Pathological study of higher brain dysfunction as a neurological outcome in extremely preterm infants

• Project/Area Number: 21591425
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: DEGUCHI Kimiko 独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第二部, 研究生 (50227542)
• Co-Investigator(Kenkyū-buntansha): INOUE Ken 独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第二部, 室長 (30392418) ; KUBO Kenichirou 慶應義塾大学, 医学部, 助教 (20348791)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 未熟児医学 / 神経幹細胞 / 高次脳機能障害 / 神経科学 / 脳神経疾患 / 動物モデル / 脳・神経 / 病理学

Research Abstract

Recently, higher brain dysfunction including hyperactivity and learning disability have been highlighted as neurological outcome of the extremely preterm infants. We hypothesized that the brain ischemia in the extremely preterm infants may result in injuries to the neurons migrating to cortex, subsequently damaging the developing cerebral cortex and causing higher brain dysfunction. In this study, we sought to establish a mouse model for prenatal ischemic brain injuries and delineated the cellular pathological basis for the higher brain dysfunction in extremely preterm infants.

Research Products

• [Journal Article] Effect of curcumin in a mouse model of Pelizaeus-Merzbacher disease (2012)
  • Author(s): Yu L-H, Morimura T, Numata Y, Yamamoto R, Inoue N, Antalfy B, Goto Y, Deguchi K, Osaka H, Inoue K.
  • Journal Title: Mol Genet Metab Volume: 106 Issue: 1 Pages: 108-114
  • DOI: 10.1016/j.ymgme.2012.02.016
  • Peer Reviewed
• [Journal Article] 小坂仁先天性大脳白質形成不全症: Pelizaeus-Merzbacher病とその類縁疾患 (2011)
  • Author(s): 井上健,岩城明子,黒澤健司,高梨潤一,出口貴美子,山本俊至, 小坂 仁
  • Journal Title: 脳と発達 Volume: 43(6) Pages: 435-442
  • Peer Reviewed
• [Journal Article] GABAergic precursor transplantation into the prefrontal cortex prevents phencyclidineinduced cognitive deficits (2011)
  • Author(s): Tanaka DH, Toriumi K, Kubo K, Nabeshima T, Nakajima K
  • Journal Title: J Neurosci Volume: 31 Issue: 40 Pages: 14116-25
  • DOI: 10.1523/jneurosci.2786-11.2011
  • Peer Reviewed
• [Journal Article] The outermost region of the developing cortical plate is crucial for both the switch of the radial migration mode and the Dab1-dependent "inside-out" lamination in the neocortex (2011)
  • Author(s): Sekine K, Honda T, Kawauchi T, Kubo K, Nakajima K
  • Journal Title: J Neurosci Volume: 31 Issue: 25 Pages: 9426-39
  • DOI: 10.1523/jneurosci.0650-11.2011
  • Peer Reviewed
• [Journal Article] Disrupted-in-Schizophrenia-1(Disc1) is necessary for migration of the pyramidal neurons during mouse hippocampal development (2011)
  • Author(s): Tomita K, Kubo K, Ishii K, Nakajima K
  • Journal Title: Hum Mol Genet Volume: 20 Issue: 14 Pages: 2834-45
  • DOI: 10.1093/hmg/ddr194
  • Peer Reviewed
• [Journal Article] Reelin inhibits migration of sympathetic preganglionic neurons in the spinal cord of the chick (2011)
  • Author(s): Yip YP, Zhou G, Kubo K, Nakajima K, Yip JW
  • Journal Title: J Comp Neurol Volume: 519(10) Issue: 10 Pages: 1970-8
  • DOI: 10.1002/cne.22616
  • Peer Reviewed
• [Journal Article] DISC1-dependent switch from progenitor proliferation to migration in the developing cortex (2011)
  • Author(s): Ishizuka K, Kamiya A, Oh EC, Kanki H, Seshadri S, Robinson JF, Murdoch H, Dunlop AJ, Kubo K, Furukori K, Huang B, Zeledon M, Hayashi-Takagi A, Okano H, Nakajima K, Houslay MD, Katsanis N, Sawa A
  • Journal Title: Nature Volume: 473(7345) Issue: 7345 Pages: 92-6
  • DOI: 10.1038/nature09859
  • Peer Reviewed
• [Journal Article] 先天性大脳白質形成不全症:Pelizaeus-Merzbacher病とその類縁疾患 (2011)
  • Author(s): 井上健, 他6名
  • Journal Title: 脳と発達(総説) Volume: 43 Pages: 435-442
  • NAID: 10030290993
  • Peer Reviewed
• [Journal Article] Ectopic Reelin induces neuronal aggregation with a normal birthdate-dependent "inside-out" alignment in the developing neocortex (2010)
  • Author(s): Kubo K, Honda T, Tomita K, Sekine K, Ishii K, Uto A, Kobayashi K, Tabata H, Nakajima K
  • Journal Title: J. Neurosci Volume: 30 Issue: 33 Pages: 10953-66
  • DOI: 10.1523/jneurosci.0486-10.2010
  • Peer Reviewed
• [Journal Article] Migration defects by DISC1 knockdown in C57BL/6, 129X1/SvJ, and ICR strains via in utero gene transfer and virus-mediated RNAi (2010)
  • Author(s): Kubo K, Tomita K, Uto A, Kuroda K, Seshadri S, Cohen JS, Kaibuchi K, Kamiya A, Nakajima K
  • Journal Title: Biochem Biophys Res Commun Volume: 400 Issue: 4 Pages: 631-7
  • DOI: 10.1016/j.bbrc.2010.08.117
  • Peer Reviewed
• [Journal Article] Ectopic Reelin induces neuronal aggregation with a normal birthdate-dependent "inside-out" alignment in the developing neocortex (2010)
  • Author(s): Kubo K, Honda T, Tomita K, Sekine K, Ishii K, Uto A, Kobayashi K, Tabata H, Nakajima K
  • Journal Title: J.Neurosci. Volume: 30(33) Pages: 10953-10966
  • Peer Reviewed
• [Journal Article] Migration defects by DISC1 knockdown in C57BL/6, 129X1/SvJ, and ICR strains via in utero gene transfer and virus-mediated RNAi (2010)
  • Author(s): Kubo K, Tomita K, Uto A, Kuroda K, Seshadri S, Cohen JS, Kaibuchi K, Kamiya A, Nakajima K
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 400(4) Pages: 631-637
  • Peer Reviewed
• [Presentation] 新たな超早産児の虚血性脳傷害モデルマウスを用いた解析(続報) (2011)
  • Author(s): 出口貴美子、久保健一郎、仲島一範、井上健
  • Organizer: 第53回日本小児神経学会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2011-05-28
• [Presentation] 新たな超早産児の虚血性脳障害のモデルマウスの解析:神経前駆細胞の移動障害 (2010)
  • Author(s): 出口貴美子、久保健一郎、仲嶋一範、井上健
  • Organizer: 第55回日本未熟児新生児学会
  • Place of Presentation: 神戸コンベンションセンター、神戸
  • Year and Date: 2010-10-10
• [Presentation] Abnormal neuronal migration with ischemic brain injuries may cause cognitive dysfunction in extremely preterm infants (2010)
  • Author(s): K Deguchi, K Kubo, DL Armstrong, K Nakajima, K Inoue
  • Organizer: 18th Biennial Meeting of the International Society for Development Neuroscience
  • Place of Presentation: Estoril, Portugal
  • Year and Date: 2010-06-08
• [Presentation] Abnormal neuronal migration with ischemic brain injuries may cause cognitive dysfunction in extremely preterm infants. (2010)
  • Author(s): K Deguchi, K Kubo, DL Armstrong, K Nakajima, K Inoue.
  • Organizer: 18th Biennial Meeting of the International Society for Development Neuroscience
  • Place of Presentation: Estoril Convention Centre, Estoril, Portugal
  • Year and Date: 2010-06-08
• [Presentation] 周産期脳障害による高次脳機能障害のマウスモデルの開発 (2010)
  • Author(s): 出口貴美子、久保健一郎、仲嶋一範、井上健
  • Organizer: 第52回日本小児神経学会総会
  • Place of Presentation: 福岡国際会議場、福岡
• [Presentation] 大脳皮質発生におけるリーリン分子の機能の再解析 (2010)
  • Author(s): 久保健一郎、本田岳夫、関根克敏、石井一裕、富田憲司、田畑秀典、仲嶋一範
  • Organizer: 第33回日本神経科学大会・第53回日本神経化学会大会・第20回日本神経回路学会大会合同大会(Neuro2010)
  • Place of Presentation: 神戸コンベンションセンター、神戸
• [Presentation] 大脳皮質発生におけるリーリン分子の機能の再解析 (2010)
  • Author(s): 久保健一郎、本田岳夫、関根克敏、石井一裕、富田憲司、田畑秀典、仲嶋一範
  • Organizer: 第33回日本神経科学大会・第53回日本神経化学会大会・第20回日本神経回路学会大会合同大会 (Neuro2010)
  • Place of Presentation: 神戸コンベンションセンター、神戸