2000 Fiscal Year Annual Research Report

神経回路網の形成・成熟・老化・病的過程におけるアポトーシス制御分子の役割

Research Project

Project/Area Number	12053242
Research Institution	Kyoto University
Principal Investigator	下濱俊京都大学, 医学研究科, 講師 (60235687)
Keywords	発生 / 神経回路網 / 老化 / アポトーシス / カスペース / Bcl-2 / アルツハイマー病 / 神経終末
Research Abstract	個体の発生過程においてはアポトーシスによって臓器の形態形成、不要構造の除去、細胞数の調整、異常なあるいは有害な細胞の除去などが行なわれることがわかってきたが、脳の形成・成熟・老化の過程でアポトーシス調節分子がどのように制御され、神経回路網の発達・維持に関与しているかは殆どわかっていない。本研究では、神経回路網の形成・成熟・老化および病的過程におけるアポトーシス制御分子の役割について解析した。胎仔から生後2年までのWistarラットを用いた研究で、神経回路網の形成・成熟・老化に伴い、脳内Bcl-2ファミリー及びcaspaseファミリータンパク質の発現がそれぞれ特異的に制御されていること、また、興味あることに、神経回路網が大きく破綻し、高度の痴呆を呈するアルツハイマー病脳では脳の発生・生後発達期のアポトーシスが盛んな神経回路網が形成される時期と同様に、caspase-3,Bak,Bad,Bcl-2などのアポートーシス関連分子の発現を増大させる機構が作動していることが示唆された。また、8週齢のラット脳より核、ミエリン分画、神経終末、ミトコンドリア、ミクロゾーム、可溶性分画の細胞分画を調整した。各分画でのcaspaseの分布を免疫化学的に半定量的に解析すると、caspase-2、caspase-3、caspase-6、caspase-9、Apaf-1などは、神経終末分画にも多く存在しており、シナプス可塑性機構に関与していることが示唆された。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Kume T,Nishikawa.H et al: "P75-mediated neuroprotection by NGF against glutamate cytotoxiclity in cortical cultures"Brain Research. 852. 279-289 (2000)
[Publications] Kageyama T,Oeda T. et al: "Coexistence of expanded CAG repeats in the MJDla and DRPLA genes"Neurology. 54. 265-266 (2000)
[Publications] Yawamoto K,Hashimoto K et al: "An IPs-assisted form of Ca^<2+>-induced Ca^<2+> release in neocortical neurons"Neuroreport. 11. 535-539 (2000)
[Publications] Sawada H,Ibi,M et al: "Neuroprotective mechanism of glial cell line-derived neurotrophic tactor in mesercephalic neurons"Journal of Neurochemistry. 74. 1175-1184 (2000)
[Publications] Honda K,Sawada H et al: "Phosphatidylinositol 3-kinase mediates neuroprotection by estrogen in cultured cortical neurons"Journal of Neuroscience Research. 60. 321-327 (2000)
[Publications] Sawada H,Ibi M et al: "Mechanisms of antiapoptotic effects of estrogen in nigral dopaminergic neurons"FASEB Journal. 14. 1202-1214 (2000)
[Publications] Tanino H,Shimohama S et al: "Increase in phospholipose C-δ_1 protein levels in aluminum-treated rat brains"Biochem Biophys Res Commun. 271. 620-625 (2000)
[Publications] Shimohama S,Tanino H et al: "Activation of NADPH oxidase in Alzheimer's disease brains"Biochem Biophys Res Commun. 273. 5-9 (2000)
[Publications] Urushitani M,Inoeu R et al: "Neuroprotective effect of cyclin GMP against radical-induced toxicity in cultured spinal motor neurons"Journal of Neuro science Research. 61. 443-448 (2000)
[Publications] Kageyama T,Nakamura M et al: "The 4F2hc/CAT1 complex transports L-Dopa across the blood-brain barrier"Brain Research. 879. 115-121 (2000)
[Publications] Imura T,Shimohama S: "Opposing effects of adenosiue on the survival of glial cells exposed to chemical ischemia"Journal of Neuroscience Research. 62. 539-546 (2000)
[Publications] Nakanizo T,Urushitani M et al: "Protection of motor neurons by estradiol"Neuro report. 11. 3493-3497 (2000)
[Publications] Kakimara J.Kitamura Y et al: "Bip/GRP78-induced protection of cytokines and uptake of amyloid-β(1-42) peptide in microglia"Biochem Biophys Res Commun. 281. 6-10 (2001)
[Publications] Kageyama T,Imura T et al: "Distribution of the 4F2 light chain, LAT1, in the mouse brain"Neuroreport. 11. 3663-3666 (2000)
[Publications] Urashitani M,Nakamizo T et al: "NMDA receptor-mediated mitochoudrical Ca^<2+> overload in acute extitotoxic motor neurons death : a distinct mechanism from chronic neurotoxicity after Ca^<2+> influx"Journal of Neuroscience Research. 63. 377-387 (2001)
[Publications] Shimohamas,Kihara T: "Nicotinic receptor-mediated protection against beta amyloid neurotoxicity"Biological Psychiatry. (in press). (2001)
[Publications] Kihara T,Shimohama S et al: "Alpha 7 nicotinic receptor transduces signals to PT3 kinase to block AB-induced neurotoxicity"Journal of Biological Chemistry. (in press). (2001)
[Publications] Honda K,Shimohama S et al: "Nongeneric antiapoptotic signal transduction by estrogen in cultured cortical neurons"Journal of Neuroscience Research. (in press). (2001)

2000 Fiscal Year Annual Research Report

神経回路網の形成・成熟・老化・病的過程におけるアポトーシス制御分子の役割

Principal Investigator

下濱 俊 京都大学, 医学研究科, 講師 (60235687)

Research Products

[Publications] Kume T,Nishikawa.H et al: "P75-mediated neuroprotection by NGF against glutamate cytotoxiclity in cortical cultures"Brain Research. 852. 279-289 (2000)

[Publications] Kageyama T,Oeda T. et al: "Coexistence of expanded CAG repeats in the MJDla and DRPLA genes"Neurology. 54. 265-266 (2000)

[Publications] Yawamoto K,Hashimoto K et al: "An IPs-assisted form of Ca^<2+>-induced Ca^<2+> release in neocortical neurons"Neuroreport. 11. 535-539 (2000)

[Publications] Sawada H,Ibi,M et al: "Neuroprotective mechanism of glial cell line-derived neurotrophic tactor in mesercephalic neurons"Journal of Neurochemistry. 74. 1175-1184 (2000)

[Publications] Honda K,Sawada H et al: "Phosphatidylinositol 3-kinase mediates neuroprotection by estrogen in cultured cortical neurons"Journal of Neuroscience Research. 60. 321-327 (2000)

[Publications] Sawada H,Ibi M et al: "Mechanisms of antiapoptotic effects of estrogen in nigral dopaminergic neurons"FASEB Journal. 14. 1202-1214 (2000)

[Publications] Tanino H,Shimohama S et al: "Increase in phospholipose C-δ_1 protein levels in aluminum-treated rat brains"Biochem Biophys Res Commun. 271. 620-625 (2000)

[Publications] Shimohama S,Tanino H et al: "Activation of NADPH oxidase in Alzheimer's disease brains"Biochem Biophys Res Commun. 273. 5-9 (2000)

[Publications] Urushitani M,Inoeu R et al: "Neuroprotective effect of cyclin GMP against radical-induced toxicity in cultured spinal motor neurons"Journal of Neuro science Research. 61. 443-448 (2000)

[Publications] Kageyama T,Nakamura M et al: "The 4F2hc/CAT1 complex transports L-Dopa across the blood-brain barrier"Brain Research. 879. 115-121 (2000)

[Publications] Imura T,Shimohama S: "Opposing effects of adenosiue on the survival of glial cells exposed to chemical ischemia"Journal of Neuroscience Research. 62. 539-546 (2000)

[Publications] Nakanizo T,Urushitani M et al: "Protection of motor neurons by estradiol"Neuro report. 11. 3493-3497 (2000)

[Publications] Kakimara J.Kitamura Y et al: "Bip/GRP78-induced protection of cytokines and uptake of amyloid-β(1-42) peptide in microglia"Biochem Biophys Res Commun. 281. 6-10 (2001)

[Publications] Kageyama T,Imura T et al: "Distribution of the 4F2 light chain, LAT1, in the mouse brain"Neuroreport. 11. 3663-3666 (2000)

[Publications] Urashitani M,Nakamizo T et al: "NMDA receptor-mediated mitochoudrical Ca^<2+> overload in acute extitotoxic motor neurons death : a distinct mechanism from chronic neurotoxicity after Ca^<2+> influx"Journal of Neuroscience Research. 63. 377-387 (2001)

[Publications] Shimohamas,Kihara T: "Nicotinic receptor-mediated protection against beta amyloid neurotoxicity"Biological Psychiatry. (in press). (2001)

[Publications] Kihara T,Shimohama S et al: "Alpha 7 nicotinic receptor transduces signals to PT3 kinase to block AB-induced neurotoxicity"Journal of Biological Chemistry. (in press). (2001)

[Publications] Honda K,Shimohama S et al: "Nongeneric antiapoptotic signal transduction by estrogen in cultured cortical neurons"Journal of Neuroscience Research. (in press). (2001)

下濱俊京都大学, 医学研究科, 講師 (60235687)