Serotonin (5-HT) regulates the development of cerebral cortex, but 5-HT receptors mediating the effects are poorly understood. We investigated roles of 5-HT2A receptor in dendritic growth cones using dissociation culture of rat cerebral cortex. Neurons at embryonic day 16 were cultured for 4 days and treated with 5-HT2A/2C receptor agonist (DOI) for 4h. DOI increased the size of growth cone periphery which was actin-rich and microtubule-associated protein 2-negative at the dendritic tip. The length increase of the growth cone periphery may be mediated by 5-HT2A receptor, because the 5-HT2A receptor antagonist reversed the effects of DOI. Moreover, the time-lapse analysis demonstrated the increase of morphological dynamics in dendritic growth cones by DOI. Next, to elucidate the mechanisms underlying the actions of 5-HT2A receptor in dendritic growth cones, we examined the cytoskeletal proteins, tyrosinated ?-tubulin (Tyr-T; dynamic tubulin) and acetylated ?-tubulin (Ace-T; stable tubulin). DOI increased the fluorescence intensity of Tyr-T, while decreased that of Ace-T in the dendritic growth cone periphery. These effects were reversed by the 5-HT2A receptor antagonist, suggesting that 5-HT2A receptor promotes microtubule dynamics. In summary, it was suggested that 5-HT2A receptor induces morphological changes and dynamics of dendritic growth cones through regulation of microtubule assembly.
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