Regulation of cannabinoid CB1 and CB2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorder

Dysregulations of endocannabinoids and/or cannabinoid (CB) receptors have been implicated in the pathophysiology and treatment of major depressive disorder (MDD). CB1 and CB2 receptors, neuroprotective mTOR (mechanistic target of rapamycin) and pro-apoptotic JNK1/2 (c-Jun-N-terminal kinases) were qu...

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Autores: Salort, Glòria, Hernández-Hernández, Elena, García-Fuster, M Julia, García-Sevilla, Jesús A
Tipo de documento: artigo
Data de publicação:2020
País:España
Recursos:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositório:Docusalut
Idioma:inglês
OAI Identifier:oai:docusalut.com:20.500.13003/21634
Acesso em linha:https://hdl.handle.net/20.500.13003/21634
Access Level:Acceso aberto
Palavra-chave:Receptors, Cannabinoid
Prefrontal Cortex
Depressive Disorder, Major
Humans
TOR Serine-Threonine Kinases
Cannabinoids
Cannabinoides
Trastorno Depresivo Mayor
Humanos
Serina-Treonina Quinasas TOR
Corteza Prefrontal
Receptores de Cannabinoides
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spelling Regulation of cannabinoid CB1 and CB2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorderSalort, GlòriaHernández-Hernández, ElenaGarcía-Fuster, M JuliaGarcía-Sevilla, Jesús AReceptors, CannabinoidPrefrontal CortexDepressive Disorder, MajorHumansTOR Serine-Threonine KinasesCannabinoidsCannabinoidesTrastorno Depresivo MayorHumanosSerina-Treonina Quinasas TORCorteza PrefrontalReceptores de CannabinoidesDysregulations of endocannabinoids and/or cannabinoid (CB) receptors have been implicated in the pathophysiology and treatment of major depressive disorder (MDD). CB1 and CB2 receptors, neuroprotective mTOR (mechanistic target of rapamycin) and pro-apoptotic JNK1/2 (c-Jun-N-terminal kinases) were quantified by immunoblotting in postmortem prefrontal cortex of MDD and controls, and further compared in antidepressant (AD)-free and AD-treated subjects. Neuroplastic proteins (PSD-95, Arc, spinophilin) were quantified in MDD brains. Total cortical CB1 glycosylated (≈54/64 kDa) receptor was increased in MDD (+20%, n=23, p=0.02) when compared with controls (100%, n=19). This CB1 receptor upregulation was quantified in AD-treated (+23%, n=14, p=0.02) but not in AD-free (+14%, n=9, p=0.34) MDD subjects. In the same MDD cortical samples, CB2 glycosylated (≈45 kDa) receptor was unaltered (all MDD: +11%, n=23, p=0.10; AD-free: +12%, n=9, p=0.31; AD-treated: +10%, n=14, p=0.23). In MDD, mTOR activity (p-Ser2448 TOR/t-TOR) was increased (all MDD: +29%, n=18, p=0.002; AD-free: +33%, n=8, p=0.03; AD-treated: +25%, n=10, p=0.04). In contrast, JNK1/2 activity (p-Thr183/Tyr185/t-JNK) was unaltered in MDD subjects. Cortical PSD-95, Arc, and spinophilin contents were unchanged in MDD. A relative limited sample size. Some MDD subjects had been treated with a variety of ADs. The results must be understood in the context of suicide victims with MDD. The upregulation of CB1 receptor density, but not that of CB2 receptor, as well as the increased mTOR activity in PFC/BA9 of subjects with MDD (AD-free/treated) support their contributions in the complex pathophysiology of MDD and in the molecular mechanisms of antidepressant drugs.Elsevier20202020-11-0120202020-11-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/21634reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/216342026-06-22T12:44:07Z
dc.title.none.fl_str_mv Regulation of cannabinoid CB1 and CB2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorder
title Regulation of cannabinoid CB1 and CB2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorder
spellingShingle Regulation of cannabinoid CB1 and CB2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorder
Salort, Glòria
Receptors, Cannabinoid
Prefrontal Cortex
Depressive Disorder, Major
Humans
TOR Serine-Threonine Kinases
Cannabinoids
Cannabinoides
Trastorno Depresivo Mayor
Humanos
Serina-Treonina Quinasas TOR
Corteza Prefrontal
Receptores de Cannabinoides
title_short Regulation of cannabinoid CB1 and CB2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorder
title_full Regulation of cannabinoid CB1 and CB2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorder
title_fullStr Regulation of cannabinoid CB1 and CB2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorder
title_full_unstemmed Regulation of cannabinoid CB1 and CB2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorder
title_sort Regulation of cannabinoid CB1 and CB2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorder
dc.creator.none.fl_str_mv Salort, Glòria
Hernández-Hernández, Elena
García-Fuster, M Julia
García-Sevilla, Jesús A
author Salort, Glòria
author_facet Salort, Glòria
Hernández-Hernández, Elena
García-Fuster, M Julia
García-Sevilla, Jesús A
author_role author
author2 Hernández-Hernández, Elena
García-Fuster, M Julia
García-Sevilla, Jesús A
author2_role author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Receptors, Cannabinoid
Prefrontal Cortex
Depressive Disorder, Major
Humans
TOR Serine-Threonine Kinases
Cannabinoids
Cannabinoides
Trastorno Depresivo Mayor
Humanos
Serina-Treonina Quinasas TOR
Corteza Prefrontal
Receptores de Cannabinoides
topic Receptors, Cannabinoid
Prefrontal Cortex
Depressive Disorder, Major
Humans
TOR Serine-Threonine Kinases
Cannabinoids
Cannabinoides
Trastorno Depresivo Mayor
Humanos
Serina-Treonina Quinasas TOR
Corteza Prefrontal
Receptores de Cannabinoides
description Dysregulations of endocannabinoids and/or cannabinoid (CB) receptors have been implicated in the pathophysiology and treatment of major depressive disorder (MDD). CB1 and CB2 receptors, neuroprotective mTOR (mechanistic target of rapamycin) and pro-apoptotic JNK1/2 (c-Jun-N-terminal kinases) were quantified by immunoblotting in postmortem prefrontal cortex of MDD and controls, and further compared in antidepressant (AD)-free and AD-treated subjects. Neuroplastic proteins (PSD-95, Arc, spinophilin) were quantified in MDD brains. Total cortical CB1 glycosylated (≈54/64 kDa) receptor was increased in MDD (+20%, n=23, p=0.02) when compared with controls (100%, n=19). This CB1 receptor upregulation was quantified in AD-treated (+23%, n=14, p=0.02) but not in AD-free (+14%, n=9, p=0.34) MDD subjects. In the same MDD cortical samples, CB2 glycosylated (≈45 kDa) receptor was unaltered (all MDD: +11%, n=23, p=0.10; AD-free: +12%, n=9, p=0.31; AD-treated: +10%, n=14, p=0.23). In MDD, mTOR activity (p-Ser2448 TOR/t-TOR) was increased (all MDD: +29%, n=18, p=0.002; AD-free: +33%, n=8, p=0.03; AD-treated: +25%, n=10, p=0.04). In contrast, JNK1/2 activity (p-Thr183/Tyr185/t-JNK) was unaltered in MDD subjects. Cortical PSD-95, Arc, and spinophilin contents were unchanged in MDD. A relative limited sample size. Some MDD subjects had been treated with a variety of ADs. The results must be understood in the context of suicide victims with MDD. The upregulation of CB1 receptor density, but not that of CB2 receptor, as well as the increased mTOR activity in PFC/BA9 of subjects with MDD (AD-free/treated) support their contributions in the complex pathophysiology of MDD and in the molecular mechanisms of antidepressant drugs.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-11-01
2020
2020-11-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/21634
url https://hdl.handle.net/20.500.13003/21634
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-NonCommercial-NoDerivatives 4.0 Internacional
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 Internacional
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:Docusalut
instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str Docusalut
collection Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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