A combination of Δ9-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's disease

A combination of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) at non-psychoactive doses was previously demonstrated to reduce cognitive decline in APP/PS1 mice, an animal model of Alzheimer's disease (AD). However, the neurobiological substrates underlying these therapeutic properties...

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Autores: Köfalvi, Attila, Sánchez Fernández, Nuria, Gómez Acero, Laura, Castañé, Anna, Adell, Albert, Campa, Leticia, Bonaventura, Jordi, Brito, Verónica, Ginés Padrós, Silvia, Queiróz, Francisco, Silva, Henrique, Lopes, João Pedro, Lopes, Cátia R., Radosevic, Marija, Gasull Casanova, Xavier, Cunha, Rodrigo A., Ferreira, Samira G., Ciruela Alférez, Francisco, Aso Pérez, Ester
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/216359
Acceso en línea:https://hdl.handle.net/2445/216359
Access Level:acceso abierto
Palabra clave:Àcid glutàmic
Hipocamp (Cervell)
Malaltia d'Alzheimer
Cànnabis
Glutamic acid
Hippocampus (Brain)
Alzheimer's disease
Cannabis
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spelling A combination of Δ9-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's diseaseKöfalvi, AttilaSánchez Fernández, NuriaGómez Acero, LauraCastañé, AnnaAdell, AlbertCampa, LeticiaBonaventura, JordiBrito, VerónicaGinés Padrós, SilviaQueiróz, FranciscoSilva, HenriqueLopes, João PedroLopes, Cátia R.Radosevic, MarijaGasull Casanova, XavierCunha, Rodrigo A.Ferreira, Samira G.Ciruela Alférez, FranciscoAso Pérez, EsterÀcid glutàmicHipocamp (Cervell)Malaltia d'AlzheimerCànnabisGlutamic acidHippocampus (Brain)Alzheimer's diseaseCannabisA combination of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) at non-psychoactive doses was previously demonstrated to reduce cognitive decline in APP/PS1 mice, an animal model of Alzheimer's disease (AD). However, the neurobiological substrates underlying these therapeutic properties of Δ9-THC and CBD are not fully understood. Considering that dysregulation of glutamatergic activity contributes to cognitive impairment in AD, the present study evaluates the hypothesis that the combination of these two natural cannabinoids might reverse the alterations in glutamate dynamics within the hippocampus of this animal model of AD. Interestingly, our findings reveal that chronic treatment with Δ9-THC and CBD, but not with any of them alone, reduces extracellular glutamate levels and the basal excitability of the hippocampus in APP/PS1 mice. These effects are not related to significant changes in the function and structure of glutamate synapses, as no relevant changes in synaptic plasticity, glutamate signaling or in the levels of key components of these synapses were observed in cannabinoid-treated mice. Our data instead indicate that these cannabinoid effects are associated with the control of glutamate uptake and/or to the regulation of the hippocampal network. Taken together, these results support the potential therapeutic properties of combining these natural cannabinoids against the excitotoxicity that occurs in AD brains.Springer Verlag2024202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion11 p.application/pdfhttps://hdl.handle.net/2445/216359Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.neurot.2024.e00439Neurotherapeutics, 2024, vol. 21, num.5https://doi.org/10.1016/j.neurot.2024.e00439cc by-nc-nd (c) Köfalvi, Attila et al., 2024https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2163592026-05-29T05:05:01Z
dc.title.none.fl_str_mv A combination of Δ9-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's disease
title A combination of Δ9-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's disease
spellingShingle A combination of Δ9-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's disease
Köfalvi, Attila
Àcid glutàmic
Hipocamp (Cervell)
Malaltia d'Alzheimer
Cànnabis
Glutamic acid
Hippocampus (Brain)
Alzheimer's disease
Cannabis
title_short A combination of Δ9-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's disease
title_full A combination of Δ9-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's disease
title_fullStr A combination of Δ9-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's disease
title_full_unstemmed A combination of Δ9-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's disease
title_sort A combination of Δ9-tetrahydrocannabinol and cannabidiol modulates glutamate dynamics in the hippocampus of an animal model of Alzheimer's disease
dc.creator.none.fl_str_mv Köfalvi, Attila
Sánchez Fernández, Nuria
Gómez Acero, Laura
Castañé, Anna
Adell, Albert
Campa, Leticia
Bonaventura, Jordi
Brito, Verónica
Ginés Padrós, Silvia
Queiróz, Francisco
Silva, Henrique
Lopes, João Pedro
Lopes, Cátia R.
Radosevic, Marija
Gasull Casanova, Xavier
Cunha, Rodrigo A.
Ferreira, Samira G.
Ciruela Alférez, Francisco
Aso Pérez, Ester
author Köfalvi, Attila
author_facet Köfalvi, Attila
Sánchez Fernández, Nuria
Gómez Acero, Laura
Castañé, Anna
Adell, Albert
Campa, Leticia
Bonaventura, Jordi
Brito, Verónica
Ginés Padrós, Silvia
Queiróz, Francisco
Silva, Henrique
Lopes, João Pedro
Lopes, Cátia R.
Radosevic, Marija
Gasull Casanova, Xavier
Cunha, Rodrigo A.
Ferreira, Samira G.
Ciruela Alférez, Francisco
Aso Pérez, Ester
author_role author
author2 Sánchez Fernández, Nuria
Gómez Acero, Laura
Castañé, Anna
Adell, Albert
Campa, Leticia
Bonaventura, Jordi
Brito, Verónica
Ginés Padrós, Silvia
Queiróz, Francisco
Silva, Henrique
Lopes, João Pedro
Lopes, Cátia R.
Radosevic, Marija
Gasull Casanova, Xavier
Cunha, Rodrigo A.
Ferreira, Samira G.
Ciruela Alférez, Francisco
Aso Pérez, Ester
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Àcid glutàmic
Hipocamp (Cervell)
Malaltia d'Alzheimer
Cànnabis
Glutamic acid
Hippocampus (Brain)
Alzheimer's disease
Cannabis
topic Àcid glutàmic
Hipocamp (Cervell)
Malaltia d'Alzheimer
Cànnabis
Glutamic acid
Hippocampus (Brain)
Alzheimer's disease
Cannabis
description A combination of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) at non-psychoactive doses was previously demonstrated to reduce cognitive decline in APP/PS1 mice, an animal model of Alzheimer's disease (AD). However, the neurobiological substrates underlying these therapeutic properties of Δ9-THC and CBD are not fully understood. Considering that dysregulation of glutamatergic activity contributes to cognitive impairment in AD, the present study evaluates the hypothesis that the combination of these two natural cannabinoids might reverse the alterations in glutamate dynamics within the hippocampus of this animal model of AD. Interestingly, our findings reveal that chronic treatment with Δ9-THC and CBD, but not with any of them alone, reduces extracellular glutamate levels and the basal excitability of the hippocampus in APP/PS1 mice. These effects are not related to significant changes in the function and structure of glutamate synapses, as no relevant changes in synaptic plasticity, glutamate signaling or in the levels of key components of these synapses were observed in cannabinoid-treated mice. Our data instead indicate that these cannabinoid effects are associated with the control of glutamate uptake and/or to the regulation of the hippocampal network. Taken together, these results support the potential therapeutic properties of combining these natural cannabinoids against the excitotoxicity that occurs in AD brains.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/216359
url https://hdl.handle.net/2445/216359
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.neurot.2024.e00439
Neurotherapeutics, 2024, vol. 21, num.5
https://doi.org/10.1016/j.neurot.2024.e00439
dc.rights.none.fl_str_mv cc by-nc-nd (c) Köfalvi, Attila et al., 2024
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Köfalvi, Attila et al., 2024
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11 p.
application/pdf
dc.publisher.none.fl_str_mv Springer Verlag
publisher.none.fl_str_mv Springer Verlag
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869403126190047232
score 15.811543

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