DHA promotes the neuronal differentiation of rat neural stem cells transfected with GPR40 gene.
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.
Ma
Dexuan
D
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Zhang
Minmin
M
Larsen
Christian P
CP
Xu
Feng
F
Hua
Wei
W
Yamashima
Tetsumori
T
Mao
Ying
Y
Zhou
Liangfu
L
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D002491:Central Nervous System Agents; C473035:G-protein-coupled receptor 40, rat; D043562:Receptors, G-Protein-Coupled; D004281:Docosahexaenoic Acids; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium