Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of tuberous sclerosis complex

Serra, I., Scheldeman, C., Bazelot, M., Whalley, B. J., Dallas, M. L. ORCID: https://orcid.org/0000-0002-5190-0522, De Witte, P. A. M. and Williams, C. M. ORCID: https://orcid.org/0000-0003-4452-671X (2019) Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of tuberous sclerosis complex. Behavioural Brain Research, 363. pp. 135-144. ISSN 0166-4328 doi: 10.1016/j.bbr.2019.01.040

Abstract/Summary

Tuberous sclerosis complex (TSC) is a rare disease caused by mutations in the TSC1 or TSC2 genes and is characterized by widespread tumour growth, intractable epilepsy, cognitive deficits and autistic behaviour. CBD has been reported to decrease seizures and inhibit tumour cell progression, therefore we sought to determine the influence of CBD on TSC pathology in zebrafish carrying a nonsense mutation in the tsc2 gene. CBD treatment from 6 to 7 days post-fertilization (dpf) induced significant anxiolytic actions without causing sedation. Furthermore, CBD treatment from 3 dpf had no impact on tsc2-/- larvae motility nor their survival. CBD treatment did, however, reduce the number of phosphorylated rpS6 positive cells, and their cross-sectional cell size. This suggests a CBD mediated suppression of mechanistic target of rapamycin (mTOR) activity in the tsc2-/- larval brain. Taken together, these data suggest that CBD selectively modulates levels of phosphorylated rpS6 in the brain and additionally provides an anxiolytic effect. This is pertinent given the alterations in mTOR signalling in experimental models of TSC. Additional work is necessary to identify upstream signal modulation and to further justify the use of CBD as a possible therapeutic strategy to manage TSC.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/81954
Identification Number/DOI	10.1016/j.bbr.2019.01.040
Refereed	Yes
Divisions	Life Sciences > School of Psychology and Clinical Language Sciences > Department of Psychology Life Sciences > School of Psychology and Clinical Language Sciences > Neuroscience Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Uncontrolled Keywords	tuberous sclerosis complex; cannabidiol; cannabinoids; zebrafish; rpS6; mTOR.
Publisher	Elsevier
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