title: Serotonin (5-HT) regulates neurite outgrowth through 5-HT1A and 5-HT7 receptors in cultured hippocampal neurons.
abstract: Serotonin (5-HT) production and expression of 5-HT receptors (5-HTRs) occur early during prenatal development. Recent evidence suggests that, in addition to its classical role as a neurotransmitter, 5-HT regulates neuronal connectivity during mammalian development by modulating cell migration and neuronal cytoarchitecture. Given the variety of 5-HTRs, researchers have had difficulty clarifying the specific role of each receptor subtype in brain development. Signalling mediated by the G-protein-coupled 5-HT1A R and 5-HT7 R, however, has been associated with neuronal plasticity. Thus, we hypothesized that 5-HT promotes neurite outgrowth through 5-HT1A R and 5-HT7 R. The involvement of 5-HT1A R and 5-HT7 R in the morphology of rat hippocampal neurons was evaluated by treating primary cultures at 2 days in vitro with 5-HT and specific antagonists for 5-HT1A R and 5-HT7 R (WAY-100635 and SB269970, respectively). The stimulation of hippocampal neurons with 100 nM 5-HT for 24 hr produced no effect on either the number or the length of primary neurites. Nonetheless, after 5HT7 R was blocked, the addition of 5-HT increased the number of primary neurites, suggesting that 5HT7 R could inhibit neuritogenesis. In contrast, 5-HT induced secondary neurite outgrowth, an effect inhibited by 1 μM WAY-100635 or SB269970. These results suggest that both serotonergic receptors participate in secondary neurite outgrowth. We conclude that 5-HT1A R and 5-HT7 R regulate neuronal morphology in primary hippocampal cultures by promoting secondary neurite outgrowth.
authors.affiliation: Laboratory of Neuroplasticity and Neurogenetics, Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago, Chile.
authors.forename: Paulina S
authors.initials: PS
authors.lastname: Rojas
authors.forename: David
authors.initials: D
authors.lastname: Neira
authors.forename: Mauricio
authors.initials: M
authors.lastname: Muñoz
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandero
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Fiedler
mesh_terms: D000818:Animals; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D010636:Phenols; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; C404922:SB 269970; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
keywords: 5-HT1A receptor; 5-HT7 receptor; culture; hippocampus; neurites; neuron; outgrowth; serotonin