2003 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)	檜井栄一金沢大学, 薬学部, 助手 (70360865) 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・農学生命科学研究科, 教授 (90180413)
Keywords	グルタミン酸シグナル / ストレス負荷 / トラウマ / 神経系前駆細胞 / BrdU取り込み活性 / 海馬歯状回顆粒細胞 / クラスター形成 / 神経細胞新生
Research Abstract	成熟脳においても脳室下帯や海馬歯状回においては、発達脳の場合と同様に神経系前駆細胞が存在して、ニューロン新生が行われることが明らかとなっている。したがって、成熟マウス海馬歯状回に発現する神経系前駆細胞のストレス負荷に伴う影響について、新規DNA合成の指標となる、5-bromo-2-deoxyuridine(BrdU)の取り込み活性により検討を行った。その目的で、成熟Std-ddY系雄性マウスを金属製のストレスケージにより拘束して、25℃の水浴中に鎖骨下まで各時間浸してストレス負荷を行った。胃粘膜に対するストレス負荷の影響は検鏡により確認した。BrdU(50mg/kg)は、ストレス3時間負荷直後と12時間後に合計2回腹腔内投与した。最初のBrdU投与から24時間後に、4%パラホルムアルデヒド液を用いて動物の灌流固定を行ったのち、厚さ50μmの凍結海馬冠状切片を作成し、BrdU抗体を用いて免疫組織化学法を行った。両側の海馬におけるsubgranular layerおよびhilus内のBrdU陽性細胞数、クラスター形成細胞数、およびクラスター数をそれぞれ計測して定量化した。その結果、動物へのストレス負荷時間の長さに依存して、激しい出血性胃粘膜傷害が認められた。成熟マウス脳海馬歯状回では、顆粒細胞層および側脳室下帯においてそれぞれBrdU陽性細胞が検出されたが、海馬歯状回において観察された陽性細胞数はBrdU投与後時間経過に伴って減少した。動物にストレスを3時間負荷すると、海馬歯状回で検出されたBrdU陽性細胞数、クラスター形成細胞数、およびクラスター数は、いずれも対照群に比べて有意に減少した。以上の結果から、成熟動物へのストレス負荷は、海馬歯状回に発現する神経系前駆細胞の増殖能を抑制する可能性が示唆される。

Research Products

(22 results)

All Other

All Publications (22 results)

[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"Neuroscience. 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 excitable tissues"Brain Res.. 967. 170-180 (2003)
[Publications] Nobuyuki Kuramoto: "Xenobiotic response element binding enriched in both nuclear and microsomal fractions of rat cerebellum"J.Neurochem.. 85. 264-273 (2003)
[Publications] Nobuyuki Kuramoto: "Xenobiotic response element binding protein expressed in rat brain"Recent Res.Dev.Biophys.Biochem.. 3. 599-611 (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.. 73. 416-426 (2003)
[Publications] Kiyokazu Ogita: "In vivo neuroprotective role of NMDA receptors against kainate-induced excitotoxicity in murine hippocampal pyramidal neurons"J.Neurochem.. 85. 1336-1346 (2003)
[Publications] Naoto Hoshi: "AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonists"Nature Neurosci.. 6. 564-571 (2003)
[Publications] Eiichi Hinoi: "Modulation of cellular differentiation by N-methyl-D-aspartate receptors in osteoblasts"FASEB J.. 17. 1532-1534 (2003)
[Publications] Nobuyuki Kuramoto: "A possible novel mechanism underlying temperature-dependent uptake of [^3H]spermidine in nuclear fractions of murine brain"Brain Res.. 981. 78-84 (2003)
[Publications] Katsura Takano: "Microglial cell death induced by a low concentration of polyamines"Neuroscience. 120. 961-967 (2003)
[Publications] Takeshi Takarada: "Uptake of [^3H]L-serine in rat brain synaptosomal fractions"Brain Res.. 983. 36-47 (2003)
[Publications] Kiyokazu Ogita: "Transcription factor activator protein-1 expressed by kainate treatment can bind to the non-coding region of mitochondrial genome in murine hippocampus"J.Neurosci.Res.. 73. 794-802 (2003)
[Publications] Keiji Inoue: "Possible correlation between abilities of a variety of polyamines to increase activator protein-1 DNA binding and to inhibit [^3H]spermidine transport in nuclear fractions of murine brain"Brain Res.. 987. 126-130 (2003)
[Publications] Keiji Inoue: "Fos-B expression is required for polyamine-induced increase in nuclear activator protein-1 DNA binding in discrete structures of murine brain"J.Neurosci.Res.. 74. 199-209 (2003)
[Publications] Masanori Yoneyama: "Immunohistochemical detection by immersion fixation with Carnoy solution of particular non-N-methyl-D-aspartate receptor subunits in murine hippocampus"Neurochem.Int.. 44. 413-422 (2004)
[Publications] Takao Hirai: "Functional alterations in immature cultured rat hippocampal neurons after sustained exposure to static magnetic fields"J.Neurosci.Res.. 75. 230-240 (2004)
[Publications] Kiyokazu Ogita: "Enhanced binding activity of nuclear antioxidant-response element through possible formation of Nrf2/Fos-B complex after in vivo treatment with kainate in murine hippocampus"Neuropharmacology. 46. 580-589 (2004)
[Publications] Takeshi Takarada: "Possible expression of functional glutamate transporters in rat testis"J.Endocrinol.. (in press). (2004)
[Publications] Tomoya Kitayama: "Regulation of neuronal differentiation by N-methyl-D-aspartate receptors expressed in neural progenitor cells isolated from adult mouse hippocampus"J.Neurosci.Res.. (in press). (2004)
[Publications] Takeshi Takarada: "Accumulation of [^3H]glutamate in cultured rat calvarial osteoblasts"Biochem.Pharmacol.. (in press). (2004)

2003 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] 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"Neuroscience. 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 excitable tissues"Brain Res.. 967. 170-180 (2003)

[Publications] Nobuyuki Kuramoto: "Xenobiotic response element binding enriched in both nuclear and microsomal fractions of rat cerebellum"J.Neurochem.. 85. 264-273 (2003)

[Publications] Nobuyuki Kuramoto: "Xenobiotic response element binding protein expressed in rat brain"Recent Res.Dev.Biophys.Biochem.. 3. 599-611 (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.. 73. 416-426 (2003)

[Publications] Kiyokazu Ogita: "In vivo neuroprotective role of NMDA receptors against kainate-induced excitotoxicity in murine hippocampal pyramidal neurons"J.Neurochem.. 85. 1336-1346 (2003)

[Publications] Naoto Hoshi: "AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonists"Nature Neurosci.. 6. 564-571 (2003)

[Publications] Eiichi Hinoi: "Modulation of cellular differentiation by N-methyl-D-aspartate receptors in osteoblasts"FASEB J.. 17. 1532-1534 (2003)

[Publications] Nobuyuki Kuramoto: "A possible novel mechanism underlying temperature-dependent uptake of [^3H]spermidine in nuclear fractions of murine brain"Brain Res.. 981. 78-84 (2003)

[Publications] Katsura Takano: "Microglial cell death induced by a low concentration of polyamines"Neuroscience. 120. 961-967 (2003)

[Publications] Takeshi Takarada: "Uptake of [^3H]L-serine in rat brain synaptosomal fractions"Brain Res.. 983. 36-47 (2003)

[Publications] Kiyokazu Ogita: "Transcription factor activator protein-1 expressed by kainate treatment can bind to the non-coding region of mitochondrial genome in murine hippocampus"J.Neurosci.Res.. 73. 794-802 (2003)

[Publications] Keiji Inoue: "Possible correlation between abilities of a variety of polyamines to increase activator protein-1 DNA binding and to inhibit [^3H]spermidine transport in nuclear fractions of murine brain"Brain Res.. 987. 126-130 (2003)

[Publications] Keiji Inoue: "Fos-B expression is required for polyamine-induced increase in nuclear activator protein-1 DNA binding in discrete structures of murine brain"J.Neurosci.Res.. 74. 199-209 (2003)

[Publications] Masanori Yoneyama: "Immunohistochemical detection by immersion fixation with Carnoy solution of particular non-N-methyl-D-aspartate receptor subunits in murine hippocampus"Neurochem.Int.. 44. 413-422 (2004)

[Publications] Takao Hirai: "Functional alterations in immature cultured rat hippocampal neurons after sustained exposure to static magnetic fields"J.Neurosci.Res.. 75. 230-240 (2004)

[Publications] Kiyokazu Ogita: "Enhanced binding activity of nuclear antioxidant-response element through possible formation of Nrf2/Fos-B complex after in vivo treatment with kainate in murine hippocampus"Neuropharmacology. 46. 580-589 (2004)

[Publications] Takeshi Takarada: "Possible expression of functional glutamate transporters in rat testis"J.Endocrinol.. (in press). (2004)

[Publications] Tomoya Kitayama: "Regulation of neuronal differentiation by N-methyl-D-aspartate receptors expressed in neural progenitor cells isolated from adult mouse hippocampus"J.Neurosci.Res.. (in press). (2004)

[Publications] Takeshi Takarada: "Accumulation of [^3H]glutamate in cultured rat calvarial osteoblasts"Biochem.Pharmacol.. (in press). (2004)

米田幸雄金沢大学, 自然科学研究科, 教授 (50094454)