Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s Disease

Several cannabinoids afforded neuroprotection in experimental models of Huntington’s disease (HD). We investigated whether a 1:1 combination of botanical extracts enriched in either ∆9-tetrahydrocannabinol (∆9-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine...

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Autores: Valdeolivas Rojas, Sara, Sagredo Ezquioga, Onintza, Delgado Wallace, Mercedes, Pozo García, Miguel Ángel, Fernández Ruiz, Javier
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/19209
Acceso en línea:https://hdl.handle.net/20.500.14352/19209
Access Level:acceso abierto
Palabra clave:phytocannabinoids
cannabidiol
Δ9-tetrahydrocannabinol
Huntington’s disease
R6/2 mice
basal ganglia
neuroprotection
Bioquímica (Medicina)
Farmacología (Medicina)
Fisiología
Biología molecular (Farmacia)
Bioquímica (Farmacia)
Farmacología (Farmacia)
2411 Fisiología Humana
3209 Farmacología
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spelling Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s DiseaseValdeolivas Rojas, SaraSagredo Ezquioga, OnintzaDelgado Wallace, MercedesPozo García, Miguel ÁngelFernández Ruiz, JavierphytocannabinoidscannabidiolΔ9-tetrahydrocannabinolHuntington’s diseaseR6/2 micebasal ganglianeuroprotectionBioquímica (Medicina)Farmacología (Medicina)FisiologíaBiología molecular (Farmacia)Bioquímica (Farmacia)Farmacología (Farmacia)2411 Fisiología Humana3209 FarmacologíaSeveral cannabinoids afforded neuroprotection in experimental models of Huntington’s disease (HD). We investigated whether a 1:1 combination of botanical extracts enriched in either ∆9-tetrahydrocannabinol (∆9-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex®, is beneficial in R6/2 mice (a transgenic model of HD), as it was previously shown to have positive effects in neurotoxin-based models of HD. We recorded the progression of neurological deficits and the extent of striatal deterioration, using behavioral, in vivo imaging, and biochemical methods in R6/2 mice and their corresponding wild-type mice. The mice were daily treated, starting at 4 weeks after birth, with a Sativex-like combination of phytocannabinoids (equivalent to 3 mg/kg weight of pure CBD + ∆9-THC) or vehicle. R6/2 mice exhibited the characteristic deterioration in rotarod performance that initiated at 6 weeks and progressed up to 10 weeks, and elevated clasping behavior reflecting dystonia. Treatment with the Sativex-like combination of phytocannabinoids did not recover rotarod performance, but markedly attenuated clasping behavior. The in vivo positron emission tomography (PET) analysis of R6/2 animals at 10 weeks revealed a reduced metabolic activity in the basal ganglia, which was partially attenuated by treatment with the Sativex-like combination of phytocannabinoids. Proton nuclear magnetic resonance spectroscopy (H+-MRS) analysis of the ex vivo striatum of R6/2 mice at 12 weeks revealed changes in various prognostic markers reflecting events typically found in HD patients and animal models, such as energy failure, mitochondrial dysfunction, and excitotoxicity. Some of these changes (taurine/creatine, taurine/N-acetylaspartate, and N-acetylaspartate/choline ratios) were completely reversed by treatment with the Sativex-like combination of phytocannabinoids. A Sativex-like combination of phytocannabinoids administered to R6/2 mice at the onset of motor symptoms produced certain benefits on the progression of striatal deterioration in these mice, which supports the interest of this cannabinoid-based medicine for the treatment of disease progression in HD patients.MDPIUniversidad Complutense de Madrid20172017-03-2320172017-03-23journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/19209reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/192092026-06-02T12:44:21Z
dc.title.none.fl_str_mv Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s Disease
title Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s Disease
spellingShingle Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s Disease
Valdeolivas Rojas, Sara
phytocannabinoids
cannabidiol
Δ9-tetrahydrocannabinol
Huntington’s disease
R6/2 mice
basal ganglia
neuroprotection
Bioquímica (Medicina)
Farmacología (Medicina)
Fisiología
Biología molecular (Farmacia)
Bioquímica (Farmacia)
Farmacología (Farmacia)
2411 Fisiología Humana
3209 Farmacología
title_short Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s Disease
title_full Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s Disease
title_fullStr Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s Disease
title_full_unstemmed Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s Disease
title_sort Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s Disease
dc.creator.none.fl_str_mv Valdeolivas Rojas, Sara
Sagredo Ezquioga, Onintza
Delgado Wallace, Mercedes
Pozo García, Miguel Ángel
Fernández Ruiz, Javier
author Valdeolivas Rojas, Sara
author_facet Valdeolivas Rojas, Sara
Sagredo Ezquioga, Onintza
Delgado Wallace, Mercedes
Pozo García, Miguel Ángel
Fernández Ruiz, Javier
author_role author
author2 Sagredo Ezquioga, Onintza
Delgado Wallace, Mercedes
Pozo García, Miguel Ángel
Fernández Ruiz, Javier
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv phytocannabinoids
cannabidiol
Δ9-tetrahydrocannabinol
Huntington’s disease
R6/2 mice
basal ganglia
neuroprotection
Bioquímica (Medicina)
Farmacología (Medicina)
Fisiología
Biología molecular (Farmacia)
Bioquímica (Farmacia)
Farmacología (Farmacia)
2411 Fisiología Humana
3209 Farmacología
topic phytocannabinoids
cannabidiol
Δ9-tetrahydrocannabinol
Huntington’s disease
R6/2 mice
basal ganglia
neuroprotection
Bioquímica (Medicina)
Farmacología (Medicina)
Fisiología
Biología molecular (Farmacia)
Bioquímica (Farmacia)
Farmacología (Farmacia)
2411 Fisiología Humana
3209 Farmacología
description Several cannabinoids afforded neuroprotection in experimental models of Huntington’s disease (HD). We investigated whether a 1:1 combination of botanical extracts enriched in either ∆9-tetrahydrocannabinol (∆9-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex®, is beneficial in R6/2 mice (a transgenic model of HD), as it was previously shown to have positive effects in neurotoxin-based models of HD. We recorded the progression of neurological deficits and the extent of striatal deterioration, using behavioral, in vivo imaging, and biochemical methods in R6/2 mice and their corresponding wild-type mice. The mice were daily treated, starting at 4 weeks after birth, with a Sativex-like combination of phytocannabinoids (equivalent to 3 mg/kg weight of pure CBD + ∆9-THC) or vehicle. R6/2 mice exhibited the characteristic deterioration in rotarod performance that initiated at 6 weeks and progressed up to 10 weeks, and elevated clasping behavior reflecting dystonia. Treatment with the Sativex-like combination of phytocannabinoids did not recover rotarod performance, but markedly attenuated clasping behavior. The in vivo positron emission tomography (PET) analysis of R6/2 animals at 10 weeks revealed a reduced metabolic activity in the basal ganglia, which was partially attenuated by treatment with the Sativex-like combination of phytocannabinoids. Proton nuclear magnetic resonance spectroscopy (H+-MRS) analysis of the ex vivo striatum of R6/2 mice at 12 weeks revealed changes in various prognostic markers reflecting events typically found in HD patients and animal models, such as energy failure, mitochondrial dysfunction, and excitotoxicity. Some of these changes (taurine/creatine, taurine/N-acetylaspartate, and N-acetylaspartate/choline ratios) were completely reversed by treatment with the Sativex-like combination of phytocannabinoids. A Sativex-like combination of phytocannabinoids administered to R6/2 mice at the onset of motor symptoms produced certain benefits on the progression of striatal deterioration in these mice, which supports the interest of this cannabinoid-based medicine for the treatment of disease progression in HD patients.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-03-23
2017
2017-03-23
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/19209
url https://hdl.handle.net/20.500.14352/19209
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
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
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
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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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score 15,300724

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