5-Hydroxytryptamine 1A and 2B Serotonin Receptors in Neurite Outgrowth: Involvement of Early Growth Response Protein 1

Neurotransmitters play important roles in neurogenesis; in particular, acetylcholine and serotonin may regulate neurite elongation. Acetylcholine may also activate transcription factors such as early growth response protein 1 (EGR-1), which plays a role in neurite extension. N18TG2 neuroblastoma cel...

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Veröffentlicht in:Developmental neuroscience 2013-12, Vol.35 (6), p.450-460
Hauptverfasser: Anelli, Tonino, Cardarelli, Silvia, Ori, Michela, Nardi, Irma, Biagioni, Stefano, Poiana, Giancarlo
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Sprache:eng
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Zusammenfassung:Neurotransmitters play important roles in neurogenesis; in particular, acetylcholine and serotonin may regulate neurite elongation. Acetylcholine may also activate transcription factors such as early growth response protein 1 (EGR-1), which plays a role in neurite extension. N18TG2 neuroblastoma cells (which do not produce neurotransmitters and constitutively express muscarinic acetylcholine receptors) were transfected with constructs containing the cDNA for choline acetyltransferase, 5-hydroxytryptamine 1A (5-HT 1A ) and 5-HT 2B serotonin receptors to study acetylcholine and serotonin interplay in neurite outgrowth. 5-HT 1A receptor stimulation causes a decrease in EGR-1 levels and inhibition of neurite outgrowth; 5-HT 2B stimulation, however, has no effect. Muscarinic cholinergic stimulation, on the other end, increases EGR-1 levels and fiber outgrowth. Inhibition of EGR-1 binding reduces fiber outgrowth activity. When both cholinergic and 5-HT 1A receptors are stimulated, fiber outgrowth is restored; therefore, acetylcholine counterbalances the inhibitory effect of serotonin on neurite outgrowth. These results suggest that EGR-1 plays a role in the interplay of acetylcholine and serotonin in the regulation of neurite extension during development.
ISSN:0378-5866
1421-9859
DOI:10.1159/000354423