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Objective This study is to illustrate the effects of CXCL12 on GABA and ACh secretion and its mechanisms.Methods Primary hippocampus neurons were obtained from newborn SD rats.Bilateral hippocampi were carefully dissected and digested in 0.25% trypsin at 37 ℃ for 5 min.Immunocytochemistry were used to determine the location of CXCL12 and its receptor CXCR4.And ELISA was carried to detect the dose of CXCL12 in primary cultures.In addition, GABA and ACh secretion were detected by ELISA under different culture condition, including AMD3100 and CXCL12 stimulation.Results CXCL12 and its receptor CXCR4 mainly located in membrane and cytoplasma, which suggested the role of CXCL12 and its receptor in nervous system.In addition, CXCL12 secretion increased significantly with culture time extension.Moreover, CXCL12 could stimulate ACh secretion and inhibit GABA secretion.But when CXCR4 was knocked down by AMD3100, ACh and GABA secretion changed sharply in an opposite direction.Conclusion CXCL12 may alter GABA and ACh secretion by CXCR4 pathway in cultured hippocampal cells, which may suggest CXCL12 as an important neurotrophic factor to stimulate neurotransmitters releasing.