Mechanisms and prevention of developmental brain disorders due to prenatal effects of physical agents

物理因素产前影响引起的脑发育障碍的机制和预防

基本信息

  • 批准号:
    04044099
  • 负责人:
  • 金额:
    $ 4.35万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for international Scientific Research
  • 财政年份:
    1992
  • 资助国家:
    日本
  • 起止时间:
    1992 至 1993
  • 项目状态:
    已结题

项目摘要

1. Comparative study of heat-induced teratogenesis in the human and guinea pigHistological studies of human embryos with neural tube defects whose mothers experienced hyperthermic stress early in pregnancy revealed overgrowth, necrosis, vacuolization, rosette formation and cortical derangement in the brain of heated embryos. These histological abnormalities resembled the pathological findings observed in guinea pig fetuses heated in utero. It seems that hyperthermia induces developmental brain abnormalities by common mechanisms in the human and guinea pig. Guinea pigs are born with a rather mature brain and can be a good model of developmental brain disorders in the human.2. Induction of heat-shock proteins and thermotoleranceWhen cultured rat embryos are heated in vitro for 7.5 min at 43゚C, neural tube closure is inhibited. If cultured embryos were preheated by subteratogenic heating conditions (e.g., 42゚C for 10 min), the incidence of malformed embryos decreased, suggesting that rat embryos can acquire thermotolerance by subteratogenic heating.Several specific heat-shock proteins are induced in rat fetal tissues. When rat fetuses were heated in utero, HSP88, 73 and 71 were increased while HSP73 was decreased. The relationship between the induction of heat-shock proteins and thermotolerance is now under study.3. Vertebral transformation induced by prenatal heat stressPregnant mice were heated in utero on day 7, 8 or 9 of gestation and the skeletons of their fetuses were stained and examined. Anterior and posterior transformations of the axial skeleton were induced depending on the timing of heat stress and the degree of heat elevation. Prenatal heat stress may disturb the expression of homeotic genes and cause abnormal differentiation of the somite.The present studies showed that prenatal heat stress can interfere with the development of the brain and produce various developmental brain disorders.
1.对患有神经管缺陷的人类胚胎进行的组织学研究表明,在加热胚胎的大脑中,存在过度生长、坏死、空泡化、玫瑰花结形成和皮质紊乱。这些组织学异常与在子宫内加热的豚鼠胎仔中观察到的病理学结果相似。高温似乎通过人类和豚鼠的共同机制诱导发育性脑异常。豚鼠天生就有相当成熟的大脑,可以成为人类大脑发育障碍的良好模型。热休克蛋白的诱导与热耐受性体外培养的大鼠胚胎在43 ℃下加热7.5分钟,神经管的关闭受到抑制。如果培养的胚胎通过致畸形的加热条件(例如,42 ℃处理10 min),畸形胚胎的发生率降低,提示大鼠胚胎经致畸性加热后可获得热耐受性。胎鼠宫内加热后,HSP88、73、71升高,HSP73降低。热休克蛋白的诱导与耐热性的关系正在研究中.产前热应激诱发的脊椎骨转化将孕鼠于妊娠第7、8或9天在子宫内加热,并对其胎儿骨骼进行染色和检查。中轴骨骼的前后转换取决于热应激的时间和热升高的程度。产前热应激可干扰同源异型基因的表达,导致体节的异常分化,目前的研究表明,产前热应激可干扰脑的发育,导致多种发育性脑疾病。

项目成果

期刊论文数量(15)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Shiota,K.: "Teratothanasia:Natural prenatal scereening of abnormal human conceptuses and the prevalence of various malformations during gestation" Birth Defects:Original Article Series. 29. 183-193 (1993)
Shiota, K.:“畸形死亡:异常人类受孕的自然产前筛查和妊娠期间各种畸形的流行”出生缺陷:原创文章系列。
  • DOI:
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    0
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  • 通讯作者:
Smith,M.S.R., Upfold,J.B., Edwards,M.J., Shiota,K., and Cadwell-Smith,J: "The induction of neural tube defects by maternal hyperthermia : A comparison of the guinea-pig and human" Neuropathology and Applied Neurobiology. 18. 71-80 (1992)
Smith,M.S.R.、Upfold,J.B.、Edwards,M.J.、Shiota,K. 和 Cadwell-Smith,J:“母体高温诱导神经管缺陷:豚鼠和人类的比较”神经病理学和应用神经生物学。
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    0
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  • 通讯作者:
Moore,K.L., Persaud,T.V.N. and Shiota,K.: Saunders (Philadelphia). Color Atlas of Clinical Embryology, (1994)
摩尔,K.L.,佩尔绍德,T.V.N.
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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  • 通讯作者:
Smith, M.S.R.et al.: "The induction of neural tube defects by maternal hyperthermia:a comparison of the guinea-pig and human" Neuropathology and Applied Neurobiology. 18. 71-80 (1992)
Smith, M.S.R.等人:“母体高温诱导神经管缺陷:豚鼠和人类的比较”神经病理学和应用神经生物学。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Smith,M.S.R.,Upfold,J.B.,Edwards,M.J.,Shiota,K.and Cadwell-Smith,J.: "The induction of neural tube defects by maternal hyperthermia:A Comparison of the guinea-pig and human" Neuropathology and Applied Neurobiology. 18. 71-80 (1992)
Smith,M.S.R.、Upfold,J.B.、Edwards,M.J.、Shiota,K. 和 Cadwell-Smith,J.:“母体高温诱导神经管缺陷:豚鼠和人类的比较”神经病理学和应用神经生物学。
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SHIOTA Kohei其他文献

SHIOTA Kohei的其他文献

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{{ truncateString('SHIOTA Kohei', 18)}}的其他基金

Gene-environmental interaction in early morphogenesis of the brain and developmental anomalies due to its disturbance
大脑早期形态发生中的基因-环境相互作用以及由于其干扰而导致的发育异常
  • 批准号:
    19390050
  • 财政年份:
    2007
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Establishing a database of MR microscopic images of human embryos and an educational system for human embryology
建立人类胚胎MR显微图像数据库和人类胚胎学教育系统
  • 批准号:
    13557001
  • 财政年份:
    2001
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Developmental Brain Disorders due to Physical Agents
物理因素引起的脑发育障碍
  • 批准号:
    10044271
  • 财政年份:
    1998
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
Developmental and molecular cell biological study of the mechanisms of limb differentiation
肢体分化机制的发育和分子细胞生物学研究
  • 批准号:
    10470004
  • 财政年份:
    1998
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
Morphological and molecular cell biological study of apoptosis in mammalian morphogenesis
哺乳动物形态发生中细胞凋亡的形态学和分子细胞生物学研究
  • 批准号:
    08457005
  • 财政年份:
    1996
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular Diagnosis of Genic Abnormalities using Human Tissue Materials
使用人体组织材料进行基因异常的分子诊断
  • 批准号:
    07557326
  • 财政年份:
    1995
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Apoptsis in mammalian morphogenesis.
哺乳动物形态发生中的细胞凋亡。
  • 批准号:
    06454140
  • 财政年份:
    1994
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
Development of alternatives to animal experiments with in vitro cultures of undifferentiated embryonic cells and organ primodia
利用未分化胚胎细胞和器官原基的体外培养物开发动物实验的替代方案
  • 批准号:
    05557002
  • 财政年份:
    1993
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for Developmental Scientific Research (B)
Study on the role of epidermal growth factor receptor and protooncogenes in mammalian morphogenesis
表皮生长因子受体和原癌基因在哺乳动物形态发生中的作用研究
  • 批准号:
    04670014
  • 财政年份:
    1992
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Immunohistochemical study on the expression and localization of the epidermal growth factor receptor during morphogenesis
形态发生过程中表皮生长因子受体表达和定位的免疫组织化学研究
  • 批准号:
    02670007
  • 财政年份:
    1990
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

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Subgroup delineation in genetic epilepsies and developmental brain disorders
遗传性癫痫和发育性脑疾病的亚组划分
  • 批准号:
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Mechanisms of disease and treatment in novel metabolic developmental brain disorders
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  • 批准号:
    10712302
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Mechanisms of Disease and Treatment in Novel Metabolic Developmental Brain Disorders
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与突触病理学相关的发育性脑疾病的分子分析
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    9891097
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与突触病理学相关的发育性脑疾病的分子分析
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Thalamocortical circuit defects in developmental brain disorders
发育性脑疾病中的丘脑皮质回路缺陷
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