Mizuno, M., Miya, F., Hattori, A., Okamoto, N., Kato, M., Tsunoda, T., Yamasaki, M., Kanemura, Y., Kosaki, K., Tabata, H., Saitoh, S., Nagata, K.-I.
  • Journal Title: J. Neurochem. Volume: 140 Issue: 1 Pages: 82-95
  • DOI: 10.1111/jnc.13878
  • Peer Reviewed
• [Journal Article] Role of Class III phosphoinositide 3-kinase in the brain development: possible involvement in specific learning disorders. (2016)
  • Author(s): Inaguma Y, Matsumoto A, Noda M, Tabata H, Maeda A, Goto M, Usui D, Jimbo EF, Kikkawa K, Ohtsuki M, Momoi MY, Osaka H, Yamagata T, Nagata KI
  • Journal Title: J Neurochem Volume: 139 Issue: 2 Pages: 245-55
  • DOI: 10.1111/jnc.13832
  • Peer Reviewed
• [Journal Article] Schizophrenia susceptibility gene product dysbindin-1 regulates the homeostasis of cyclin D1. (2016)
  • Author(s): Ito H, Morishita R, Nagata K
  • Journal Title: Biochim Biophys Acta Volume: 1862 Issue: 8 Pages: 1383-1391
  • DOI: 10.1016/j.bbadis.2016.04.016
  • Peer Reviewed
• [Journal Article] Essential role of the nuclear isoform of RBFOX1, a candidate gene for autism spectrum disorders, in the brain development. (2016)
  • Author(s): Hamada N, Ito H, Nishijo T, Iwamoto I, Morishita R, Tabata H, Momiyama T, Nagata K-I
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 30805-30805
  • DOI: 10.1038/srep30805
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of BDNF exocytosis and GABAergic interneuron synapse by the schizophrenia susceptibility gene dysbindin-1. (2016)
  • Author(s): Yuan Q, Yang F, Xiao Y, Tan S, Husain N, Ren M, Hu Z, Martinowich K, Ng J S, Kim P J, Han W, Nagata K, Weinberger DR, H. Je S
  • Journal Title: Biol. Psychiatry Volume: 80 Issue: 4 Pages: 312-322
  • DOI: 10.1016/j.biopsych.2015.08.019
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Morphological characterization of Class III phosphoinositide 3-kinase during mouse brain development. (2016)
  • Author(s): Inaguma Y, Ito H, Iwamoto I, Matsumoto A, Yamagata T, Tabata H, Nagata K-I
  • Journal Title: Med Mol Morphol Volume: 49 Issue: 1 Pages: 28-33
  • DOI: 10.1007/s00795-015-0116-1
  • Peer Reviewed / Open Access
• [Journal Article] Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients. (2015)
  • Author(s): Yang Z, Matsumoto A, Nakayama K, Jimbo EF, Kojima K, Nagata KI, et al.
  • Journal Title: Brain Dev. Volume: 15 Issue: 1 Pages: 91-9
  • DOI: 10.1016/j.braindev.2015.04.006
  • Peer Reviewed / Open Access
• [Journal Article] Role of the cytoplasmic isoform of RBFOX1/A2BP1 in establishing the architecture of the developing cerebral cortex. (2015)
  • Author(s): Hamada N, Ito H, Iwamoto I, Morishita R, Tabata H, Nagata K-I
  • Journal Title: Molecular Autism Volume: 6 Issue: 1 Pages: 56-56
  • DOI: 10.1186/s13229-015-0049-5
  • Peer Reviewed / Open Access
• [Journal Article] Disrupted-in-schizophrenia 1 (DISC1) regulates dysbindin function by enhancing its stability. (2015)
  • Author(s): Lee S-A, Kim S-M, Suh B K, Sun H-Y, Park Y-U, Hong J-H, Park C, Nguyen M D, Nagata K, Yoo J-Y, Park S K
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 11 Pages: 7087-7096
  • DOI: 10.1074/jbc.m114.614750
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Comprehensive analyses of causative genes for ASD with in utero electropolation technique. (2017)
  • Author(s): Nagata K
  • Organizer: International Symposium on Autism 2017
• [Presentation] Comprehensive analyses of RBFOX1, a causative gene for neurodevelopmental and psychiatric diseases, in the brain development. (2016)
  • Author(s): Nagata K
  • Organizer: The 14th Meeting of the Asian-Pacific Society for Neurochemistry
  • Place of Presentation: Kuala Lumpur, Malaysia
  • Year and Date: 2016-08-27
  • Int'l Joint Research / Invited
• [Presentation] Rbfox1, an autism causal gene, plays an essential role in cortical development. (2015)
  • Author(s): 浜田奈々子，伊東秀記，田畑秀典，永田浩一
  • Organizer: 日本神経化学会大会シンポジウム
  • Place of Presentation: 大宮
  • Year and Date: 2015-09-10
  • Invited
• [Presentation] Comprehensive approach to understand physiological role of SIL1, a gene causing intellectual disability. (2015)
  • Author(s): Nagata K
  • Organizer: 25th ISN meeting Symposium
  • Place of Presentation: Cairns
  • Year and Date: 2015-08-23
  • Int'l Joint Research / Invited