Microglial α7 nicotinic acetylcholine receptors drive a phospholipase C/IP3 pathway and modulate the cell activation toward a neuroprotective role

摘要: Microglia perform both neuroprotective and neurotoxic functions in the brain, with this depending on their state of activation release mediators. Upon P2X(7) receptor stimulation, for example, microglia small amounts TNF, which protect neurons, whereas LPS causes massive TNF leading to neuroinflammation. Here we report that, rat primary cultured microglia, nicotine enhances receptor-mediated release, whilst suppressing LPS-induced but without affecting mRNA expression via alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs). In elicited a transient increase intracellular Ca(2+) levels, was abolished by specific blockers nAChRs. However, response independent extracellular blocked U73122, an inhibitor phospholipase C (PLC), xestospongin C, blocker IP(3) receptor. Repeated experiments showed that currents were not detected nicotine-stimulated microglia. Moreover, modulation also C. inhibition associated suppression JNK p38 MAP kinase activation, regulate post-transcriptional steps synthesis. contrast, did alter any enhanced receptor-activated conclusion, microglial nAChRs might drive signaling process involving PLC from stores, rather than function as conventional ion channels. This novel nAChR signal may be involved modification towards role inflammatory strengthening protective function.