Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice

Sánchez De La Torre, Aníbal; Aguado Sánchez, Tania; Huerga-Gómez, Alba; Santamaría, Silvia; Gentile, Antonietta; Chara, Juan Carlos; Matute, Carlos; Monory, Krisztina; Mato, Susana; Guzmán Pastor, Manuel; Lutz, Beat; Galve Roperh, Ismael; Palazuelos Diego, Javier

Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice

Cannabinoids are known to modulate oligodendrogenesis and developmental CNS myelination. However, the cell-autonomous action of these compounds on oligodendroglial cells in vivo, and the molecular mechanisms underlying these effects have not yet been studied. Here, by using oligodendroglial precurso...

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Detalhes bibliográficos
Autores:	Sánchez De La Torre, Aníbal, Aguado Sánchez, Tania, Huerga-Gómez, Alba, Santamaría, Silvia, Gentile, Antonietta, Chara, Juan Carlos, Matute, Carlos, Monory, Krisztina, Mato, Susana, Guzmán Pastor, Manuel, Lutz, Beat, Galve Roperh, Ismael, Palazuelos Diego, Javier
Tipo de documento:	artigo
Data de publicação:	2022
País:	España
Recursos:	Universidad Complutense de Madrid (UCM)
Repositório:	Docta Complutense
Idioma:	inglês
OAI Identifier:	oai:docta.ucm.es:20.500.14352/88941
Acesso em linha:	https://hdl.handle.net/20.500.14352/88941
Access Level:	Acceso aberto
Palavra-chave:	615.9 591.18 612.8 Cannabinoid CB1 receptor Oligodendrogenesis Myelination Bioquímica (Biología) Biología molecular (Biología) Neurociencias (Biológicas) 2403 Bioquímica 2407 Biología Celular 2490 Neurociencias

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spelling	Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in miceSánchez De La Torre, AníbalAguado Sánchez, TaniaHuerga-Gómez, AlbaSantamaría, SilviaGentile, AntoniettaChara, Juan CarlosMatute, CarlosMonory, KrisztinaMato, SusanaGuzmán Pastor, ManuelLutz, BeatGalve Roperh, IsmaelPalazuelos Diego, Javier615.9591.18612.8Cannabinoid CB1 receptorOligodendrogenesisMyelinationBioquímica (Biología)Biología molecular (Biología)Neurociencias (Biológicas)2403 Bioquímica2407 Biología Celular2490 NeurocienciasCannabinoids are known to modulate oligodendrogenesis and developmental CNS myelination. However, the cell-autonomous action of these compounds on oligodendroglial cells in vivo, and the molecular mechanisms underlying these effects have not yet been studied. Here, by using oligodendroglial precursor cell (OPC)-targeted genetic mouse models, we show that cannabinoid CB1 receptors exert an essential role in modulating OPC differentiation at the critical periods of postnatal myelination. We found that selective genetic inactivation of CB1 receptors in OPCs in vivo perturbs oligodendrogenesis and postnatal myelination by altering the RhoA/ROCK signaling pathway, leading to hypomyelination, and motor and cognitive alterations in young adult mice. Conversely, pharmacological CB1 receptor activation, by inducing E3 ubiquitin ligase-dependent RhoA proteasomal degradation, promotes oligodendrocyte development and CNS myelination in OPCs, an effect that was not evident in OPC-specific CB1 receptordeficient mice. Moreover, pharmacological inactivation of ROCK in vivo overcomes the defects in oligodendrogenesis and CNS myelination, and behavioral alterations found in OPC-specific CB1 receptor-deficient mice. Overall, this study supports a cellautonomous role for CB1 receptors in modulating oligodendrogenesis in vivo, which may have a profound impact on the scientific knowledge and therapeutic manipulation of CNS myelination by cannabinoids.Springer NatureUniversidad Complutense de Madrid20222022-01-0120222022-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/88941reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/889412026-06-02T12:44:21Z
dc.title.none.fl_str_mv	Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice
title	Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice
spellingShingle	Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice Sánchez De La Torre, Aníbal 615.9 591.18 612.8 Cannabinoid CB1 receptor Oligodendrogenesis Myelination Bioquímica (Biología) Biología molecular (Biología) Neurociencias (Biológicas) 2403 Bioquímica 2407 Biología Celular 2490 Neurociencias
title_short	Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice
title_full	Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice
title_fullStr	Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice
title_full_unstemmed	Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice
title_sort	Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice
dc.creator.none.fl_str_mv	Sánchez De La Torre, Aníbal Aguado Sánchez, Tania Huerga-Gómez, Alba Santamaría, Silvia Gentile, Antonietta Chara, Juan Carlos Matute, Carlos Monory, Krisztina Mato, Susana Guzmán Pastor, Manuel Lutz, Beat Galve Roperh, Ismael Palazuelos Diego, Javier
author	Sánchez De La Torre, Aníbal
author_facet	Sánchez De La Torre, Aníbal Aguado Sánchez, Tania Huerga-Gómez, Alba Santamaría, Silvia Gentile, Antonietta Chara, Juan Carlos Matute, Carlos Monory, Krisztina Mato, Susana Guzmán Pastor, Manuel Lutz, Beat Galve Roperh, Ismael Palazuelos Diego, Javier
author_role	author
author2	Aguado Sánchez, Tania Huerga-Gómez, Alba Santamaría, Silvia Gentile, Antonietta Chara, Juan Carlos Matute, Carlos Monory, Krisztina Mato, Susana Guzmán Pastor, Manuel Lutz, Beat Galve Roperh, Ismael Palazuelos Diego, Javier
author2_role	author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Universidad Complutense de Madrid
dc.subject.none.fl_str_mv	615.9 591.18 612.8 Cannabinoid CB1 receptor Oligodendrogenesis Myelination Bioquímica (Biología) Biología molecular (Biología) Neurociencias (Biológicas) 2403 Bioquímica 2407 Biología Celular 2490 Neurociencias
topic	615.9 591.18 612.8 Cannabinoid CB1 receptor Oligodendrogenesis Myelination Bioquímica (Biología) Biología molecular (Biología) Neurociencias (Biológicas) 2403 Bioquímica 2407 Biología Celular 2490 Neurociencias
description	Cannabinoids are known to modulate oligodendrogenesis and developmental CNS myelination. However, the cell-autonomous action of these compounds on oligodendroglial cells in vivo, and the molecular mechanisms underlying these effects have not yet been studied. Here, by using oligodendroglial precursor cell (OPC)-targeted genetic mouse models, we show that cannabinoid CB1 receptors exert an essential role in modulating OPC differentiation at the critical periods of postnatal myelination. We found that selective genetic inactivation of CB1 receptors in OPCs in vivo perturbs oligodendrogenesis and postnatal myelination by altering the RhoA/ROCK signaling pathway, leading to hypomyelination, and motor and cognitive alterations in young adult mice. Conversely, pharmacological CB1 receptor activation, by inducing E3 ubiquitin ligase-dependent RhoA proteasomal degradation, promotes oligodendrocyte development and CNS myelination in OPCs, an effect that was not evident in OPC-specific CB1 receptordeficient mice. Moreover, pharmacological inactivation of ROCK in vivo overcomes the defects in oligodendrogenesis and CNS myelination, and behavioral alterations found in OPC-specific CB1 receptor-deficient mice. Overall, this study supports a cellautonomous role for CB1 receptors in modulating oligodendrogenesis in vivo, which may have a profound impact on the scientific knowledge and therapeutic manipulation of CNS myelination by cannabinoids.
publishDate	2022
dc.date.none.fl_str_mv	2022 2022-01-01 2022 2022-01-01
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/20.500.14352/88941
url	https://hdl.handle.net/20.500.14352/88941
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Springer Nature
publisher.none.fl_str_mv	Springer Nature
dc.source.none.fl_str_mv	reponame:Docta Complutense instname:Universidad Complutense de Madrid (UCM)
instname_str	Universidad Complutense de Madrid (UCM)
reponame_str	Docta Complutense
collection	Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice

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