RT Journal Article
T1 Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination
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 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.
PB eLife Sciences Publications
SN Electronic: 2050-084X
YR 2020
FD 2020-08-10
LK https://hdl.handle.net/20.500.14352/7941
UL https://hdl.handle.net/20.500.14352/7941
LA eng
NO Unión Europea. Horizonte 2020
NO Unión Europea. FP7
NO Ministerio de Ciencia e Innovación (MICINN)/FEDER
NO Fondation pour la Recherche Médicale
NO Agence Nationale de la Recherche
NO Human Frontier Science Program
DS Docta Complutense
RD 9 may 2025