Regulation of glutamatergic signalings by niacrophage/microglia

点击翻译按钮获取中文摘要

To elucidate the influence of macrophage/microglia on glutamatergic synaptic transmission in the brain and bone tissues, we first examined the effects of primary cultured microglia transferred onto the organotypic cortical slice cultures. In these microglia-transferred cortical slice cultures, stimulation of the subcortlcal white matter induced fast excitatory postsynaptic potentials followed by N-merhyl-D-aspartate (NMDA) receptor-mediated plateau-like potentials that were never observed in control slice cultures. A similar potentiation of NMDA receptor-mediated postsynaptic responses was also observed by an application of a microglial-conditioned medium (MCMI 10% v/v) in acute cortical slices. These effects of MCM disappeared after boiling or incubation with proteinase K. After fractionation of MCM by anion-exchange chromatography, the enhancing activity of each fraction was quantitated electrophysiologically. When each fraction was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the fraction 24 which showed the most potent enhancing activity on NMDA receptor-mediated responses contained a relatively strong protein band with a molecular mass of approximately 70 kDa. MCM also enhanced both glutamate-and NMDA-induced inward currents recorded from acutely isolated cortical neurons. It was also noted that glutamate and NMDA induced transient large inward currents during an application of MCMI which were never observed in the control condition. These observations strongly suggest that NMDA receptor-mediated responses were potentiated by both heat-and protease-labile (presumably 70 kD-protelns) molecules released from microglia.