Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

Detalhes bibliográficos
Autor(a) principal: Xapelli, Sara
Data de Publicação: 2013
Outros Autores: Agasse, Fabienne, Sarda-Arroyo, Laura, Bernardino, Liliana, Santos, Tiago, Ribeiro, Filipa F., Valero, Jorge, Braganca, José, Schitine, Clarissa, de Melo Reis, Ricardo A., Sebastiao, Ana M., Malva, Joao O.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.1/11739
Resumo: 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 ([Ca2+](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.
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spelling Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell culturesNeural progenitor proliferationCentral-nervous-systemGrowth-factor receptorEndocannabinoid systemStem-cellsAdult neurogenesisNeuronal differentiationP19 CellsBrainPathwayThe 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 ([Ca2+](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.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e TecnologiaPublic Library of ScienceSapientiaXapelli, SaraAgasse, FabienneSarda-Arroyo, LauraBernardino, LilianaSantos, TiagoRibeiro, Filipa F.Valero, JorgeBraganca, JoséSchitine, Clarissade Melo Reis, Ricardo A.Sebastiao, Ana M.Malva, Joao O.2018-12-07T14:57:52Z2013-052013-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/11739eng1932-620310.1371/journal.pone.0063529info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:23:35Zoai:sapientia.ualg.pt:10400.1/11739Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:03:12.142740Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures
title Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures
spellingShingle Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures
Xapelli, Sara
Neural progenitor proliferation
Central-nervous-system
Growth-factor receptor
Endocannabinoid system
Stem-cells
Adult neurogenesis
Neuronal differentiation
P19 Cells
Brain
Pathway
title_short Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures
title_full Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures
title_fullStr Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures
title_full_unstemmed Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures
title_sort Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures
author Xapelli, Sara
author_facet Xapelli, Sara
Agasse, Fabienne
Sarda-Arroyo, Laura
Bernardino, Liliana
Santos, Tiago
Ribeiro, Filipa F.
Valero, Jorge
Braganca, José
Schitine, Clarissa
de Melo Reis, Ricardo A.
Sebastiao, Ana M.
Malva, Joao O.
author_role author
author2 Agasse, Fabienne
Sarda-Arroyo, Laura
Bernardino, Liliana
Santos, Tiago
Ribeiro, Filipa F.
Valero, Jorge
Braganca, José
Schitine, Clarissa
de Melo Reis, Ricardo A.
Sebastiao, Ana M.
Malva, Joao O.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Sapientia
dc.contributor.author.fl_str_mv Xapelli, Sara
Agasse, Fabienne
Sarda-Arroyo, Laura
Bernardino, Liliana
Santos, Tiago
Ribeiro, Filipa F.
Valero, Jorge
Braganca, José
Schitine, Clarissa
de Melo Reis, Ricardo A.
Sebastiao, Ana M.
Malva, Joao O.
dc.subject.por.fl_str_mv Neural progenitor proliferation
Central-nervous-system
Growth-factor receptor
Endocannabinoid system
Stem-cells
Adult neurogenesis
Neuronal differentiation
P19 Cells
Brain
Pathway
topic Neural progenitor proliferation
Central-nervous-system
Growth-factor receptor
Endocannabinoid system
Stem-cells
Adult neurogenesis
Neuronal differentiation
P19 Cells
Brain
Pathway
description 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 ([Ca2+](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.
publishDate 2013
dc.date.none.fl_str_mv 2013-05
2013-05-01T00:00:00Z
2018-12-07T14:57:52Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.1/11739
url http://hdl.handle.net/10400.1/11739
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1932-6203
10.1371/journal.pone.0063529
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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