Dual effect of serotonin on the dendritic growth of cultured hippocampal neurons: Involvement of 5-HT1A and 5-HT7 receptors

dc.creatorAliaga-Rojas, Esteban
dc.creatorRojas, P.S.
dc.creatorAguayo, Felipe I.
dc.creatorNeira, D.
dc.creatorMuñoz, J.P.
dc.creatorTejos-Bravo, Macarena
dc.creatorParra, Claudio S.
dc.creatorFiedler, Jenny L.
dc.date2017-10-30T15:20:49Z
dc.date2017-10-30T15:20:49Z
dc.date2017
dc.date.accessioned2019-11-20T15:09:24Z
dc.date.available2019-11-20T15:09:24Z
dc.identifierhttp://repositorio.ucm.cl:8080/handle/ucm/944
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/3032687
dc.descriptionSerotonin 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.
dc.languageen
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.sourceMolecular and Cellular Neuroscience, 85, 148–161
dc.subjectSerotonin
dc.subject5-HT1AR
dc.subject5-HT7R
dc.subjectOutgrowth
dc.subjectDendrite
dc.subjectHippocampal neurons
dc.subjectERK1/2
dc.subjectAKT
dc.subjectGSK3β
dc.subjectLIMK
dc.subjectCofilin
dc.titleDual effect of serotonin on the dendritic growth of cultured hippocampal neurons: Involvement of 5-HT1A and 5-HT7 receptors
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución