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A study on synaptic transmission system in mental retardation.

Research Project

Project/Area Number 01044157
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionNational Institute of Neuroscience, National center of Neurology and Psychiatry

Principal Investigator

TAKASHIMA Sachio  Division of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry., 神経研究所・疾病研究第2部, 部長 (70038743)

Co-Investigator(Kenkyū-buntansha) MITO Takashi  Division of Mental Retardation and Birth Defect Research, National Institute of, 神経センター・神経研究・疾病研究第2部, 室長 (00166068)
KONOMI Hiroshi  Division of Mental Retardation and Birth Defect Research, National Institute of, 神経センター・神経研究・疾病研究第2部, 室長 (00186719)
BECKER L. E.  Division of Neuropathology, The Hospital for Sick Children, University of Toront, 小児病院・神経病理学, 教授
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1991: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1990: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1989: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywordssynapsis / mental retardation / neuron / peroxisome / catecholamine / brain anomaly / down syndrome / 神経伝達物質 / 中枢神経
Research Abstract

1. Synaptic dysgenesis in neuronal migration disorders.
Neurons proliferate, migrate, settele and grow in the fetal period. Immunohistochemical and Golgi studies were performed on 6 patients with hemimegalencephaly. Immunohistochemical staining demonstrated glial, neuronal, and myelin heterotopia in the leptomeninges, cortex, white matter with glial fibrillary acidic protein, myelin basic protein, and synaptophysin antibodies. Golgi studies revealed small and deformed neurons in the superficial layers around abnormal sulci, and hypertrophic neurons with an increased number of dendrites and spines in the deeper cortex. The coexistence of a cell migration disorder, proliferation, and hypertrophy in each patient may imply a growth factor disturbance that controls cell proliferation. Immunohistochemical study on the brains with lissencephaly suggested that the sparsely cellular layer may correspond to the molecular layer and white matter in normal brain. Neurons with forming myelin sheaths … More in the superficial cellular layer regularly penetrate the surface of the molecular layer, forming arrested cortical columns in the deep cellular layer. In the cases of Zellweger syndrome, G opigi studies revealed abnormal morphogenesis and delayed maturation in intrauterine development, and the imminohistochemistry suggested myelination disturbance in perinatal period.
In atypical phenylketonuria and maple syrup urine diselse there were irregular neuronal arrangement and dendritic spine reduction. This abnormalities may occur at settling of neurons, which may be influenced by metabolic disorder before birth.
2. Developmental abnormalities of catecholaminenrgic neurons in the brainstem.
The catecholaminergic neurons in the medullary dorsal and solitary nuclei of the brains tem appear to play an important role in respiratory control and those in ventrolateral medulla (VLM) in chemoreception and cardiovascular control. In immunohistochemistry of tyrosine hydroxylase (TH) and Golgi study, TH-positive neurons were identified in the VLM at 14 weeks of gestation, and the size of cell body and length of dendrites increased with maturation. In controls the number of dendritic spines increased with increasing gestational age, but decreased after 40 weeks of gestation. However, in SIDS, dendritic spines in VLM as well as in the reticular formation and vagal nuclei persisted compared to controls. Substance P-positive nervefibers were increased in the trigeminal nerve of SIDS. These observations suggest that a delay in maturation of medullary neurons in SIDS thoght to be responsible for cardiorespiratory control.
3.21 chromosome, mental retardation and precocious aging.
Dendritic soines in the cerebral cortex rapidly increase in controls, but poorly increase in childhood and more markedly decrease in elderly adults of Down syndrome. Immunohistochemistry of amyloid demonstrated early appearance of amylold deposition in plaques and vessels, which are related to precocious dementia in Down syndrome. Furthermore, we made antibodies against membrane protein which genes were coded on chromosome 21, and immunohistochemistry revealed that they appeared earlier in the temporal cortex than in the frontal cortex of Down syndrome. In addition, immunohistochemistry of S-100 showed an increase of S-100 in the temporal cortex in Down syndrome, compared with controls. This result may be related to delayed synaptic development and mental retardation. Thus, several pathogenetic factors may be related to retardation of synaptogenesis and mentality in Down syndrome. Less

Report

(2 results)
  • 1991 Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (46 results)

All Other

All Publications (46 results)

  • [Publications] Takashima S,Becker LE,et al: "A aberrant neuronal development in hemimegalencephaly:Immunohistochemical and Golgi studies." Pediatr Neurol. 7. 275-280 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Mito T,Takashima S,et al: "Immunohistochemical study of the vasculature in the developing brain." Pediatr Neurol. 7. 8-12 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S,Becker LE,et al: "A neuropathology and Golgi study of phynylketonuria." Pediatr Pathol. 11. 771-779 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S,Becker LE,et al: "Cortical cytoarchitectural and immunohistochemical studies on Zellweger syndrome." Brain Dev. 13. 158-162 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Houdou S,Takashima S,et al: "Developmental immunohistochemistry of catalase in the human brain." Brain Res. 556. 267-270 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S,Becker LE: "Delayed dendritic development of catecholaminergic neurons in the ventrolateral medulla of children who died of sudden infact death syndrome." Neuropediatrics. 22. 97-99 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Becker LE,Mito T,Takashima S,Onodera K.: "Growth and Development of the Down syndrome.The morphogenesis of Down syndrome." WilyーLiss,Inc., 133-152 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S,Becker LE: "Development of catecholaminergic neurons and substance Pーsubstance Pーpositive nerve fibers in the brainstem of victims of sudden infant death syndrome." Proceed.of World Congr.of Sleep Apnea and Rhonch,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, Becker LE, et al: "A aberrant neuronal development in hemimegalencephaly : Immunohistochemical and Golgi studies." Pediatr Neurol. 7. 275-280 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Mito T, Takashima S, et al: "Immunohistochemical study of the vasculature in the developing brain." Pediatr Neurol. 7. 8-12 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tkakashima S, Becker LE, et al: "A neuropathology and Golgi study of phenylketonuria." Pediatr Pathol. 11. 771-779 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, Beckar LE, et al: "Cortical cytoarchitectural and immunohistochemical studies on Zellweger syndrome." Brain Dev. 13. 158-162 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Houdou S, Takashima S, et al: "Developmental immunohistochemistry of catalase in the human brain." Brain Res. 556. 267-270 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, Becker LE: "Delayed dendritic development of catecholaminergic neurons in the ventrolateral medulla of children who died of sudden infant death syndrome." Neuropediatrics. 22. 97-99 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Koyama K, Takashima S, et al: "The effects of prostaglandin E1 and nicardipine on cerebral blood flow, blood volume and oxygenation in young rabbits." Brain Dev. 13. 32-35 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto K, Takashima S, et al: "Hypocarbia and a pathogenetic factor in pontosubicular necrosis." Brain Dev. 13. 155-157 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hasegawa M, Takashima S, et al: "Continuous comparison of cerebral blood flow velocity and volume on hypoxia." Brain Dev. 13. 433-437 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, Becker LE: "Dendritic development of motor neurons in the cervical anterior horn and hypoglossal nucleus of normal infants and victims of SIDS." Neuropediatrics. 21. 433-437 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, et al: "Developmental and aging changes in the expression patterns of beta-amyloid in the brains of normal and Down syndrome Cases." Brain Dev. 12. 367-271 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, et al: "Immunohistochemistry of superoxide dismutase-1 in developing human brain." Brain Dev. 12. 211-213 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, Onodera K, et al: "Immunohistochemistry of membrane proteins in the brain coded by a gene on human chromosome 21." Devel Brain Res. 53. 295-298 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Mito T, Takashima S, et al: "Response on near-infrared spectroscopy and of cerebral blood flow to hypoxemia induced by N2 and CO2 in young rabbits." Brain Dev.12. 408-411 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Houdou S, Takashima S. et al: "Structure in lissencephaly detarmined by immunohistochemical staining." Pediatr Neurol. 6. 402-406 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, et al: "Dendrites, dementia and the Down syndrome." Brain Dev. 2. 131-133 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Mito T, Becker LE: "Developmental changes of S-100 protein and glial fibrillary acidic protein in the brain Down syndrome." Neuropediatrics.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Mito T, Becker LE: "Down syndrome and structural defects of carotid arteries : A possible relationship to Moyamoya disease." Brain Dev.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Koyama K, Takashima S, et al: "The effects of prostaglandin E1 and nicardipine on cerebral blood flow, blood voluma and oxygenation in young rabbits." Brain Dev. 13. 32-35 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto K, Takashima S, et al: "Hypocarbia and a pathogenetic factor in pontosubicular necrosis." Brain Dev. 13. 155-157 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hasegawa M, Takashima S, et al: "Continuous comparison of cerebral blood flow velocity and volume on hypoxia." Brain Dev. 13. 433-437 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, Becker LE: "Dendritic development of motor neurons in the cervical anterior horn and hypoglossal nucleus of normal infants and victims of SIDS." Neuropediatrics. 21. 433-437 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, et al: "Developmental and aging changes in the expression patterns of beta-amyloid in the brains of normal and Down syndrome Cases." Brain Dev. 12. 367-271 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, et al: "Immunohistochemistry of superoxide dismutase-1 in developing human brain." Brain Dev. 12. 211-213 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, Onodera K, et al: "Immunohistochemistry of membrane proteins in the brain coded by a gene on human chromosome 21." Devel Brain Res. 53. 295-298 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Mito T, Takashima S, et al: "Respones on near-infrared spectroscopy and of cerebral blood flow to hypoxemia induced by N2 and CO2 in young rabbits." Brain Dev. 12. 408-411 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Houdou S, Takashima S, et al: "Structure in lissencephaly detarmined by immunohistochemical staining." Pediatr Neurol. 6. 402-406 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, et al: "Dendrites, dementia and the Down Syndrome." Brain Dev. 2. 131-133 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Mito T, Becker LE: "Developmental changes of S-100 protein and glial fibrillary acidic protein in the brain in Down syndrome." Neuropediatrics.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Mito T, Becker LE: "Down syndrome and structural defects of carotid arteries : A possible relationship to Moyamoya disease."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Becker LE, Mito T, Takashima S, Onodera K.: Wily-Liss, Inc.Growth and Development of the Down syndrome. The morphogenesis of Down syndrome., 133-152 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashima S, Becker Le: Proceed. of World Congr. of Sleep Apnea and Rhonch. Development of catecholaminergic neurons and substance P-substance P-positive nerve fibers in the brainstem of victims of sudden infant death syndrome.,

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 高嶋 幸男: "Dendritic development of motor neurons in the cervical anterior horn and hypoglossal nucleus of normal infants and victims of SIDS." Neuropediatrics. 21. 24-26 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] 高嶋 幸男: "Developmental and aging changes in the expression patterns of betaーamyloid in the brains of normal and Down syndrome cases." Brain Dev. 12. 367-371 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 高嶋 幸男: "Immunohistochemistry of superoxide dismutaseー1 in developing human brain." Brain Dev. 12. 211-213 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 高嶋 幸男: "Immunohistochemistry of membrane proteins in the brain coded by a gene on human chromosome 21." Devlop Brain Res. 53. 295-298 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 高嶋 幸男: "Response on nearーinfrared spectroscopy and of cerebral blood flow to hypoxemia induced by N2 and CO2 in young rabbits." Brain Dev. 12. 408-411 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 高嶋 幸男: "Structure in lissencephaly detarmined by immunohistochemical staining." Pediat Neur. 6. 402-406 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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