RT Journal Article
T1 Cannabinoid-induced motor dysfunction via autophagy inhibition
A1 Blázquez Ortiz, Cristina
A1 Ruiz Calvo, Andrea
A1 Bajo Grañeras, Raquel
A1 Baufreton, Jérôme M.
A1 Resel, Eva
A1 Varilh, Marjorie
A1 Pagano Zottola, Antonio C.
A1 Mariani, Yamuna
A1 Cannich, Astrid
A1 Rodríguez Navarro, José A.
A1 Marsicano, Giovanni
A1 Galve Roperh, Ismael
A1 Bellocchio, Luigi
A1 Guzmán Pastor, Manuel
AB The recreational and medical use of cannabis is largely increasing worldwide. Cannabis use, however, can cause adverse side effects, so conducting innovative studies aimed to understand and potentially reduce cannabis-evoked harms is important. Previous research conducted on cultured neural cells had supported that CNR1/CB1R (cannabinoid receptor 1), the main molecular target of cannabis, affects macroautophagy/autophagy. However, it was not known whether CNR1 controls autophagy in the brain in vivo, and, eventually, what the functional consequences of a potential CNR1-autophagy connection could be. We have now found that Δ9-tetrahydrocannabinol (THC), the major intoxicating constituent of cannabis, impairs autophagy in the mouse striatum. Administration of autophagy activators (specifically, the rapalog temsirolimus and the disaccharide trehalose) rescues THC-induced autophagy inhibition and motor dyscoordination. The combination of various genetic strategies in vivo supports the idea that CNR1 molecules located on neurons belonging to the direct (striatonigral) pathway are required for the autophagy- and motor-impairing activity of THC. By identifying autophagy as a mechanistic link between THC and motor performance, our findings may open a new conceptual view on how cannabis acts in the brain.
PB Taylor & Francis
SN 1554-8635
YR 2020
FD 2020-10-20
LK https://hdl.handle.net/20.500.14352/8017
UL https://hdl.handle.net/20.500.14352/8017
LA eng
NO Unión Europea. Horizonte 2020
NO Unión Europea. FP7
NO Ministerio de Ciencia e Innovación (MICINN)/FEDER
NO Human Frontiers Science Program
NO Region Nouvelle Aquitaine; Agence Nationale de la Recherche
NO Fondation pour la Recherche Medicale
NO Institut national de la santé et de la recherche médicale (INSERM)
DS Docta Complutense
RD 6 abr 2025