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Serotonin (5-HT) functions as a chemoattractant that modulates neural migration during prenatal and early postnatal development. However, its molecular mechanism remains to be elucidated. The effect of 5-HT on neural cell migration was examined using PC12 neuron-like cell line. Transwell migration assay was used to determine the effect of 5-HT on PC12 cell migration. The results demonstrated that 5-HT and nerve growth factor (NGF) induced PC12 cell migration in a dose-dependent manner. Additionally, 5-HT receptor antagonists suggest that 5-HT-induced migration was mediated by serotonin receptor 6 (5-HT 6 ), a Gs-protein coupled receptor that elevates the intercellular cAMP level. By contrast, antagonists of serotonin receptor 3 (5-HT 3 ) did not show any effects on PC12 cell migration. Clozapine, an inhibitor of cAMP accumulation mediated by 5-HT 6 , significantly reduced the effect of 5-HT on the PC12 cell migration. An inhibitor of extracellular signal-regulated kinase (ERK) also suppressed migration. These results suggest that 5-HT induces PC12 cell migration by activating cAMP/ERK signaling pathways, which is mediated by 5-HT 6 receptor.

Serotonin induces the migration of PC12 cells via the serotonin receptor 6/cAMP/ERK pathway