1995 年度実績報告書

Estrogenと神経細胞死-その分子生物学的メカニズム-

研究課題

研究課題/領域番号	07044291
研究機関	放送大学
研究代表者	鬼頭昭三放送大学, 教養学部, 教授 (00010140)
研究分担者	MAGGI A. Ins. of Pharmacology Science University o, Associate 三好理絵 Royal Free Hospital School of Medicin, Research A (80209965) 仙波純一放送大学, 教養学部, 助教授 (30183429) BARNARD Elic Royal Free Hospital School of Medicine, Professor JOH Tong H. Cornell University Medical College, Professor 遠山正彌大阪大学, 医学部, 教授 (40028593) OLSEN Richar UCLA School of Medicine, Professor
キーワード	Estrogen / Hepatocyte growth factor / Insulin-like growth factor / LDH effluxmetry / 神経細胞栄養因子 / カイニン酸 / 神経可塑性 / Estrogen受容体
研究概要	1.estrogenが10^<-6>〜10^<-9>の範囲内ではneuronに対してprotectiveに働き、10^<-5>以上の濃度ではneurotoxicに働く我々の実験結果をふまえ、estrogenのneuroprotectiveな作用のメカニズムを探るための実験が行われた。hepatocyte growth factor(HGF)と並んでinsulin-like growth factorがこのメカニズムと関わっている可能性があり、従来から行ってきたLDH effluxmetryの手法を用いてIGFのneuron survivalに対する影響を観察した。その結果、IGF I及びII、ともにラット辺縁系培養神経細胞のneuron survival rateを増加させることを認めた。 2.ラットにカイニン酸を全身投与した後、さらにestrogenを投与し、HGF、IGF I及びIIなどの神経細胞栄養因子mRNA発現がestrogenを投与しない場合と比べて、どのように影響されるか観察した。その結果、カイニン酸注射後3日後に観察した限りでは、estrogen投与によってIGF I mRNA発現の著明な上昇、IGF IIの同様な傾向がdot blot法によってみられた。 3.estrogenの神経可塑性機能の発現の前提条件としてラットにカイニン酸を投与し神経細胞に傷害を与えた後、周生期と同じように大脳にestrogen受容体が再び出現するか否かをestrogen受容体に対するmonoclonal抗体を用いて免疫組織化学的に検証した。その結果、ラットの大脳皮質の広い領域にわたって、ことに前頭部に著明にカイニン酸による神経細胞の傷害に引き続いてestrogen受容体が発現することを認めた。

研究成果
(16件)

すべてその他

すべて文献書誌 (16件)

[文献書誌] Semba,J.: "Differential expression of c-fos mRNA in rat prefrontal cortex,striatum,N.accumbens and lateral septum after typical and atypical antipsychotics:an in situ hybridization study." Neurochemistry International. (in press).
[文献書誌] Semba,J.: "Differential expression of c-fos mRNA in rat striatum,N.accumbens and prefrontal cortex after haloperidol,sulpiride and clozapine:an in situ hybridization study." Japanese Journal of Pharmacology. 67. 143 (1995)
[文献書誌] Kito,S.: "Effects of estrogen on cultured limbic neurons." Japanese Journal of Pharmacology. 67. 157 (1995)
[文献書誌] Semba,J.: "NG-monomethyl-L-arginine,an inhibitor of nitric oxide synthase,increases extracellular GABA in the striatum of the freely moving rat." Neuro Report. 34. 1426-28 (1995)
[文献書誌] Semba,J.: "Behavioural and neurochemical effects of OPC-14597,a novel antipsychotic drug,on dopaminergic mechanisms in rat brain." Neuropharmacology. 34. 785-791 (1995)
[文献書誌] Semba,J.: "Effects 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)
[文献書誌] Olsen,R.W.: "Neuroactive steroid modulation of GABAA receptors." Adv.Biochem.Psychopharmacol.48. 57-74 (1995)
[文献書誌] Mori,T.: "Differential expression of the eph family of receptor tyrosine kinase genes(sek,elk,eck)in the developing neurons system of the mouse." Brain Res.Mol.Brain Res.29. 325-35 (1995)
[文献書誌] Cubells,J.F.: "Differential in vivo regulation of mRNA encoding the norepinephrine transporter and tyrosine hydroxylase in rat adrenal medulla and locus ceruleus." J.Neurochem.65. 502-9 (1995)
[文献書誌] Barnard,E.A.: "The molecular biology of GABAA receptors and their structural determinants." Adv.Biochem.Psychopharmacol.48. 1-16 (1995)
[文献書誌] Magaline,A.: "Specificity of action of a herpes virus VP16/tetracycline-dependent trans-activator in mammalian cell cultures." DNA cell Biol.14. 665-71 (1995)
[文献書誌] Kitamura,Y.: "Suppressive effect of FK-506,a novel immunosuppressant against MPTP-induced dopamine depletion in the striatum of young C57BL/6 mice." J.Neuroimmunol.50. 221-4 (1994)
[文献書誌] Semba,J.: "Characterization of extracellular amino acids in striatum of freely moving rat using in vivo microdialysis." Japanese Journal of Pharmacol.64. 229 (1994)
[文献書誌] Kito,S.: "Effects of nicotine on glucocorticoid toxicity on hippocampal neurons." Neurochemical Research. 19. 888-889 (1994)
[文献書誌] Kito,S.: "Effects of glucocorticoid on Hippocampal Neurons:in vivo and in vitro studies." Neurochemical Research. 18. 832 (1993)
[文献書誌] Semba,J.: "Antiepileptic drug pharmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid milacemide." Br.J.Pharmacol.108. 1117-1124 (1993)

1995 年度 実績報告書

Estrogenと神経細胞死-その分子生物学的メカニズム-

研究代表者

鬼頭 昭三 放送大学, 教養学部, 教授 (00010140)

研究成果

[文献書誌] Semba,J.: "Differential expression of c-fos mRNA in rat prefrontal cortex,striatum,N.accumbens and lateral septum after typical and atypical antipsychotics:an in situ hybridization study." Neurochemistry International. (in press).

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

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

[文献書誌] Semba,J.: "NG-monomethyl-L-arginine,an inhibitor of nitric oxide synthase,increases extracellular GABA in the striatum of the freely moving rat." Neuro Report. 34. 1426-28 (1995)

[文献書誌] Semba,J.: "Behavioural and neurochemical effects of OPC-14597,a novel antipsychotic drug,on dopaminergic mechanisms in rat brain." Neuropharmacology. 34. 785-791 (1995)

[文献書誌] Semba,J.: "Effects 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)

[文献書誌] Olsen,R.W.: "Neuroactive steroid modulation of GABAA receptors." Adv.Biochem.Psychopharmacol.48. 57-74 (1995)

[文献書誌] Mori,T.: "Differential expression of the eph family of receptor tyrosine kinase genes(sek,elk,eck)in the developing neurons system of the mouse." Brain Res.Mol.Brain Res.29. 325-35 (1995)

[文献書誌] Cubells,J.F.: "Differential in vivo regulation of mRNA encoding the norepinephrine transporter and tyrosine hydroxylase in rat adrenal medulla and locus ceruleus." J.Neurochem.65. 502-9 (1995)

[文献書誌] Barnard,E.A.: "The molecular biology of GABAA receptors and their structural determinants." Adv.Biochem.Psychopharmacol.48. 1-16 (1995)

[文献書誌] Magaline,A.: "Specificity of action of a herpes virus VP16/tetracycline-dependent trans-activator in mammalian cell cultures." DNA cell Biol.14. 665-71 (1995)

[文献書誌] Kitamura,Y.: "Suppressive effect of FK-506,a novel immunosuppressant against MPTP-induced dopamine depletion in the striatum of young C57BL/6 mice." J.Neuroimmunol.50. 221-4 (1994)

[文献書誌] Semba,J.: "Characterization of extracellular amino acids in striatum of freely moving rat using in vivo microdialysis." Japanese Journal of Pharmacol.64. 229 (1994)

[文献書誌] Kito,S.: "Effects of nicotine on glucocorticoid toxicity on hippocampal neurons." Neurochemical Research. 19. 888-889 (1994)

[文献書誌] Kito,S.: "Effects of glucocorticoid on Hippocampal Neurons:in vivo and in vitro studies." Neurochemical Research. 18. 832 (1993)

[文献書誌] Semba,J.: "Antiepileptic drug pharmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid milacemide." Br.J.Pharmacol.108. 1117-1124 (1993)

1995 年度実績報告書

鬼頭昭三放送大学, 教養学部, 教授 (00010140)