Disease-modifying effects of cannabidiol, β-caryophyllene and their combination in Syn1-Cre/Scn1aWT/A1783V mice, a preclinical model of Dravet syndrome

Cannabidiol (CBD) has been recently approved as an antiseizure agent in Dravet Syndrome (DS), a pediatric epileptic encephalopathy, but CBD could also be active against associated comorbidities. Such associated comorbidities were also attenuated by the sesquiterpene β-caryophyllene (BCP). Here, we h...

Full description

Bibliographic Details
Authors: Alonso, Cristina, Satta, Valentina, Hernández Fisac, Inés, Fernández Ruiz, José Javier, Sagredo Ezquioga, Onintza
Format: article
Publication Date:2023
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/103445
Online Access:https://hdl.handle.net/20.500.14352/103445
Access Level:Open access
Keyword:612.015
Dravet syndrome
Cannabinoids
β-caryophyllene
Cannabidiol
Syn1-Cre/Scn1aWT/A1783V mice
LPS-stimulated BV2 cells
Ciencias Biomédicas
2403 Bioquímica
id ES_b9cdb98cb8d24c641dbfd8a31605d889
oai_identifier_str oai:docta.ucm.es:20.500.14352/103445
network_acronym_str ES
network_name_str España
repository_id_str
spelling Disease-modifying effects of cannabidiol, β-caryophyllene and their combination in Syn1-Cre/Scn1aWT/A1783V mice, a preclinical model of Dravet syndromeAlonso, CristinaSatta, ValentinaHernández Fisac, InésFernández Ruiz, José JavierSagredo Ezquioga, Onintza612.015Dravet syndromeCannabinoidsβ-caryophylleneCannabidiolSyn1-Cre/Scn1aWT/A1783V miceLPS-stimulated BV2 cellsCiencias Biomédicas2403 BioquímicaCannabidiol (CBD) has been recently approved as an antiseizure agent in Dravet Syndrome (DS), a pediatric epileptic encephalopathy, but CBD could also be active against associated comorbidities. Such associated comorbidities were also attenuated by the sesquiterpene β-caryophyllene (BCP). Here, we have compared the efficacy of both compounds and further initiated the analysis of a possible additive effect between both compounds in relation with these comorbidities using two experimental approaches. The first experiment was aimed at comparing the benefits of CBD and BCP, including their combination in conditional knock-in Scn1a-A1783V mice, an experimental model of DS, treated since the postnatal day 10th to 24th. As expected, DS mice showed impairment in limb clasping, delay in the appearance of hindlimb grasp reflex and additional behavioural disturbances (e.g., hyperactivity, cognitive deterioration, social interaction deficits). This behavioural impairment was associated with marked astroglial and microglial reactivities in the prefrontal cortex and the hippocampal dentate gyrus. BCP and CBD administered alone were both able to partially attenuate the behavioural disturbances and the glial reactivities, with apparently greater efficacy against glial reactivities obtained with BCP, whereas superior effects in a few specific parameters were obtained when both compounds were combined. In the second experiment, we investigated this additive effect in cultured BV2 cells treated with BCP and/or CBD and stimulated with LPS. As expected, addition of LPS induced a marked increase in several inflammation-related markers (e.g., TLR4, COX-2, iNOS, catalase, TNF-α, IL-1β), as well as elevated Iba-1 immunostaining. Treatment with BCP or CBD attenuated these elevations, but, again and in general, superior results were obtained when both cannabinoids were combined. In conclusion, our results support the interest to continue investigating the combination of BCP and CBD to improve the therapeutic management of DS in relation with their disease- modifying properties.ElsevierUniversidad Complutense de Madrid20232023-01-0120232023-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/103445reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengMinisterio de Sanidad y Consumo Not available CB06%2F05%2F0089 Enfermedades genéticas 89MICIU Not available RTI2018-098885-B-100Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI20%2F00773 ESTUDIO DEL PAPEL DEL RECEPTOR CB2 COMO DIANA TERAPEUTICA EN EL SINDROME DE DRAVETopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1034452026-06-02T12:44:21Z
dc.title.none.fl_str_mv Disease-modifying effects of cannabidiol, β-caryophyllene and their combination in Syn1-Cre/Scn1aWT/A1783V mice, a preclinical model of Dravet syndrome
title Disease-modifying effects of cannabidiol, β-caryophyllene and their combination in Syn1-Cre/Scn1aWT/A1783V mice, a preclinical model of Dravet syndrome
spellingShingle Disease-modifying effects of cannabidiol, β-caryophyllene and their combination in Syn1-Cre/Scn1aWT/A1783V mice, a preclinical model of Dravet syndrome
Alonso, Cristina
612.015
Dravet syndrome
Cannabinoids
β-caryophyllene
Cannabidiol
Syn1-Cre/Scn1aWT/A1783V mice
LPS-stimulated BV2 cells
Ciencias Biomédicas
2403 Bioquímica
title_short Disease-modifying effects of cannabidiol, β-caryophyllene and their combination in Syn1-Cre/Scn1aWT/A1783V mice, a preclinical model of Dravet syndrome
title_full Disease-modifying effects of cannabidiol, β-caryophyllene and their combination in Syn1-Cre/Scn1aWT/A1783V mice, a preclinical model of Dravet syndrome
title_fullStr Disease-modifying effects of cannabidiol, β-caryophyllene and their combination in Syn1-Cre/Scn1aWT/A1783V mice, a preclinical model of Dravet syndrome
title_full_unstemmed Disease-modifying effects of cannabidiol, β-caryophyllene and their combination in Syn1-Cre/Scn1aWT/A1783V mice, a preclinical model of Dravet syndrome
title_sort Disease-modifying effects of cannabidiol, β-caryophyllene and their combination in Syn1-Cre/Scn1aWT/A1783V mice, a preclinical model of Dravet syndrome
dc.creator.none.fl_str_mv Alonso, Cristina
Satta, Valentina
Hernández Fisac, Inés
Fernández Ruiz, José Javier
Sagredo Ezquioga, Onintza
author Alonso, Cristina
author_facet Alonso, Cristina
Satta, Valentina
Hernández Fisac, Inés
Fernández Ruiz, José Javier
Sagredo Ezquioga, Onintza
author_role author
author2 Satta, Valentina
Hernández Fisac, Inés
Fernández Ruiz, José Javier
Sagredo Ezquioga, Onintza
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 612.015
Dravet syndrome
Cannabinoids
β-caryophyllene
Cannabidiol
Syn1-Cre/Scn1aWT/A1783V mice
LPS-stimulated BV2 cells
Ciencias Biomédicas
2403 Bioquímica
topic 612.015
Dravet syndrome
Cannabinoids
β-caryophyllene
Cannabidiol
Syn1-Cre/Scn1aWT/A1783V mice
LPS-stimulated BV2 cells
Ciencias Biomédicas
2403 Bioquímica
description Cannabidiol (CBD) has been recently approved as an antiseizure agent in Dravet Syndrome (DS), a pediatric epileptic encephalopathy, but CBD could also be active against associated comorbidities. Such associated comorbidities were also attenuated by the sesquiterpene β-caryophyllene (BCP). Here, we have compared the efficacy of both compounds and further initiated the analysis of a possible additive effect between both compounds in relation with these comorbidities using two experimental approaches. The first experiment was aimed at comparing the benefits of CBD and BCP, including their combination in conditional knock-in Scn1a-A1783V mice, an experimental model of DS, treated since the postnatal day 10th to 24th. As expected, DS mice showed impairment in limb clasping, delay in the appearance of hindlimb grasp reflex and additional behavioural disturbances (e.g., hyperactivity, cognitive deterioration, social interaction deficits). This behavioural impairment was associated with marked astroglial and microglial reactivities in the prefrontal cortex and the hippocampal dentate gyrus. BCP and CBD administered alone were both able to partially attenuate the behavioural disturbances and the glial reactivities, with apparently greater efficacy against glial reactivities obtained with BCP, whereas superior effects in a few specific parameters were obtained when both compounds were combined. In the second experiment, we investigated this additive effect in cultured BV2 cells treated with BCP and/or CBD and stimulated with LPS. As expected, addition of LPS induced a marked increase in several inflammation-related markers (e.g., TLR4, COX-2, iNOS, catalase, TNF-α, IL-1β), as well as elevated Iba-1 immunostaining. Treatment with BCP or CBD attenuated these elevations, but, again and in general, superior results were obtained when both cannabinoids were combined. In conclusion, our results support the interest to continue investigating the combination of BCP and CBD to improve the therapeutic management of DS in relation with their disease- modifying properties.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-01
2023
2023-01-01
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/20.500.14352/103445
url https://hdl.handle.net/20.500.14352/103445
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Sanidad y Consumo Not available CB06%2F05%2F0089 Enfermedades genéticas 89
MICIU Not available RTI2018-098885-B-100
Instituto de Salud Carlos III http://dx.doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI20%2F00773 ESTUDIO DEL PAPEL DEL RECEPTOR CB2 COMO DIANA TERAPEUTICA EN EL SINDROME DE DRAVET
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/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-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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
_version_ 1869417804128583680
score 15.301603

Similar Items