Dual effect of serotonin on the dendritic growth of cultured hippocampal neurons: Involvement of 5-HT1A and 5-HT7 receptors
Serotonin acts through its receptors (5-HTRs) to shape brain networks during development and modulates essential functions in mature brain. The 5-HT1AR is mainly located at soma of hippocampal neurons early during brain development and its expression gradually shifts to dendrites during postnatal de...
| Autor Principal: | Aliaga-Rojas, Esteban |
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| Otros Autores: | Rojas, P.S., Aguayo, Felipe I., Neira, D., Muñoz, J.P., Tejos-Bravo, Macarena, Parra, Claudio S., Fiedler, Jenny L. |
| Formato: | Artículo |
| Idioma: | English |
| Publicado: |
2017
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| Materias: | |
| Acceso en línea: |
http://repositorio.ucm.cl:8080/handle/ucm/944 |
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| Sumario: |
Serotonin acts through its receptors (5-HTRs) to shape brain networks during development and modulates essential functions in mature brain. The 5-HT1AR is mainly located at soma of hippocampal neurons early during brain development and its expression gradually shifts to dendrites during postnatal development. The 5-HT7R expressed early during hippocampus development, shows a progressive reduction in its expression postnatally. Considering these changes during development, we evaluated in cultured hippocampal neurons whether the 5- HT1AR and 5-HT7R change their expression, modulate dendritic growth, and activate signaling pathways such as ERK1/2, AKT/GSK3β and LIMK/cofilin, which may sustain dendrite outgrowth by controlling cytoskeleton dynamics.
We show that mRNA levels of both receptors increase between 2 and 7 DIV; however only protein levels of 5- HT7R increase significantly at 7 DIV. The 5-HT1AR is preferentially distributed in the soma, while 5-HT7R displays a somato-dendritic localization at 7 DIV. Through stimulation with 5-HT at 7 DIV during 24 h and using specific antagonists, we determined that 5-HT1AR decreases the number of primary and secondary dendrites and restricts the growth of primary dendrites. The activation of 5-HT1AR and 5-HT7R promotes the growth of short secondary dendrites and triggers ERK1/2 and AKT phosphorylation through MEK and PI3K activation respectively; without changes in the phosphorylation of LIMK and cofilin. We conclude that 5-HT1AR restricts dendritogenesis and outgrowth of primary dendrites, but that both 5-HT1AR and 5-HT7R promote secondary dendrite outgrowth. These data support the role of 5-HT in neuronal outgrowth during development and provide insight into cellular basis of neurodevelopmental disorders. |
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