G-protein coupled receptor 40 (GPR40), which is expressed ubiquitously in the human brain and pancreas, is a member of the large family of seven-transmembrane receptors and can be activated by polyunsaturated fatty acid (PUFA), in particular docosahexaenoic acid (DHA). Recent studies have shown that the DHA/GPR40 signaling pathway may be closely related with adult neurogenesis in the hippocampus. Here, reconstructing pEGFP-N1 vector-expressing GPR40 gene in cultured rat neural stem cells, we demonstrated that DHA-induced neuronal differentiation, neurite growth and branching of adult rat stem cells is mediated at least in part through GPR40 and it remains effective even at low concentrations of DHA. Furthermore, we also revealed that DHA/GPR40 induced the PLC/IP3 signaling pathway and therefore modulated intracellular Ca(2+) mobilization independent of extracellular Ca(2+) concentration. This may be involved in neuronal differentiation and neurite growth in rat neural stem cells transfected with GPR40 gene. These data provide a new sight in the future utilization of neural stem cells transplantation.
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