Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder

Autores
Gasparyan, Ani; Navarro, Daniela; Navarrete, Francisco; Austrich Olivares, Amaya; Scoma, Ernest R.; Hambardikar, Vedangi D.; Acosta, Gabriela Beatriz; Solesio, María E.; Manzanares, Jorge
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fetal alcohol spectrum disorder (FASD) includes neuropsychiatric disturbances related to gestational and lactational ethanol exposure. Available treatments are minimal and do not modulate ethanol-induced damage. Developing animal models simulating FASD is essential for understanding the underlying brain alterations and searching for efficient therapeutic approaches. The main goal of this study was to evaluate the effects of early and chronic cannabidiol (CBD) administration on offspring exposed to an animal model of FASD. Ethanol gavage (3 g/kg/12 h, p.o.) was administered to C57BL/6 J female mice, with a previous history of alcohol consumption, between gestational day 7 and postnatal day 21. On the weaning day, pups were separated by sex, and CBD administration began (30 mg/kg/day, i.p.). After 4–6 weeks of treatment, behavioral and neurobiological changes were analyzed. Mice exposed to the animal model of FASD showed higher anxiogenic and depressive-like behaviors and cognitive impairment that were evaluated through several experimental tests. These behaviors were accompanied by alterations in the gene, cellular and metabolomic targets. CBD administration normalized FASD model-induced emotional and cognitive disturbances, gene expression, and cellular changes with sex-dependent differences. CBD modulates the metabolomic changes detected in the hippocampus and prefrontal cortex. Interestingly, no changes were found in mitochondria or the oxidative status of the cells. These results suggest that the early and repeated administration of CBD modulated the long-lasting behavioral, gene and protein alterations induced by the FASD model, encouraging the possibility of performing clinical trials to evaluate the effects of CBD in children affected with FASD.
Fil: Gasparyan, Ani. Universidad de Miguel Hernández; España. Instituto de Salud Carlos III; España. Instituto de Investigación Sanitaria y Biomédica de Alicante; España
Fil: Navarro, Daniela. Universidad de Miguel Hernández; España. Instituto de Salud Carlos III; España. Instituto de Investigación Sanitaria y Biomédica de Alicante; España
Fil: Navarrete, Francisco. Universidad de Miguel Hernández; España. Instituto de Salud Carlos III; España. Instituto de Investigación Sanitaria y Biomédica de Alicante; España
Fil: Austrich Olivares, Amaya. Universidad de Miguel Hernández; España
Fil: Scoma, Ernest R.. Rutgers University; Estados Unidos
Fil: Hambardikar, Vedangi D.. Rutgers University; Estados Unidos
Fil: Acosta, Gabriela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina
Fil: Solesio, María E.. Rutgers University; Estados Unidos
Fil: Manzanares, Jorge. Universidad de Miguel Hernández; España. Instituto de Salud Carlos III; España. Instituto de Investigación Sanitaria y Biomédica de Alicante; España
Materia
ANIMAL MODEL
CANNABIDIOL
FASD
GENE EXPRESSION
IMMUNOHISTOCHEMISTRY
METABOLOMIC ANALYSES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/218759
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/218759
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorderGasparyan, AniNavarro, DanielaNavarrete, FranciscoAustrich Olivares, AmayaScoma, Ernest R.Hambardikar, Vedangi D.Acosta, Gabriela BeatrizSolesio, María E.Manzanares, JorgeANIMAL MODELCANNABIDIOLFASDGENE EXPRESSIONIMMUNOHISTOCHEMISTRYMETABOLOMIC ANALYSEShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Fetal alcohol spectrum disorder (FASD) includes neuropsychiatric disturbances related to gestational and lactational ethanol exposure. Available treatments are minimal and do not modulate ethanol-induced damage. Developing animal models simulating FASD is essential for understanding the underlying brain alterations and searching for efficient therapeutic approaches. The main goal of this study was to evaluate the effects of early and chronic cannabidiol (CBD) administration on offspring exposed to an animal model of FASD. Ethanol gavage (3 g/kg/12 h, p.o.) was administered to C57BL/6 J female mice, with a previous history of alcohol consumption, between gestational day 7 and postnatal day 21. On the weaning day, pups were separated by sex, and CBD administration began (30 mg/kg/day, i.p.). After 4–6 weeks of treatment, behavioral and neurobiological changes were analyzed. Mice exposed to the animal model of FASD showed higher anxiogenic and depressive-like behaviors and cognitive impairment that were evaluated through several experimental tests. These behaviors were accompanied by alterations in the gene, cellular and metabolomic targets. CBD administration normalized FASD model-induced emotional and cognitive disturbances, gene expression, and cellular changes with sex-dependent differences. CBD modulates the metabolomic changes detected in the hippocampus and prefrontal cortex. Interestingly, no changes were found in mitochondria or the oxidative status of the cells. These results suggest that the early and repeated administration of CBD modulated the long-lasting behavioral, gene and protein alterations induced by the FASD model, encouraging the possibility of performing clinical trials to evaluate the effects of CBD in children affected with FASD.Fil: Gasparyan, Ani. Universidad de Miguel Hernández; España. Instituto de Salud Carlos III; España. Instituto de Investigación Sanitaria y Biomédica de Alicante; EspañaFil: Navarro, Daniela. Universidad de Miguel Hernández; España. Instituto de Salud Carlos III; España. Instituto de Investigación Sanitaria y Biomédica de Alicante; EspañaFil: Navarrete, Francisco. Universidad de Miguel Hernández; España. Instituto de Salud Carlos III; España. Instituto de Investigación Sanitaria y Biomédica de Alicante; EspañaFil: Austrich Olivares, Amaya. Universidad de Miguel Hernández; EspañaFil: Scoma, Ernest R.. Rutgers University; Estados UnidosFil: Hambardikar, Vedangi D.. Rutgers University; Estados UnidosFil: Acosta, Gabriela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Solesio, María E.. Rutgers University; Estados UnidosFil: Manzanares, Jorge. Universidad de Miguel Hernández; España. Instituto de Salud Carlos III; España. Instituto de Investigación Sanitaria y Biomédica de Alicante; EspañaAcademic Press Ltd - Elsevier Science Ltd2023-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/218759Gasparyan, Ani; Navarro, Daniela; Navarrete, Francisco; Austrich Olivares, Amaya; Scoma, Ernest R.; et al.; Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder; Academic Press Ltd - Elsevier Science Ltd; Pharmacological Research; 188; 2-2023; 1-211043-6618CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1043661823000117info:eu-repo/semantics/altIdentifier/doi/10.1016/j.phrs.2023.106655info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:22Zoai:ri.conicet.gov.ar:11336/218759instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:39:23.234CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder
title Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder
spellingShingle Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder
Gasparyan, Ani
ANIMAL MODEL
CANNABIDIOL
FASD
GENE EXPRESSION
IMMUNOHISTOCHEMISTRY
METABOLOMIC ANALYSES
title_short Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder
title_full Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder
title_fullStr Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder
title_full_unstemmed Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder
title_sort Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder
dc.creator.none.fl_str_mv Gasparyan, Ani
Navarro, Daniela
Navarrete, Francisco
Austrich Olivares, Amaya
Scoma, Ernest R.
Hambardikar, Vedangi D.
Acosta, Gabriela Beatriz
Solesio, María E.
Manzanares, Jorge
author Gasparyan, Ani
author_facet Gasparyan, Ani
Navarro, Daniela
Navarrete, Francisco
Austrich Olivares, Amaya
Scoma, Ernest R.
Hambardikar, Vedangi D.
Acosta, Gabriela Beatriz
Solesio, María E.
Manzanares, Jorge
author_role author
author2 Navarro, Daniela
Navarrete, Francisco
Austrich Olivares, Amaya
Scoma, Ernest R.
Hambardikar, Vedangi D.
Acosta, Gabriela Beatriz
Solesio, María E.
Manzanares, Jorge
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANIMAL MODEL
CANNABIDIOL
FASD
GENE EXPRESSION
IMMUNOHISTOCHEMISTRY
METABOLOMIC ANALYSES
topic ANIMAL MODEL
CANNABIDIOL
FASD
GENE EXPRESSION
IMMUNOHISTOCHEMISTRY
METABOLOMIC ANALYSES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Fetal alcohol spectrum disorder (FASD) includes neuropsychiatric disturbances related to gestational and lactational ethanol exposure. Available treatments are minimal and do not modulate ethanol-induced damage. Developing animal models simulating FASD is essential for understanding the underlying brain alterations and searching for efficient therapeutic approaches. The main goal of this study was to evaluate the effects of early and chronic cannabidiol (CBD) administration on offspring exposed to an animal model of FASD. Ethanol gavage (3 g/kg/12 h, p.o.) was administered to C57BL/6 J female mice, with a previous history of alcohol consumption, between gestational day 7 and postnatal day 21. On the weaning day, pups were separated by sex, and CBD administration began (30 mg/kg/day, i.p.). After 4–6 weeks of treatment, behavioral and neurobiological changes were analyzed. Mice exposed to the animal model of FASD showed higher anxiogenic and depressive-like behaviors and cognitive impairment that were evaluated through several experimental tests. These behaviors were accompanied by alterations in the gene, cellular and metabolomic targets. CBD administration normalized FASD model-induced emotional and cognitive disturbances, gene expression, and cellular changes with sex-dependent differences. CBD modulates the metabolomic changes detected in the hippocampus and prefrontal cortex. Interestingly, no changes were found in mitochondria or the oxidative status of the cells. These results suggest that the early and repeated administration of CBD modulated the long-lasting behavioral, gene and protein alterations induced by the FASD model, encouraging the possibility of performing clinical trials to evaluate the effects of CBD in children affected with FASD.
Fil: Gasparyan, Ani. Universidad de Miguel Hernández; España. Instituto de Salud Carlos III; España. Instituto de Investigación Sanitaria y Biomédica de Alicante; España
Fil: Navarro, Daniela. Universidad de Miguel Hernández; España. Instituto de Salud Carlos III; España. Instituto de Investigación Sanitaria y Biomédica de Alicante; España
Fil: Navarrete, Francisco. Universidad de Miguel Hernández; España. Instituto de Salud Carlos III; España. Instituto de Investigación Sanitaria y Biomédica de Alicante; España
Fil: Austrich Olivares, Amaya. Universidad de Miguel Hernández; España
Fil: Scoma, Ernest R.. Rutgers University; Estados Unidos
Fil: Hambardikar, Vedangi D.. Rutgers University; Estados Unidos
Fil: Acosta, Gabriela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina
Fil: Solesio, María E.. Rutgers University; Estados Unidos
Fil: Manzanares, Jorge. Universidad de Miguel Hernández; España. Instituto de Salud Carlos III; España. Instituto de Investigación Sanitaria y Biomédica de Alicante; España
description Fetal alcohol spectrum disorder (FASD) includes neuropsychiatric disturbances related to gestational and lactational ethanol exposure. Available treatments are minimal and do not modulate ethanol-induced damage. Developing animal models simulating FASD is essential for understanding the underlying brain alterations and searching for efficient therapeutic approaches. The main goal of this study was to evaluate the effects of early and chronic cannabidiol (CBD) administration on offspring exposed to an animal model of FASD. Ethanol gavage (3 g/kg/12 h, p.o.) was administered to C57BL/6 J female mice, with a previous history of alcohol consumption, between gestational day 7 and postnatal day 21. On the weaning day, pups were separated by sex, and CBD administration began (30 mg/kg/day, i.p.). After 4–6 weeks of treatment, behavioral and neurobiological changes were analyzed. Mice exposed to the animal model of FASD showed higher anxiogenic and depressive-like behaviors and cognitive impairment that were evaluated through several experimental tests. These behaviors were accompanied by alterations in the gene, cellular and metabolomic targets. CBD administration normalized FASD model-induced emotional and cognitive disturbances, gene expression, and cellular changes with sex-dependent differences. CBD modulates the metabolomic changes detected in the hippocampus and prefrontal cortex. Interestingly, no changes were found in mitochondria or the oxidative status of the cells. These results suggest that the early and repeated administration of CBD modulated the long-lasting behavioral, gene and protein alterations induced by the FASD model, encouraging the possibility of performing clinical trials to evaluate the effects of CBD in children affected with FASD.
publishDate 2023
dc.date.none.fl_str_mv 2023-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/218759
Gasparyan, Ani; Navarro, Daniela; Navarrete, Francisco; Austrich Olivares, Amaya; Scoma, Ernest R.; et al.; Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder; Academic Press Ltd - Elsevier Science Ltd; Pharmacological Research; 188; 2-2023; 1-21
1043-6618
CONICET Digital
CONICET
url http://hdl.handle.net/11336/218759
identifier_str_mv Gasparyan, Ani; Navarro, Daniela; Navarrete, Francisco; Austrich Olivares, Amaya; Scoma, Ernest R.; et al.; Cannabidiol repairs behavioral and brain disturbances in a model of fetal alcohol spectrum disorder; Academic Press Ltd - Elsevier Science Ltd; Pharmacological Research; 188; 2-2023; 1-21
1043-6618
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1043661823000117
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.phrs.2023.106655
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Ltd - Elsevier Science Ltd
publisher.none.fl_str_mv Academic Press Ltd - Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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