2001 Fiscal Year Annual Research Report

心的外傷後ストレス障害(トラウマ)発症の分子機構解明に関する研究

Research Project

Project/Area Number	13470487
Research Institution	Kanazawa University
Principal Investigator	米田幸雄金沢大学, 自然科学研究科, 教授 (50094454)
Co-Investigator(Kenkyū-buntansha)	倉本展行金沢大学, 薬学部, 助手 (60324092) バルツアーヴラディミールジョセフ金沢大学, 薬学部, 助教授 (50324091) 中村洋一金沢大学, 自然科学研究科, 助教授 (90180413)
Keywords	グルタミン酸 / ストレス / 遺伝子転写制御因子 / activator protein-1 / NMDA / 副腎 / 脳下垂体 / 視床下部
Research Abstract	環境ストレスは、様々な長期的機能変化を生じさせるが、これは一過性のストレス負荷の影響が、生体内に長期間固定される可塑性変化の結果だと考えられる。我々は、以前にストレス負荷に伴うNMDAレセプターの誘導、およびNMDAレセプター活性化による細胞核内転写制御因子発現を見出した。今回は、ストレス負荷による生体機能的変化と可塑性変化との関係を明らかにするため、ストレス負荷に伴うロイシンジッパー型転写制御因子発現について検討した。8週齢のWistar系雄性ラットを金属製ストレスゲージにて拘束し、25℃の恒温槽中で1.5-6時間鎖骨下まで浸すことにより、水浸拘束ストレス負荷を行った。ストレス負荷終了一定時間経過後に、脳内各部位、下垂体および副腎を摘出して細胞核抽出液を調製し、ゲルシフトアッセイにより転写制御因子AP1のDNA結合能を測定した。その結果、3時間ストレス負荷直後では、脳内各部位および下垂体ではAP1DNA結合能にいずれも著明な変化は認められなかったのに対して、副腎において対照群の約5倍のAP1結合上昇が認められた。この副腎AP1結合の上昇は、ストレス負荷終了直後で最も大きく、負荷終了後9時間日までは持続したが、24時間目には有意な結合変化は認められなかった。3時間ストレス負荷終了直後の副腎内AP1結合上昇は、NMDAレセプターアンタゴニストであるMK-801前投与では影響を受けなかったが、NMDAを前投与すると有意に抑制された。免疫組織化学的検討を行ったところ、副腎髄質部にNR1、NR2CおよびNR2Dサブユニットタンパク質の発現が認められた。以上の結果より、一過性のストレス負荷の影響が、特定転写制御因子AP1の発現を介して、副腎で長期固定されると推察される。また、この発現メカニズムに少なくとも一部は、副腎髄質内NMDAレセプターが関与する可能性が示唆される。

Research Products

(15 results)

All Other

All Publications (15 results)

[Publications] Hinoi Eiichi: "Characterization with [^3H]quisqualate of group I metabotropic glutamate recepteor subtype in ratcentral and peripheral excitable tissues"Neurochem. Int.. 38. 277-285 (2001)
[Publications] Hinoi Eiichi: "Group III metabotropic glutamate receptors in cultured rat calvarial osteoblasts"Biochem. Biophys. Res. Comm.. 281. 341-346 (2001)
[Publications] Hinoi Eiichi: "Expression of GluR6/7 subunits of kainate receptors in rat adenohypophysis"Neurochem. Int.. 38. 539-547 (2001)
[Publications] Ogita Kiyokazu: "Effects of glutathione depletion by 2-cyclohexen-1-one on excitatory amino acids-induced enhancement of activator protein-1 DNA binding in murine hippocampus"J. Neurochem.. 76. 1905-1915 (2001)
[Publications] Manabe Takayuki: "Diffferential in vitro degradation of particular Fos family members expressed by kainic acid in nuclear and cytosolic fractions of murine brain"J Neurosci. Res.. 64. 34-42 (2001)
[Publications] Manabe Takayuki: "Degradation of c-Fos protein expressed by N-methyl-D-aspartic acid in nuclear fractions of murine hippocampus"Brain Res.. 905. 34-43 (2001)
[Publications] Ogita Kiyokazu: "Decrease in level of APG-2 a member of the heat shock protein 110 family, in murine brain following systemic administration of kainic acid"Neuropharmacol. 41. 285-293 (2001)
[Publications] Balcar Vladimir J.: "Neurochemistry of L-glutamate transport in the CNS : Thirty years of progress"Coll. Czech. Chem. Comm.. 66. 1315-1340 (2001)
[Publications] Nakamichi Noritaka: "Dual mechanisms of Ca^<2+> increase elicited by N-methyl-D-aspartate in immature and mature cultured cortical neurons"J. Neurosci. Res.. 67. 275-283 (2002)
[Publications] Nakamichi Noritaka: "Nuclear degradation of particular Fos family members expressed following injections of NMDA and kainate in murine hippocampus"Neurochem. Res.. 27. 131-138 (2002)
[Publications] Takamoto Akiko: "Differences between D- and L-aspartate binding to the Na^+-dependent binding sites on glutamate transporters in frozen sections of rat brain"Life Sci.. 70. 991-1001 (2002)
[Publications] Hirai Takao: "Potentiation of nuclear activator protein-1 DNA binding flowing brief exposure to N-methyl-D-aspartate in immature cultured rat hippocampal neurons"J. Neurosci. Res.. 67. 523-532 (2002)
[Publications] Ogita Kiyokazu: "Expression of activator protein-1 complex with DNA binding activity in mitochondria of marine brain following in vivo treatment with kainate"J. Neurosci.. (in press). (2002)
[Publications] Hinoi Eiichi: "Constitutive expression of heterologous N-methyl-D-aspartate receptor subunits in rat adrenal medulla"J. Neurosci. Res.. (in press). (2002)
[Publications] Hirai Takao: "Activator protein-1 complex expressed by magnetism in cultured rat hippocampal neurons"Biochem. Biophys. Res. Comm.. (in press). (2002)

2001 Fiscal Year Annual Research Report

心的外傷後ストレス障害(トラウマ)発症の分子機構解明に関する研究

Principal Investigator

米田 幸雄 金沢大学, 自然科学研究科, 教授 (50094454)

Research Products

[Publications] Hinoi Eiichi: "Characterization with [^3H]quisqualate of group I metabotropic glutamate recepteor subtype in ratcentral and peripheral excitable tissues"Neurochem. Int.. 38. 277-285 (2001)

[Publications] Hinoi Eiichi: "Group III metabotropic glutamate receptors in cultured rat calvarial osteoblasts"Biochem. Biophys. Res. Comm.. 281. 341-346 (2001)

[Publications] Hinoi Eiichi: "Expression of GluR6/7 subunits of kainate receptors in rat adenohypophysis"Neurochem. Int.. 38. 539-547 (2001)

[Publications] Ogita Kiyokazu: "Effects of glutathione depletion by 2-cyclohexen-1-one on excitatory amino acids-induced enhancement of activator protein-1 DNA binding in murine hippocampus"J. Neurochem.. 76. 1905-1915 (2001)

[Publications] Manabe Takayuki: "Diffferential in vitro degradation of particular Fos family members expressed by kainic acid in nuclear and cytosolic fractions of murine brain"J Neurosci. Res.. 64. 34-42 (2001)

[Publications] Manabe Takayuki: "Degradation of c-Fos protein expressed by N-methyl-D-aspartic acid in nuclear fractions of murine hippocampus"Brain Res.. 905. 34-43 (2001)

[Publications] Ogita Kiyokazu: "Decrease in level of APG-2 a member of the heat shock protein 110 family, in murine brain following systemic administration of kainic acid"Neuropharmacol. 41. 285-293 (2001)

[Publications] Balcar Vladimir J.: "Neurochemistry of L-glutamate transport in the CNS : Thirty years of progress"Coll. Czech. Chem. Comm.. 66. 1315-1340 (2001)

[Publications] Nakamichi Noritaka: "Dual mechanisms of Ca^<2+> increase elicited by N-methyl-D-aspartate in immature and mature cultured cortical neurons"J. Neurosci. Res.. 67. 275-283 (2002)

[Publications] Nakamichi Noritaka: "Nuclear degradation of particular Fos family members expressed following injections of NMDA and kainate in murine hippocampus"Neurochem. Res.. 27. 131-138 (2002)

[Publications] Takamoto Akiko: "Differences between D- and L-aspartate binding to the Na^+-dependent binding sites on glutamate transporters in frozen sections of rat brain"Life Sci.. 70. 991-1001 (2002)

[Publications] Hirai Takao: "Potentiation of nuclear activator protein-1 DNA binding flowing brief exposure to N-methyl-D-aspartate in immature cultured rat hippocampal neurons"J. Neurosci. Res.. 67. 523-532 (2002)

[Publications] Ogita Kiyokazu: "Expression of activator protein-1 complex with DNA binding activity in mitochondria of marine brain following in vivo treatment with kainate"J. Neurosci.. (in press). (2002)

[Publications] Hinoi Eiichi: "Constitutive expression of heterologous N-methyl-D-aspartate receptor subunits in rat adrenal medulla"J. Neurosci. Res.. (in press). (2002)

[Publications] Hirai Takao: "Activator protein-1 complex expressed by magnetism in cultured rat hippocampal neurons"Biochem. Biophys. Res. Comm.. (in press). (2002)

米田幸雄金沢大学, 自然科学研究科, 教授 (50094454)