Molecular analyses of neuron-astrocyte-microglia network

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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