1995 Fiscal Year Annual Research Report

神経細胞死における情報伝達系のクロストーク-発生,分化と老化をめぐる接点

Research Project

Project/Area Number	07457125
Research Category	Grant-in-Aid for General Scientific Research (B)
Research Institution	The Open University of Japan
Principal Investigator	鬼頭昭三放送大学, 教養学部, 教授 (00010140)
Co-Investigator(Kenkyū-buntansha)	仙波純一放送大学, 教養学部, 助教授 (30183429)
Keywords	estrogen / Ca^<2+> / ジヒドロピリジン系Ca拮抗薬 / hepatocyte growth factor / insulin-like growth factor / mRNA / dot blotting / in situ hybridization
Research Abstract	estrogenが、発生・分化と深く関わっており老化に伴う神経細胞死のrescueに関与しているという観点から、当初の本年度研究計画に従って実験を進めた。この実験の基礎となる事実は、我々のこれまでの実験によるラット辺縁系培養神経細胞のsurvival rateをestrogenが低濃度では用量依存的に上昇させるという結果である。ラット辺縁系培養神経細胞にestrogenを加えることにより、細胞内Ca^<2+>濃度の上昇をきたすことを従来の実験結果より確認している。この実験系にジヒドロピリジン系Ca拮抗薬を加えることによりCa^<2+>のshort termの上昇が抑制された。このことから、estrogenが細胞膜にも特異的結合部位を有しL型Ca^<2+>チャンネルを通じてCa^<2+>の神経細胞内流入をきたすものと結論した。一方、estrogenは10^<-5>以上の高濃度では逆に培養神経細胞のsurvival rateを抑制することを我々が認めている。これは細胞内Ca^<2+>の過剰な上昇によるものと推定されるが、この濃度のestrogenによる培養神経細胞のsurvival rateの低下をhepatocyte growth factor(HGF)、insulin-like growth factor(IGF)などの近年脳内においてもtrophic factorとして働くことが注目されているgrowth factorsが用量依存的に抑制した。 estrogenのin vivo投与に伴う脳内におけるHGF、IGF mRNAの発現をdot blotting, in situ hybridizationによって検証した。その結果、カイニン酸投与による神経細胞の傷害に伴うこれらneurotrophic factors mRNAの発現をestrogenが一層増強させることを認めた。成熟ラットではestrogen受容体の脳内での存在は視床下部、辺縁系に限定されているが、カイニン酸を投与することによって、周生期にみられたと同じように脳内に広くestrogen受容体が再び出現することをestrogen受容体に対するモノクロナール抗体を用いて免疫組織化学的に確認した。

Research Products

(11 results)

All Other

All Publications (11 results)

[Publications] Semba, J.: "Differential expression of c-fos mRNA in rat perfrontal cortex, striatum, N. accumbens and lateral septum after typical and atypical antipsychotics: an in situ hybridization study." Neurochemistry International. (in press).
[Publications] 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)
[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, an inhibitor of nitric oxide synthase, increases extracellular GABA in the striatum of the freely moving rat." Neuro Report. 34. 1426-1428 (1995)
[Publications] Semba, J.: "Behavioural and neurochemical efects of OPC-14597, a novel antipsychotic drug, on dopaminergic mechanisms in rat brain." Neuropharmacology. 34. 785-791 (1995)
[Publications] 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)
[Publications] Semba, J.: "Characterization of extracllular amino acids in striatum of freely moving rat using in vivo microdialysis." Japanese Journal of Pharmacology. 64. 229- (1994)
[Publications] Kito, S.: "Effects of nicotine on glucocorticoid toxicity on hippocampal neurons." Neurochemical Research. 19. 888-889 (1994)
[Publications] Kito, S.: "Effects of glucocorticoid on Hippocampal Neurons: in vivo and in vitro studies" Neurochemical Research. 18. 832- (1993)
[Publications] 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)
[Publications] Sakata, H.: "Antiarrhythmic drugs, clofilium and cibenzoline are potent inhibitors of glibenclamide-sensitive K_+ currents in Xenopus oocytes." Br. J. Pharmacol.109. 866-872 (1993)

1995 Fiscal Year Annual Research Report

神経細胞死における情報伝達系のクロストーク-発生,分化と老化をめぐる接点

Principal Investigator

鬼頭 昭三 放送大学, 教養学部, 教授 (00010140)

Research Products

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

[Publications] 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)

[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, an inhibitor of nitric oxide synthase, increases extracellular GABA in the striatum of the freely moving rat." Neuro Report. 34. 1426-1428 (1995)

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

[Publications] 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)

[Publications] Semba, J.: "Characterization of extracllular amino acids in striatum of freely moving rat using in vivo microdialysis." Japanese Journal of Pharmacology. 64. 229- (1994)

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

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

[Publications] 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)

[Publications] Sakata, H.: "Antiarrhythmic drugs, clofilium and cibenzoline are potent inhibitors of glibenclamide-sensitive K_+ currents in Xenopus oocytes." Br. J. Pharmacol.109. 866-872 (1993)

鬼頭昭三放送大学, 教養学部, 教授 (00010140)