Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination
VARILH, Marjorie
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
PAGANO ZOTTOLA, Antonio C.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
MARIANI, Yamuna
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
CANNICH, Astrid
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
MARSICANO, Giovanni
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
BELLOCCHIO, Luigi
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
< Réduire
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Langue
EN
Article de revue
Ce document a été publié dans
Elife. 2020-08-10, vol. 9, p. 1-24
Résumé en anglais
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 ∆9-tetrahydrocannabinol, the ...Lire la suite >
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 ∆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 ∆9-tetrahydrocannabinol-induced impairment of motor coordination in mice. The combination of conditional knockout mouse models and viral vector-mediated autophagy-modulating 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 ∆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. © Blázquez et al.< Réduire
Mots clés en anglais
Autophagy
Cannabinoid
Drug abuse
mTOR
Motor behaviour
Mouse
Neuroscience
Striatum
Projet Européen
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