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Title: | Activation of type 1 cannabinoid receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures | Authors: | Xapelli, Sara Alves Agasse, Fabienne Sardà-Arroyo, Laura Bernardino, Liliana Santos, Tiago Ribeiro, Filipa F. Valero, Jorge Bragança, José Schitine, Clarissa de Melo Reis, Ricardo A Sebastião, Ana M. Malva, João O. |
Issue Date: | 2013 | Publisher: | Public Library of Science | Project: | POCTI/SAU-NEU/68465/2006 PTDC/SAU-NEU/ 104415/2008 PTDC/SAU-NEU/101783/2008 POCTI/SAU-NEU/110838/2009 fellowships from Fundação para a Ciência e Tecnologia Fundação Calouste Gulbenkian |
Serial title, monograph or event: | PLoS ONE | Volume: | 8 | Issue: | 5 | Abstract: | The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca(2+)]i) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures. | URI: | https://hdl.handle.net/10316/109774 | ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0063529 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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Activation-of-Type-1-Cannabinoid-Receptor-CB1R-Promotes-Neurogenesis-in-Murine-Subventricular-Zone-Cell-CulturesPLoS-ONE.pdf | 2.81 MB | Adobe PDF | View/Open |
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