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Development of drugs for facilitating brain development and memory/learning

Research Project

Project/Area Number 13557086
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Embryonic/Neonatal medicine
Research InstitutionYamaguchi University

Principal Investigator

NAKAMURA Shoji  Yamaguchi Univ. Sch. Med. Professor, 医学部, 教授 (80112051)

Co-Investigator(Kenkyū-buntansha) SAKATA Yoshiyuki  Yamaguchi Univ. Sch. Med. Assistant Professor, 医学部, 講師 (10034927)
OKUYAMA Shigeru  Taisho Pharmaceutical CO., LTD. Business Strategy Division Pharmaceutical Business Group Group Manager, 医薬事業企画部, マネージャー(研究職)
ISHIDA Yoshiyuki  Yamaguchi Univ. Sch. Med. Assistant, 医学部, 助手 (20325210)
LIU Yin  Yamaguchi Univ. Sch. Med. Assistant, 医学部, 助手 (40335724)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2002: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 2001: ¥5,200,000 (Direct Cost: ¥5,200,000)
Keywordsbrain development / DNA tip / memory / learning / prenatal stress / neurotrophic / neurotoxic / Alzheirmer disease / 胎仔脳 / 海馬 / ストレス / 胎生期
Research Abstract

In a previous study, we have found that short-lasting mild prenatal stress (restraint stress to pregnant rats, 30min/day for 3 days from E15 to E17, 30-min stress group) induces neurotrophic effects on morphology of fetal brain neurons, while long-lasting stress (4 hours/day for 3days from E15 to E17, 4-hrs stress group) causes neurotoxic changes. In addition, we have shown that the 30-min stress group reveals significantly better memory and learning performance in the adult offspring. Based on these results, using DNA tips, the present experiments were performed to identify genes which are involved in the facilitation of development of brain neurons and enhanced cognitive performance.
Gene expression in three groups, control, 30-min stress and 4-hrs stress groups was investigated using 3 pieces of DNA tips (Rat Genome U34A, Affymetrix) for each group. The DNA tips used included about 8800 genes. The genes analyzed were receptors (808), channels (187), transporters (138), enzymes (1822), kinases (382), phosphatases (129), and transcription factors (57). The total RNAs extracted from the whole brain and hippocampal tissue of the fetal brains were analyzed. Gene expression was ranked for significance based on replication of data, signal intensity, statistical significance of differences among the three groups. Five to twenty genes that revealed significant increases or decreases in expression in the 30-min stress and 4-hrs stress group as compared to the control group were identified. These genes from the hippocampus included neurotrophic factors, and genes related to Alzheimer disease and neuronal guidance. It is also noted that genes showing significant changes are greatly different between the whole brain and hippocampus.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Fujioka, T.: "Materno-fetal coordination of stress-induced Fos expression in the hypothalamic praventricular nucleus during pregnancy"Neuroscience. 118. 409-415 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Lu, Y.: "Effects of repeated stress on regeneration of serotonergic and noradrenergic axons in the cerebral cortex of adult rats"Neuroscience Letters. 339・3. 227-230 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iqbal Chowdhury, G.M.: "Cortical spreading depression affects Fos expression in the hypothalamic paraventricular nucleus and the cerebral cortex of both hemispheres"Neuroscience Research. 45. 149-155 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakata, Y.: "Paradoxical rise in brainstem PO2 following umbilical cord occlusion in full-term rat fetuses"Neuroscience Letters. 330. 167-170 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishikawa, A.: "Neurons in the lateral paragigantocellular nucleus projecting to the infralimbic cortex in rats : electrical activity and response to changes in blood pressure"Neuroscience Letters. 311. 57-60 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hashimoto, M.: "Modulating effects of prenatal stress on hyperthermia induced in adult rat offspring by restraint or LPS-induced stress"Physiology & Behavior. 73. 125-132 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishiike, S.: "Effect of AF644, a cholinergic neurotoxin, on footshock stimulation induced locus coeruleus excitation in rats"Neuroscience Letters. 302. 33-36 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujioka, T.: "Mild prenatal stress enhances learning performance in the non-adopted rat offspring"Neuroscience. 103. 301-307 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Fujioka: "Materno-fetal coordination of stress-induced Fos expression in the hypothalamic praventricular nucleus during pregnancy"Neuroscience. 118. 409-415 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] G.M, Iqbal Chowdhury: "Cortical spreading depression affects Fos expression in the hypothalamic paraventricular nucleus and the cerebral cortex of both hemispheres"Neurosci.Res.. 45. 149-155 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Liu: "Effects of repeated stress on regeneration of serotonergic and noradrenergic axons in the cerebral cortex of adult rats"Neurosci.Lett.. 339・3. 227-230 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Sakata: "Paradoxical rise in brainstem P02 following umbilical cord occlusion in full-term rat fetuses"Neurosci.Lett.. 330. 167-170 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Ishikawa: "Neurons in the lateral paragigantocellular nucleus projecting to the infralimbic cortex in rats : electrical activity and response to changes in blood pressure"Neurosci.Lett.. 311. 57-60 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Hashimoto: "Modulating effects of prenatal stress on hyperthermia induced in adult rat offspring by restraint or LPS-induced stress"Physiol. & Behav.. 73. 125-132 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Nishiike: "Effect of AF644, a cholinerglc neurotoxin, on footshock stimulation induced locus coeruleus excitation in rats"Neurosci.Lett.. 302. 33-36 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Fujioka: "Mild prenatal stress enhances learning performance in the non-adopted rat offspring"Neuroscience. 103. 301-307 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujioka, T.: "Materno-fetal coordination of stress-induced Fos expression in the hypothalamic praventricular nucleus during pregnancy"Neuroscience. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iqbal Chowdhury, G.M.: "Cortical spreading depression affects Fos expression in the hypothalamic paraventricular nucleus and the cerebral cortex of both hemispheres"Neuroscience Research. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Liu, Y.: "Effects of repeated stress on regeneration of serotonergic and noradrenergic axons in the cerebral cortex of adult rats"Neuroscience Letters. 339・3. 227-230 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakata, Y.: "Paradoxical rise in brainstem PO2 following umbilical cord occlusion in full-term rat fetuses"Neuroscience Letters. 330. 167-170 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishikawa, A.: "Neurons in the lateral paragigantocellu ; ar nucleus projecting to the infralimbic cortex in rats : electrical activity and response to change in bloodpressure."Neuroscience Letters. 311. 57-60 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hashimoto, M.: "Modulating effects of prenatal stress on hyperthermia induced in adult rat offspring by restraint or LPS-induced stress."Physiology & Behavior. 73. 125-132 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nishiike, S.: "Effect of AF64A, a cholinergic neurotoxin, on footshock stimulation induced locus coeruleus excitation in rats."Neuroscience Letters. 302. 33-36 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujioka, T.: "Mild prenatal stress enhances learning performance in the non-adopted rat offspring."Neuroscience. 103. 301-307 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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