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Molecular and cellular neurosciences v.85, 2017년, pp.148 - 161   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

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

Rojas, P.S.    (Laboratory of Neuroplasticity and Neurogenetics, Faculty of Chemical and Pharmaceutical Sciences, Department of Biochemistry and Molecular Biology, Universidad de Chile, Independencia, 8380492, Chile   ); Aguayo, F.    (Laboratory of Neuroplasticity and Neurogenetics, Faculty of Chemical and Pharmaceutical Sciences, Department of Biochemistry and Molecular Biology, Universidad de Chile, Independencia, 8380492, Chile   ); Neira, D.    (Laboratory of Neuroplasticity and Neurogenetics, Faculty of Chemical and Pharmaceutical Sciences, Department of Biochemistry and Molecular Biology, Universidad de Chile, Independencia, 8380492, Chile   ); Tejos, M.    (Laboratory of Neuroplasticity and Neurogenetics, Faculty of Chemical and Pharmaceutical Sciences, Department of Biochemistry and Molecular Biology, Universidad de Chile, Independencia, 8380492, Chile   ); Aliaga, E.    (Department of Kinesiology, Faculty of Health Sciences, Universidad Católica del Maule, Talca, Chile   ); Muñoz, J.P.    (Laboratory of Neuroplasticity and Neurogenetics, Faculty of Chemical and Pharmaceut  ); Parra, C.S.   Fiedler, J.L.  
  • 초록  

    Abstract Serotonin acts through its receptors (5-HTRs) to shape brain networks during development and modulates essential functions in mature brain. The 5-HT 1A R is mainly located at soma of hippocampal neurons early during brain development and its expression gradually shifts to dendrites during postnatal development. The 5-HT 7 R 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-HT 1A R and 5-HT 7 R 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-HT 7 R increase significantly at 7 DIV. The 5-HT 1A R is preferentially distributed in the soma, while 5-HT 7 R displays a somato-dendritic localization at 7 DIV. Through stimulation with 5-HT at 7 DIV during 24h and using specific antagonists, we determined that 5-HT 1A R decreases the number of primary and secondary dendrites and restricts the growth of primary dendrites. The activation of 5-HT 1A R and 5-HT 7 R 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-HT 1A R restricts dendritogenesis and outgrowth of primary dendrites, but that both 5-HT 1A R and 5-HT 7 R 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. Highlights The protein levels of 5-HT 7 R are increased in hippocampal neurons during DIV. 5-HT reduces significantly the growth of primary dendrites through the activation of 5-HT 1A R. 5-HT 1A R and 5-HT 7 R have a similar action by promoting short secondary dendrites growth. 5-HT 1A R and 5-HT 7 R trigger activation of ERK and AKT which are important signaling molecules involved in dendrite outgrowth. 5-HT 1A R and 5-HT 7 R activation do not promote phosphorylation and inactivation of actin-remodeling protein cofilin.


  • 주제어

    Serotonin .   5-HT1AR .   5-HT7R .   Outgrowth .   Dendrite .   Hippocampal neurons .   ERK1/2 .   AKT .   GSK3β .   LIMK .   Cofilin.  

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