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胎児・新生児脳組織バンキングによる脳障害の分子発生病理学的研究

Research Project

Project/Area Number 10470221
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

高嶋 幸男  精神神経セ (70038743)

Co-Investigator(Kenkyū-buntansha) 大湯 淳功  国立精神, 神経センター・疾病研究第2部, 研究員
伊藤 雅之  国立精神, 神経センター・疾病研究第2部, 研究員 (50243407)
岡 明  国立精神, 神経センター・疾病研究第2部, 研究員 (00251273)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥3,100,000 (Direct Cost: ¥3,100,000)
Keywords脳バンク / 新生児脳障害 / 乳幼児突然死症候群 / 小児遺伝性神経疾患 / グルタミン酸受容体 / ドーパミン受容体
Research Abstract

1. 発達期脳組織バンキングのシステム化。
承諾を得た胎児・新生児・小児の剖検に際し、脳検索例は1,200例をこし、脳および主要臓器の一部の新鮮生組織の凍結保存例は、その約4分の1と増加した。各施設の剖検例は減少しているために、本システムは長期継続したい。生化学的、分子生物学的ならびに組織化学的な協同研究への利用も増加しつつある。
2. 発達期脳の生化学的、分子生物学的ならびに免疫組織化学的研究。
周産期の低酸素性虚血性脳障害の発生に関与する因子は多く、血管、フリーラジカル、グルタミン・ドーパミン酸受容体、一酸化窒素、アポトーシス関連因子を発達的免疫組織化学的にみて、周産期の脳の特徴を明らかにした。これに基づいて、低酸素性虚血性脳障害例の病変を経時的に調べ、小脳で特有のグルタミン酸トランスポータ(EAAT4,GKLST)が細胞障害の早期から作用していること、基底核壊死ではドーパミンD2受容体が神経細胞の変性と可塑性に関与していること、脳室周囲白質軟化では血管内皮成長因子が壊死巣修復に作用していることが分かった。また、乳幼児突然死症候群の脳が集積され、検索され、延髄呼吸調節中枢のカテコラミンやセロトニン神経細胞の異常が発見され、更に上位中枢の異常があることが分かった。最近、遺伝性の小児神経疾患の遺伝子が発見され、病態を分子病理学的に検討し、滑脳症(Miller-Dieker症候群など)、神経皮膚症候群(結節性硬化症、Recklinghausen病)、ataxiateleangiectasiaや皮質形成異常の特異性が明らかになってきた。このように、脳組織バンキングの資料は有効に活用されており、今後の病態研究にも活用したい。

Report

(1 results)
  • 1998 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Obonai T,Mizuguchi M,Takashima S: "Developmental and aging changes of Bak expression in the human brain" Brain Research. 783. 167-170 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Obonai T,Yasuhara Y,Nakamura T,Takashima S: "Catecholamine neurons alteration in the brainstem of sudden infant death syndrome victims" Pediatrics. 101. 285-288 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Inage Y.W.,Itoh M,Wada K,Takashima S: "Expression of two glutamate transporters.GLAST and EAAT4,in the human cerebellum:their correlation in development and neonatal hypoxic-ischemic damage" J of Neuropathology and Experimental Neurology. 57. 554-562 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Meng S.Z,Isumi H,Takashima S: "Neuropathological characteristics and alteration of the dopamine D_2 receptor in hypoxic-ischemic basal ganglia necrosis" Brain & Dev. 20. 98-104 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kato M,Mizuguchi M,Hattori S,Nakamura S,Takashima S: "Loss of neurofibromin in the leptomeningeal astroglial heterotopia of NF-1" Pediatr Neurol. 18. 227-230 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oka A,Takashima S: "Expression of the ataxia-telangiectasia gene(ATM)product in human cerebellar neurons during development" Neuroscience Letters. 252. 195-198 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oka A,Kurachi Y,Mizuguchi M,Hayashi M,Takashima S: "Expression of late infantile neuronal ceroid lipofuscinosis(CLN2)gene product in human brains" Neuroscience Letters. 257. 113-115 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takashima S,Mizuguchi M,Arii N: "Neuronal migration disorder:expression of gene products in the neocortex" Neuropathology. 18. 427-432 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ozawa H,Takashima S: "Immunocytochemical Devlopment of transferrin and ferritin immunoreactivity in the human pons and cerebellum" J.of Child Neurology. 13. 59-63 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Obonai T,Mizuguchi M,Takashima S: "Developmental and aging changes of Bak expression in the human brain" Brain Research. 783. 167-170 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Meng S.Z,Obonai T,Takashima S: "A developmental study of the dopamine D2R receptors in the human basal ganglia and thalamus" Harly Human Dev. 51. 23-30 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohyu J,Takashima S: "Developmental characteristics of neuronal nitric oxide synthase(nNOS)immunoreactive neurons in fetal to adolescent human brains" Dev Brain Res. 110. 193-202 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyawaki T,Matsui K,Takashima S: "Developmental characteristics of vessel density in the human fetal and infant brains" Early Human development. 53. 65-72 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Obonai T,Yasuhara Y,Nakamura T,Takashima S: "Catecholamine neurons alteration in the brainstem of sudden infant death syndrome victims" Pediatrics. 101. 285-288 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Obonai T,Takashima S: "In utero brain lesions in SIDS" Pediatr Neurol. 19. 23-25 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Inage Y.W.,Itoh M,Wada K,Takashima S: "Expression of two glutamate transporters,GLAST and EAAT4,in the human cerebellum:their correlation in development and neonatal hypoxic-ischemic damage" J of Neuropathology and Experimental Neurology. 57. 554-562 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Meng S.Z,Isumi H,Takashima S: "Neuropathological characteristics and alteration of the dopamine D_2 receptor in hypoxic-ischemic basal ganglia necrosis" Brain & Dev. 20. 98-104 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohyu J,Takashima S: "Decreased expression of microtubule-associated protein 5(MAP5)in the molecular layer of cerebellum in preterm infants with olivocrebellar lesions" Brain & Dev. 20. 22-26 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Arai Y,Deguchi K,Takashima S: "Vascular endothelial growth factor in brains with periventricular leukomalacia" Pediatric Neurology. 19. 45-49 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kato M,Mizuguchi M,Hattori S,Nakamura S,Takashima S: "Loss of neurofibromin in the leptomeningeal astroglial heterotopia of NF-1" Pediatr Neurol. 18. 227-230 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Isumi H,Takashima S,Ikeda K,Mizuguchi M: "Expression of a 45K subunit of platelet-activating factor acetyl-hydrolase in the developing mouse cerebellum" Anat Embryol. 197. 415-419 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oka A,Takashima S: "Expression of the ataxia-telangiectasia gene(ATM)product in human cerebellar neurons during development" Neuroscience Letters. 252. 195-198 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oka A,Kurachi Y,Mizuguchi M,Hayashi M,Takashima S: "Expression of late infantile neuronal ceroid lipofuscinosis(CLN2)gene product in human brains" Neuroscience Letters. 256. 1-3 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takashima S,Mizuguchi M,Arii N: "Neuronal migration disorder:expression of gene products in the neocortex" Neuropathology. 18. 427-432 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamanouchi H,Jay V,Otsubo H,Kaga M,Becker L.E.,Takashima S: "Early forms of microtubule-associated protein are strongly expressed in cortical dysplasia" Acta Neuropathol. 95. 466-470 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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