MECHANISM OF NEURONAL DEATH AND REGENERATION

神经元死亡和再生的机制

• 批准号: 10470038
• 负责人: SHIMIZU Takao
• 金额: $ 9.54万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470038/
• 关键词: Neuron; Glial cells; Lipid mediators; Platelet-activating factor; Leukotrienes; ホスホリバーゼA2; リゾホスファチジン酸; ホスホリパーゼA_z; アラキドレ酸; ニューロン; ミクログリア

Neuronal survival and death are determined by multiple factors including neuronal activity as well as an influence from surrounding glia. In this project, we focus on various lipid mediators in terms of its ability of interaction between neuron and glia. We found that various lipid mediators are produced by stimuli, and play roles in the network as follows. LPA, produced by various cells, stimulates growth and cell maturation of neuron as well as proliferation of astrocytes. LPA also releases various cytokines and neurotrophis (NGF, BDNF) from astroglia, which activates neuronal cells. PAP is released from neuron by the NMDA stimulation, and acts on microglia. Microglia produces NO, and causes chemotaxis towards neuron, suggesting the role of microglia for repairing neuronal cells. PAF receptor-deficient mice and phospholipase A2 (cPLA2)-deficient mice are established, and their congenic mice are now available by backcrossing. The exact roles of these lipid mediators will be clarified by extensive analyses of their phenotypes.

神经元的存活和死亡由多种因素决定，包括神经元活动以及周围神经胶质细胞的影响。在这个项目中，我们重点关注各种脂质介质在神经元和神经胶质细胞之间相互作用的能力。我们发现各种脂质介质是由刺激产生的，并在网络中发挥如下作用。 LPA 由多种细胞产生，刺激神经元的生长和细胞成熟以及星形胶质细胞的增殖。 LPA 还从星形胶质细胞中释放各种细胞因子和神经营养物质（NGF、BDNF），从而激活神经元细胞。 PAP 通过 NMDA 刺激从神经元中释放出来，作用于小胶质细胞。小胶质细胞产生 NO，并引起对神经元的趋化性，表明小胶质细胞在修复神经元细胞中的作用。建立了 PAF 受体缺陷型小鼠和磷脂酶 A2 (cPLA2) 缺陷型小鼠，并且现在可以通过回交获得它们的同源小鼠。这些脂质介质的确切作用将通过对其表型的广泛分析来阐明。

项目成果

Aihara.M.el al.: "Interaction between neuron and microgliamedated by platelet-activating factor"Genes to Cells. (in press). (2000)

Aihara.M.el al.：“神经元和小胶质细胞之间的相互作用由血小板激活因子”基因到细胞。

Tabuchi, S. et al.: "Lysophosphatidic acid stimulates neurotrophin production in astrocytes"Neurochem. Res.. (in press). (2000)

Tabuchi, S. 等人：“溶血磷脂酸刺激星形胶质细胞中神经营养素的产生”Neurochem。

Ishii, S.et al.: "Impaired anaphylactic responses with intact sensitivity to endotoxin in mice lacking a PAF receptor" J.Exp.Med.187・11. 1779-1788 (1998)

Ishii, S.et al.：“缺乏 PAF 受体的小鼠对内毒素的敏感性受损”J.Exp.Med.187·11（1998）。

Ishii, I et al.: "Agonist-induced sequestration, veulcling and resensi-tization of platelit-activating factor receptor" J.Biol.Chem.273・16. 9878-9885 (1998)

Ishii，I 等人：“激动剂诱导的血小板激活因子受体的隔离、释放和再敏化”J.Biol.Chem.273·16 (1998)。

Airaha, M. et al.: "Interaction between neuron and glia mediated by platelet-activating factor."Genes to Cells. (in press). (2000)

Airaha, M. 等人：“血小板激活因子介导的神经元和神经胶质细胞之间的相互作用。”基因到细胞。