Dataset Information

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

ABSTRACT: 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 Δ9-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 Δ9-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 Δ9-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.

SUBMITTER: Blazquez C

PROVIDER: S-EPMC7417168 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Blázquez Cristina C Ruiz-Calvo Andrea A Bajo-Grañeras Raquel R Baufreton Jérôme M JM Resel Eva E Varilh Marjorie M Pagano Zottola Antonio C AC Mariani Yamuna Y Cannich Astrid A Rodríguez-Navarro José A JA Marsicano Giovanni G Galve-Roperh Ismael I Bellocchio Luigi L Guzmán Manuel M

eLife 20200810

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 Δ<sup>9</sup>-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 ...[more]

PMID: 32773031

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Project description:Objective: Children with autism spectrum disorder (ASD) experience significant challenges with their motor coordination. It is not, however, well understood how motor coordination may impact the behavioral functioning of children with ASD. Therefore the purpose of this study was to explore the relationships between motor coordination and adaptive behavior in 7-12-year-old children with ASD. Methods: Motor coordination was assessed using the Movement Assessment Battery for Children, 2nd Edition (MABC-2) and adaptive behavior was assessed by parental report using the Vineland Adaptive Behavior Scales, 2nd Edition (VABS-2) as part of a larger cross-sectional study. Descriptive characteristics were calculated for MABC-2 and VABS-2 scores and Spearman's rank order correlation analyses were used to examine the relationship between motor coordination and adaptive behavior. Results: On average, the participants (n = 26) exhibited significant challenges in regard to their motor coordination with all but two participants classified as having significant motor impairments by scoring at or below the 16th percentile on the MABC-2. Results from the correlation analyses indicated that manual dexterity was positively related to daily living skills (? = 0.58, p < 0.003), and overall motor coordination was positively related to daily living skills (? = 0.60, p < 0.003) and overall adaptive behavior (? = 0.57, p < 0.003). In all instances, better motor coordination was related to more adaptive behaviors. Conclusion: These results highlight the profound motor coordination challenges that children with ASD experience and also suggest that these challenges, particularly with manual dexterity, are related to the daily behavior of children with ASD. The interrelatedness of motor and adaptive behavior suggests the need to further explore the impact of motor-based interventions for this population, as well as conduct longitudinal studies to disentangle these relationships.

Dataset Information

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

Publications

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

Similar Datasets

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