2002 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) 谷浦秀夫金沢大学, 自然科学研究科, 助教授 (80263325) 中村洋一大阪府立大学, 大学院・農学生命科学研究所, 教授 (90180413)
Keywords	グルタミン酸シグナル / ストレス負荷 / トラウマ / 遺伝子転写制御因子 / activator protein-1 / CREB / NMDAレセプター / 可塑性
Research Abstract	過度に強烈なストレス刺激を受けると、一過性の短時間負荷の場合でも、心的外傷後ストレス障害(トラウマ)が発生する。これは一過性のストレス負荷の影響が、脳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、以前に実験動物に拘束水浸ストレスを負荷すると、視床下部と小脳において、可塑性形成プロセスに関与するNMDAレセプター結合が著明に上昇する事実を見出した。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activator protein-1(AP1)およびcyclic AMP response element binding protein (CREB)のDNA結合能を測定した。その結果、副腎では両DNA結合ともに3時間までは、負荷時間に依存して負荷直後に測定すると有意に上昇したが、その上昇の度合いはCREBよりもAP1の方がより著明であった。しかしながら、いずれの時間ストレスを負荷しても、脳内各部位および下垂体では有意なAP1およびCREB DNA結合能に、著明な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。以上の結果より、一過性ストレス負荷は、脳内における特定転写制御因子AP1のDNA結合には、著明な影響を与えないと推察される。

Research Products
(23 results)

All Other

All Publications (23 results)

[Publications] Noritaka Namamichi: "Dual mechanisms of Ca^<2+> increases elicited by N-methyl-D-aspartate in immature and mature cultured cortical neurons"J.Neurosci.Res.. 67. 275-283 (2002)
[Publications] Akiko Takamoto: "Differences between D-and L-aspaftate binding to the Na^+-dependent binding sites on glutamate transporters in frozen sections of rat brain"Life Sci.. 70. 991-1001 (2002)
[Publications] Noritaka Namamichi: "Nuclear degradation of particular Fos family members expressed expressed following injections of NMDA and kainate in murine hippocampus"Neurochem.Res.. 27. 131-138 (2002)
[Publications] Takao Hirai: "Potentiation of nuclear activator protein-1 DNA binding following brief exposure to N-methyl-D-aspartate in immature cultured rat hippocampal neurons"J.Neurosci.Res.. 67. 523-532 (2002)
[Publications] Takao Hirai: "Activator protein-1 complex expressed by magnetism in cultured rat hippocampal neurons"Biochem.Biophys.Res.Comm.. 292. 200-207 (2002)
[Publications] Eiichi Hinoi: "Constitutive expression of heterologous N-methyl-D-aspartate receptor subunits in rat adrenal medulla"J.Neutosci.Res.. 68. 36-45 (2002)
[Publications] Kiyokazu Ogita: "Expression of activator protein-1 complex with DNA binding activity in mitochondria of murine brain following in vivo treatment with kainate"J.Neurosci.. 22. 2561-2570 (2002)
[Publications] Sayumi Fujimori: "Functional GABAB receptors expressed in cultured calvarial osteoblasts"Biochem.Biophys.Res.Comm.. 293. 1445-1452 (2002)
[Publications] Eiichi Hinoi: "Cell death by pyruvate deficiency in proliferative cultured calvarial osteoblasts"Biochem.Biophys.Res.Comm.. 294. 1177-1183 (2002)
[Publications] Eiichi Hinoi: "Demonstration of expression of mRNA for particular AMPA and kainate receptor subunits in immature and mature cultured rat calvarial osteoblasts"Brain Res.. 943. 112-116 (2002)
[Publications] Ken-ichi Ohtani: "In vitro and in vivo antagonistic activities of SM-31900 for the NMDA receptor glycine-binding site"Brain Res.. 944. 165-173 (2002)
[Publications] Eiichi Hinoi: "Facilitation of glutamate release by ionotropic glutamate receptors in osteoblasts"Biochem.Biophys.Res.Commun.. 297. 452-458 (2002)
[Publications] Eiichi Hinoi: "Blocked by N-methyl-D-aspartate of elevation of activator protein-1 binding after stress in rat adrenals"J.Neurosci.Res.. 70. 161-171 (2002)
[Publications] Noritaka Nakamichi: "Blockade by ferrous iron of Ca2+ influx through N-methyl-D-aspartate receptor channels in immature cultured rat cortical neurons"J.Neurochem.. 83. 1-11 (2002)
[Publications] Nobuyuki Kuramoto: "Existence of xenobiotic response element bindling in Dictyostelium"Biohcim.Biophys.Acta. 1578. 1-11 (2002)
[Publications] Tomoya Kitayama: "Possible regulation by N-methyl-D-aspartate receptors of proliferative progenitor cells expressed in adult mouse hippocampal dentate gyrus"J.Neurochem.. 84. 767-780 (2003)
[Publications] Yoichi Nakamura: "Involvement of protein kinase C in glutamate release from cultured microglia"Brain Res.. 962. 122-128 (2003)
[Publications] Koji Murakami: "Potentiation by ATP of lipopolysaccharide-stimulated nitric oxide production in cultured astrocytes"Nuroscience. 117. 37-42 (2003)
[Publications] Nobuyuki Kuramoto: "Modulation of DNA binding of nuclear transcription factors with leucine-zipper motifs by particular endogenous polyamines in murine central and peripheral tissues"Brain Res.. (in press). (2003)
[Publications] Nobuyuki Kuramoto: "Xenobiotic response element binding enriched in both nuclear and microsomal fractions of rat cerebellum"J.Neurochem.. (in press). (2003)
[Publications] Nobuyuki Kuramoto: "Xenobiotic response element binding protein expressed in rat brain"Recent Dev.Biophys.Biochem.. (in press). (2003)
[Publications] Masanori Yoneyama: "Immersion fixation with Carnoy solution for conventional immunohistochemical detection of particular N-methyl-D-aspartate receptor subunits in murine hippocampus"J.Neurosci.Res.. (in press). (2003)
[Publications] Kiyokazu Ogita: "In vivo neuroprotective role of NMDA receptors against kainate-induced excitotoxicity in murine hippocampal pyramidal neurons"J.Neurochem.. (in press). (2003)

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

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

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

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

[Publications] Takao Hirai: "Activator protein-1 complex expressed by magnetism in cultured rat hippocampal neurons"Biochem.Biophys.Res.Comm.. 292. 200-207 (2002)

[Publications] Eiichi Hinoi: "Constitutive expression of heterologous N-methyl-D-aspartate receptor subunits in rat adrenal medulla"J.Neutosci.Res.. 68. 36-45 (2002)

[Publications] Kiyokazu Ogita: "Expression of activator protein-1 complex with DNA binding activity in mitochondria of murine brain following in vivo treatment with kainate"J.Neurosci.. 22. 2561-2570 (2002)

[Publications] Sayumi Fujimori: "Functional GABAB receptors expressed in cultured calvarial osteoblasts"Biochem.Biophys.Res.Comm.. 293. 1445-1452 (2002)

[Publications] Eiichi Hinoi: "Cell death by pyruvate deficiency in proliferative cultured calvarial osteoblasts"Biochem.Biophys.Res.Comm.. 294. 1177-1183 (2002)

[Publications] Eiichi Hinoi: "Demonstration of expression of mRNA for particular AMPA and kainate receptor subunits in immature and mature cultured rat calvarial osteoblasts"Brain Res.. 943. 112-116 (2002)

[Publications] Ken-ichi Ohtani: "In vitro and in vivo antagonistic activities of SM-31900 for the NMDA receptor glycine-binding site"Brain Res.. 944. 165-173 (2002)

[Publications] Eiichi Hinoi: "Facilitation of glutamate release by ionotropic glutamate receptors in osteoblasts"Biochem.Biophys.Res.Commun.. 297. 452-458 (2002)

[Publications] Eiichi Hinoi: "Blocked by N-methyl-D-aspartate of elevation of activator protein-1 binding after stress in rat adrenals"J.Neurosci.Res.. 70. 161-171 (2002)

[Publications] Noritaka Nakamichi: "Blockade by ferrous iron of Ca2+ influx through N-methyl-D-aspartate receptor channels in immature cultured rat cortical neurons"J.Neurochem.. 83. 1-11 (2002)

[Publications] Nobuyuki Kuramoto: "Existence of xenobiotic response element bindling in Dictyostelium"Biohcim.Biophys.Acta. 1578. 1-11 (2002)

[Publications] Tomoya Kitayama: "Possible regulation by N-methyl-D-aspartate receptors of proliferative progenitor cells expressed in adult mouse hippocampal dentate gyrus"J.Neurochem.. 84. 767-780 (2003)

[Publications] Yoichi Nakamura: "Involvement of protein kinase C in glutamate release from cultured microglia"Brain Res.. 962. 122-128 (2003)

[Publications] Koji Murakami: "Potentiation by ATP of lipopolysaccharide-stimulated nitric oxide production in cultured astrocytes"Nuroscience. 117. 37-42 (2003)

[Publications] Nobuyuki Kuramoto: "Modulation of DNA binding of nuclear transcription factors with leucine-zipper motifs by particular endogenous polyamines in murine central and peripheral tissues"Brain Res.. (in press). (2003)

[Publications] Nobuyuki Kuramoto: "Xenobiotic response element binding enriched in both nuclear and microsomal fractions of rat cerebellum"J.Neurochem.. (in press). (2003)

[Publications] Nobuyuki Kuramoto: "Xenobiotic response element binding protein expressed in rat brain"Recent Dev.Biophys.Biochem.. (in press). (2003)

[Publications] Masanori Yoneyama: "Immersion fixation with Carnoy solution for conventional immunohistochemical detection of particular N-methyl-D-aspartate receptor subunits in murine hippocampus"J.Neurosci.Res.. (in press). (2003)

[Publications] Kiyokazu Ogita: "In vivo neuroprotective role of NMDA receptors against kainate-induced excitotoxicity in murine hippocampal pyramidal neurons"J.Neurochem.. (in press). (2003)

米田幸雄金沢大学, 自然科学研究科, 教授 (50094454)