Molecular analyses of neuron-astrocyte-microglia network

我们主要通过分析小胶质细胞的功能来研究神经元与神经胶质细胞之间的相互作用。1)神经保护药物Pepa对小胶质细胞的影响。小胶质细胞在神经退行性疾病和艾滋病痴呆中起重要作用。另一方面，Pepa被报道通过调节神经元上的Flop类型的AMPA受体来增强谷氨酸诱导的电流，并对大鼠脑缺血功能障碍有改善作用。由于小胶质细胞具有AMPA受体(Noda et al.，2000)，我们研究了Pepa对小胶质细胞的影响。结果，Pepa增强了AMPA受体对大鼠脑内分离的小胶质细胞的反应。相反，这些作用的结果是，Pepa抑制了谷氨酸诱导的小胶质细胞释放肿瘤坏死因子-α。这些结果表明，肿瘤坏死因子-α的释放具有神经毒性，因此小胶质细胞对肿瘤坏死因子-α的抑制可能与…有关。更多地保护神经元2)神经元-星形胶质细胞-小胶质细胞之间的网络通过缓激肽受体。缓激肽是一种内源性多肽，会引起疼痛和炎症。通过用缓激肽处理小胶质细胞23小时，我们发现小胶质细胞表达缓激肽受体，并且其表达模式在小胶质细胞激活前后发生了变化。我们现在正在研究小胶质细胞释放哪种细胞因子，并发现至少释放了一氧化氮。这一结果表明，脑内不仅存在小胶质细胞与神经元、星形胶质细胞之间的相互作用，而且小胶质细胞与微血管之间也存在相互作用。这些发现将有助于创造治疗脑损伤的新药物。尽管它被认为是一种新的胶质受体，并被证明是神经元受体，但我们研究了一种新的5-羟色胺受体亚型(5-羟色胺受体亚型)的信号级联，其突变可能与心理障碍有关。3)5-羟色胺受体的多个信号转导。我们发现，与其他5-羟色胺受体亚型不同，5-羟色胺受体与多个信号转导相偶联。较少

We tried to investigat the interaction between neuron and glia by mainly analyzing the function of microglia which is far behind among the rest of glial cells.1) The effects of PEPA (neuroprotective drug) on microglia. Microglial cells play an important role in neurodegenerative diseases and the dementia in AIDS. On the other hand, PEPA was reported to potentiate glutamate-induced currents by modulating flop-type of AMPA-receptors in neurons and had ameliorating effects in ischaemic dysfunction in rat brain. Since microglial cells have AMPA-receptor (Noda et al., 2000), we investigated the effects of PEPA on microglial cells. As a result, PEPA potentiated the AMPA-receptor-induced response in microglia isolated from rat brain. The consequence of these effects were, on the contrary, that PEPA inhibited glutamate-induced TNF-alpha release from microglia. These results suggest that the release of TNF-alpha is neurotoxic, therefore the inhibition of TNF-alpha from microglia may contribute … More to protect neurons.2) Network between neuron-astrocyte-microglia via bradykinin receptors. Bradykinin is an endogenous peptide which causes pain and inflammation. We found that microglia express bradykinin receptors and their expression pattern changed before and after activation of microglia by treating the cells with bradkinin for 23 hours. We are now investigating which kind of cytokines are released from microglia and has found that at least nitric oxide was released. This result indicate that there are not only interaction between microglia and neuron and astrocyte but also between microglia and microvessels in the brain. These findings will contribute to create new therapeutic drug for brain injury.Though it was believed as a new glial receptor and turned out to be neuronal receptor, we investigated the signal cascade of a new serotonin receptor subtype (5-HT_<5A>) whose mutation may be related to psychological disorder.3) Multiple signal transductions of 5-HT_<5A> receptors. We found that 5-HT_<5A> receptors are coupled to multiple signal transductions unlike other 5-HT receptor subtypes. Less