1996 Fiscal Year Annual Research Report

Estrogenと神経細胞死 -その分子生物学的メカニズム-

Research Project

Project/Area Number	07044291
Research Institution	University of the Air
Principal Investigator	鬼頭昭三放送大学, 教養学部, 教授 (00010140)
Co-Investigator(Kenkyū-buntansha)	MAGGI A. Ins. of Pharmacolgy Sci., Univ. of Milan, Associate BARNARD E. A Royal Free Hosp. Sch. of Medicine, Professor JOH Tong H Cornell University Medical College, Professor 三好理絵 Royal Free Hosp. Sch. of Medicine, Research A (80209965) 仙波純一放送大学, 教養学部, 助教授 (30183429) 野村靖幸北海道大学, 薬学部, 教授 (00034041) 遠山正彌大阪大学, 医学部, 教授 (40028593) OLSEN Richar UCLA School of Medicine, Professor
Keywords	Estrogen / Hepatocyte growth factor / Insulin-like growth factor / Gel shift assay / 神経栄養因子 / カイニン酸 / 神経可塑性 / AP-1結合活性
Research Abstract	1.前年度にカイニン酸を投与して神経細胞に傷害を与えたラットに、あらかじめestrogenを投与すると、ラット大脳の広い領域にわたって著明なestrogen受容体の周生期にみられたと同じような再出現、および辺縁系におけるその増加を認めているが、この点をさらに免疫組織化学的に確認するとともに、in situ hybridizationによってもestrogen受容体mRNAの再出現及び増加が見られることを確認した。ことに、海馬CA3領域におて著明であった。 2.前年度にカイニン酸全身投与に先立ってestrogenを投与することにより、HGF、IGFIおよびIIなどの神経栄養因子mRNA発現の上昇が見られることを認めたが、今年度は、IGFIに限定して研究を進めることにした。その第1段階として、estrogen単独投与によるAP-1結合活性の時間的推移をgel shift assayによって観察した。estrogen投与後、30〜120分にかけてAP-1結合活性の持続的上昇が見られることを認めた。 3.カイニン酸全身投与に先立ってestrogenを投与することにより、IGFImRNAの上昇が見られることをdot blot分析法で既に認めているが、この点をさらにin situ hybridizationによって確認するとともに免疫組織化学染色によってIGFそのものの上昇が起こることを認めた。 4.カイニン酸全身投与に先立ってestrogenを投与することにより、ラット海馬を中心としてGAP43の出現が見られることを免疫組織化学的に観察した。 5.以上の結果から、estrogenがカイニン酸による神経細胞死に対してestrogen受容体の増加、AP-1結合活性の上昇、IGFIの誘導、GAP43の出現という経路をとって、神経修復に関与している可能性があるものと考えた。

Research Products

(22 results)

All Other

All Publications (22 results)

[Publications] 新郷明子: "ゲルシフトアッセイからみたエストロゲンとニコチンのクロストーク" 医学と生物学. 134/1. 3-7 (1997)
[Publications] Semba, J.: "Nlcotine protects against the dexamrthasone potentlatlon of kainic acid-induced neurotoxicity in cultured hippocampal neurons." Brain Research. 735. 335-338 (1996)
[Publications] Semba, J.: "Differentlal expression of c-fos mRNA in rat prefrontal cortex, striutum, N. accumbens and lateral septum after typical and atypical antipsychotics : an in situ hybridization study." Neurochemistry International. 29/4. 435-442 (1996)
[Publications] 新郷明子: "カイニン酸傷害脳に対するestrogenの影響" 神経化学. 35/6. 510-511 (1996)
[Publications] 新郷明子: "エストロゲンと脳可塑性に関する研究" 医学と生物学. 133/5. 189-193 (1996)
[Publications] 新郷明子: "カイニン酸とAP-1 DNA結合活性-その時間的推移-" 医学と生物学. 133/5. 195-199 (1996)
[Publications] Semba, J.: "Characterization of extracellular amino acids in strlatum of freely moving rats by in vivo microdialysis." Journal of Neural Transmission. 100. 39-52 (1996)
[Publications] Semba, J.: "Differential expression of c-fos mRNA in rat striatum, N. accumbens and prefrontal cortex after haloperidol, suipiride and clozapine : an in situ hybridization study." Japanese Journal of Pharmacology. 67. 143 (1995)
[Publications] Kito, S.: "Effects of estrogen on cultured limbic neurons." Japanese Journal of Pharmacology. 67. 157 (1995)
[Publications] Semba, J.: "N^G-monomethyl-_L-arginine, ainhibitor of nitric oxide synthase, Increases extracellular GABA in the striatum of the freely moving rat." Neuro Report. 6. 1426-8 (1995)
[Publications] Semba, J.: "Behavioural and neurochemical effect of OPC-14597, a novel antipsychotic drug, on dopaminergic mechanisms in rat brain." Neuropharmacology. 34. 785-91 (1995)
[Publications] Semba, J.: "Effect of systemic dexamethasone on extracellular amino acids (glutamate, aspartate, glycine and GABA) and acetylcholine release in rat hippocampus in vivo microdialysis." Functional Neurology. 10. 17-21 (1995)
[Publications] Gordey, M.: "Zine modulation of GABBA receptor-mediated chloride flux in rat hippocampal slices." Brain Res.691/1-2. 125-32 (1995)
[Publications] Tsuda, M.: "Induction of SPI-3 mRNA, encoding a serine protease inhibitor, in gerbil hippocampus after trainsient forebrain ischemia." Brain Res. Mol. Brain Res.35/1-2. 314-318 (1996)
[Publications] Taguchi, A.: "Molecular cloning of novel leucine-rich repeat proteins and their expression in the developing mouse nervous system." Brain Res. Mol. Brain Res.35/1-2. 31-40 (1996)
[Publications] Oda, H.: "G (o) protein does not regulate ATP-stimulated [Ca^<2+>] i elevation or noradrenaline release in PC12 cells." Arch. Biochem. Biophys.332/1. 1-7 (1996)
[Publications] Itano, Y.: "Regulation of Bcl-2 protein expression in human neuroblastoma SH-SY5Y cells : positive and negative effects of protein kinases C and A, respectively." J. of Neurochem.67/1. 131-137 (1996)
[Publications] Conti, B.: "Inducible cAMP early repressor can modulate tyrosine hydroxylase gene expression after stimulation of cAMP synthesis." J. of Biol. Chem.271. 25375-81 (1996)
[Publications] Jahng. J. W.: "Alternate promoters in the rat aromatic L-amino acid decarboxylase gene for neuronal and nonneuronal expression : an in situ hybridization study." J. of Neurochem.66. 14-19 (1996)
[Publications] Webb, T. E.: "A novel G protein-coupled P2 purinoceptor (P2Y3) activated preferentially bu nucleoside diphosphates." Mol. Pharmacol.50/2. 258-65 (1996)
[Publications] Patrone, C.: "Cross-coupling between insulin and estrogen receptor in human neuroblastoma cells." Mol. Endocrinol.10/5. 499-507 (1996)
[Publications] Carlo, P.: "Monoamine oxidase B expression is selectively regulated by dexamethasone in cultured rat astrocytes." Brain Research. 711/1-2. 175-83 (1996)

1996 Fiscal Year Annual Research Report

Estrogenと神経細胞死 -その分子生物学的メカニズム-

Principal Investigator

鬼頭 昭三 放送大学, 教養学部, 教授 (00010140)

Research Products

[Publications] 新郷 明子: "ゲルシフトアッセイからみたエストロゲンとニコチンのクロストーク" 医学と生物学. 134/1. 3-7 (1997)

[Publications] Semba, J.: "Nlcotine protects against the dexamrthasone potentlatlon of kainic acid-induced neurotoxicity in cultured hippocampal neurons." Brain Research. 735. 335-338 (1996)

[Publications] Semba, J.: "Differentlal expression of c-fos mRNA in rat prefrontal cortex, striutum, N. accumbens and lateral septum after typical and atypical antipsychotics : an in situ hybridization study." Neurochemistry International. 29/4. 435-442 (1996)

[Publications] 新郷 明子: "カイニン酸傷害脳に対するestrogenの影響" 神経化学. 35/6. 510-511 (1996)

[Publications] 新郷 明子: "エストロゲンと脳可塑性に関する研究" 医学と生物学. 133/5. 189-193 (1996)

[Publications] 新郷 明子: "カイニン酸とAP-1 DNA結合活性-その時間的推移-" 医学と生物学. 133/5. 195-199 (1996)

[Publications] Semba, J.: "Characterization of extracellular amino acids in strlatum of freely moving rats by in vivo microdialysis." Journal of Neural Transmission. 100. 39-52 (1996)

[Publications] Semba, J.: "Differential expression of c-fos mRNA in rat striatum, N. accumbens and prefrontal cortex after haloperidol, suipiride and clozapine : an in situ hybridization study." Japanese Journal of Pharmacology. 67. 143 (1995)

[Publications] Kito, S.: "Effects of estrogen on cultured limbic neurons." Japanese Journal of Pharmacology. 67. 157 (1995)

[Publications] Semba, J.: "N^G-monomethyl-_L-arginine, ainhibitor of nitric oxide synthase, Increases extracellular GABA in the striatum of the freely moving rat." Neuro Report. 6. 1426-8 (1995)

[Publications] Semba, J.: "Behavioural and neurochemical effect of OPC-14597, a novel antipsychotic drug, on dopaminergic mechanisms in rat brain." Neuropharmacology. 34. 785-91 (1995)

[Publications] Semba, J.: "Effect of systemic dexamethasone on extracellular amino acids (glutamate, aspartate, glycine and GABA) and acetylcholine release in rat hippocampus in vivo microdialysis." Functional Neurology. 10. 17-21 (1995)

[Publications] Gordey, M.: "Zine modulation of GABBA receptor-mediated chloride flux in rat hippocampal slices." Brain Res.691/1-2. 125-32 (1995)

[Publications] Tsuda, M.: "Induction of SPI-3 mRNA, encoding a serine protease inhibitor, in gerbil hippocampus after trainsient forebrain ischemia." Brain Res. Mol. Brain Res.35/1-2. 314-318 (1996)

[Publications] Taguchi, A.: "Molecular cloning of novel leucine-rich repeat proteins and their expression in the developing mouse nervous system." Brain Res. Mol. Brain Res.35/1-2. 31-40 (1996)

[Publications] Oda, H.: "G (o) protein does not regulate ATP-stimulated [Ca^<2+>] i elevation or noradrenaline release in PC12 cells." Arch. Biochem. Biophys.332/1. 1-7 (1996)

[Publications] Itano, Y.: "Regulation of Bcl-2 protein expression in human neuroblastoma SH-SY5Y cells : positive and negative effects of protein kinases C and A, respectively." J. of Neurochem.67/1. 131-137 (1996)

[Publications] Conti, B.: "Inducible cAMP early repressor can modulate tyrosine hydroxylase gene expression after stimulation of cAMP synthesis." J. of Biol. Chem.271. 25375-81 (1996)

[Publications] Jahng. J. W.: "Alternate promoters in the rat aromatic L-amino acid decarboxylase gene for neuronal and nonneuronal expression : an in situ hybridization study." J. of Neurochem.66. 14-19 (1996)

[Publications] Webb, T. E.: "A novel G protein-coupled P2 purinoceptor (P2Y3) activated preferentially bu nucleoside diphosphates." Mol. Pharmacol.50/2. 258-65 (1996)

[Publications] Patrone, C.: "Cross-coupling between insulin and estrogen receptor in human neuroblastoma cells." Mol. Endocrinol.10/5. 499-507 (1996)

[Publications] Carlo, P.: "Monoamine oxidase B expression is selectively regulated by dexamethasone in cultured rat astrocytes." Brain Research. 711/1-2. 175-83 (1996)

鬼頭昭三放送大学, 教養学部, 教授 (00010140)

[Publications] 新郷明子: "ゲルシフトアッセイからみたエストロゲンとニコチンのクロストーク" 医学と生物学. 134/1. 3-7 (1997)

[Publications] 新郷明子: "カイニン酸傷害脳に対するestrogenの影響" 神経化学. 35/6. 510-511 (1996)

[Publications] 新郷明子: "エストロゲンと脳可塑性に関する研究" 医学と生物学. 133/5. 189-193 (1996)

[Publications] 新郷明子: "カイニン酸とAP-1 DNA結合活性-その時間的推移-" 医学と生物学. 133/5. 195-199 (1996)