MECHANISM OF NEURONAL DEATH AND REGENERATION

神经元的存活和死亡是由多种因素决定的，包括神经元的活动以及周围神经胶质的影响。在本项目中，我们将重点研究各种脂质介质在神经元和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），激活神经元细胞。PAP通过NMDA刺激从神经元释放，作用于小胶质细胞。小胶质细胞产生一氧化氮，并对神经元产生趋化作用，提示小胶质细胞具有修复神经元细胞的作用。建立了PAF受体缺陷小鼠和磷脂酶A2 （cPLA2）缺陷小鼠，并通过回交获得了它们的同源小鼠。这些脂质介质的确切作用将通过对其表型的广泛分析来澄清。

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.