Activation of type 1 cannabinoid receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/109774 https://doi.org/10.1371/journal.pone.0063529 |
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 ([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. |
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Activation of type 1 cannabinoid receptor (CB1R) promotes neurogenesis in murine subventricular zone cell culturesAnimalsArachidonic AcidsBasic Helix-Loop-Helix Transcription FactorsCell DifferentiationCell ProliferationCells, CulturedCerebral VentriclesGABAergic NeuronsGene Expression RegulationImmunohistochemistryMiceMice, Inbred C57BLMultipotent Stem CellsNerve Tissue ProteinsNeuritesNeuronsReceptor, Cannabinoid, CB1Stem CellsNeurogenesisThe 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.Public Library of Science2013info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/109774http://hdl.handle.net/10316/109774https://doi.org/10.1371/journal.pone.0063529eng1932-6203Xapelli, Sara AlvesAgasse, FabienneSardà-Arroyo, LauraBernardino, LilianaSantos, TiagoRibeiro, Filipa F.Valero, JorgeBragança, JoséSchitine, Clarissade Melo Reis, Ricardo ASebastião, Ana M.Malva, João O.info: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:RCAAP2023-10-26T08:57:39Zoai:estudogeral.uc.pt:10316/109774Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:25:55.336011Repositório 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 Alves Animals Arachidonic Acids Basic Helix-Loop-Helix Transcription Factors Cell Differentiation Cell Proliferation Cells, Cultured Cerebral Ventricles GABAergic Neurons Gene Expression Regulation Immunohistochemistry Mice Mice, Inbred C57BL Multipotent Stem Cells Nerve Tissue Proteins Neurites Neurons Receptor, Cannabinoid, CB1 Stem Cells Neurogenesis |
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 Alves |
author_facet |
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. |
author_role |
author |
author2 |
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. |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
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. |
dc.subject.por.fl_str_mv |
Animals Arachidonic Acids Basic Helix-Loop-Helix Transcription Factors Cell Differentiation Cell Proliferation Cells, Cultured Cerebral Ventricles GABAergic Neurons Gene Expression Regulation Immunohistochemistry Mice Mice, Inbred C57BL Multipotent Stem Cells Nerve Tissue Proteins Neurites Neurons Receptor, Cannabinoid, CB1 Stem Cells Neurogenesis |
topic |
Animals Arachidonic Acids Basic Helix-Loop-Helix Transcription Factors Cell Differentiation Cell Proliferation Cells, Cultured Cerebral Ventricles GABAergic Neurons Gene Expression Regulation Immunohistochemistry Mice Mice, Inbred C57BL Multipotent Stem Cells Nerve Tissue Proteins Neurites Neurons Receptor, Cannabinoid, CB1 Stem Cells Neurogenesis |
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 ([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. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013 |
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/10316/109774 http://hdl.handle.net/10316/109774 https://doi.org/10.1371/journal.pone.0063529 |
url |
http://hdl.handle.net/10316/109774 https://doi.org/10.1371/journal.pone.0063529 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1932-6203 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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