Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination

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dc.contributor.authorBlázquez Ortiz, Cristina
dc.contributor.authorRuiz-Calvo, Andrea
dc.contributor.authorBajo Grañeras, Raquel
dc.contributor.authorBaufreton, Jérôme M.
dc.contributor.authorResel, Eva
dc.contributor.authorVarilh, Marjorie
dc.contributor.authorPagano Zottola, Antonio C.
dc.contributor.authorMariani, Yamuna
dc.contributor.authorCannich, Astrid
dc.contributor.authorRodríguez-Navarro, José A.
dc.contributor.authorMarsicano, Giovanni
dc.contributor.authorGalve Roperh, Ismael
dc.contributor.authorBellocchio, Luigi
dc.contributor.authorGuzmán Pastor, Manuel
dc.date.accessioned2023-06-17T09:01:09Z
dc.date.available2023-06-17T09:01:09Z
dc.date.issued2020-08-10
dc.description.abstractThe use of cannabis is rapidly expanding worldwide. Thus, innovative studies aimed to identify, understand and potentially reduce cannabis-evoked harms are warranted. Here, we found that D 9 -tetrahydrocannabinol, the psychoactive ingredient of cannabis, disrupts autophagy selectively in the striatum, a brain area that controls motor behavior, both in vitro and in vivo. Boosting autophagy, either pharmacologically (with temsirolimus) or by dietary intervention (with trehalose), rescued the D 9 -tetrahydrocannabinol-induced impairment of motor coordination in mice. The combination of conditional knockout mouse models and viral vector-mediated autophagymodulating strategies in vivo showed that cannabinoid CB1 receptors located on neurons belonging to the direct (striatonigral) pathway are required for the motor-impairing activity of D 9 - tetrahydrocannabinol by inhibiting local autophagy. Taken together, these findings identify inhibition of autophagy as an unprecedented mechanistic link between cannabinoids and motor performance, and suggest that activators of autophagy might be considered as potential therapeutic tools to treat specific cannabinoid-evoked behavioral alterations.
dc.description.departmentSección Deptal. de Bioquímica y Biología Molecular (Biológicas)
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.sponsorshipUnión Europea. Horizonte 2020
dc.description.sponsorshipUnión Europea. FP7
dc.description.sponsorshipMinisterio de Ciencia e Innovación (MICINN)/FEDER
dc.description.sponsorshipFondation pour la Recherche Médicale
dc.description.sponsorshipAgence Nationale de la Recherche
dc.description.sponsorshipHuman Frontier Science Program
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/64568
dc.identifier.doi10.7554/eLife.56811
dc.identifier.issnElectronic: 2050-084X
dc.identifier.officialurlhttps://elifesciences.org/articles/56811
dc.identifier.urihttps://hdl.handle.net/20.500.14352/7941
dc.issue.numbere56811
dc.journal.titleeLife
dc.language.isoeng
dc.page.final24
dc.page.initial1
dc.publishereLife Sciences Publications
dc.relation.projectIDCannaPreg (640923); MiCaBra (786467)
dc.relation.projectIDENDOFOOD (260515)
dc.relation.projectID(SAF2015-64945-R, RTI2018-095311-B-I00, SAF2016-78666-R)
dc.relation.projectID(DRM20101220445, DPP20151033974, ARF20140129235)
dc.relation.projectIDANR-16-CE37-0010-01, ANR 18-CE16-0001-02, ANR-10-LABX-0043, ANR-18-CE14-0029-01, ANR-19-CE14)
dc.relation.projectID(RGP0036/2014)
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.cdu615.9
dc.subject.cdu577.1
dc.subject.cdu615.9
dc.subject.keywordAutophagy
dc.subject.keywordCannabinoid
dc.subject.keywordDrug abuse
dc.subject.keywordmTOR
dc.subject.keywordMotor behaviour
dc.subject.keywordMouse
dc.subject.keywordNeuroscience
dc.subject.keywordStriatum
dc.subject.ucmBioquímica (Biología)
dc.subject.ucmNeurociencias (Biológicas)
dc.subject.unesco2302 Bioquímica
dc.subject.unesco2490 Neurociencias
dc.titleInhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination
dc.typejournal article
dc.volume.number9
dspace.entity.typePublication
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relation.isAuthorOfPublication5795a7c4-d0fd-45f4-a94f-c721af6fe686
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