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., de Witte, P.A.M., Williams, C.M.
- Behavioural brain research 363: 135-144 (Journal)
- Registered Authors
- cannabidiol, cannabinoids, mTOR, rpS6, tuberous sclerosis complex, zebrafish
- MeSH Terms
- Disease Models, Animal
- Intracellular Signaling Peptides and Proteins/drug effects
- Intracellular Signaling Peptides and Proteins/genetics
- Locomotion/drug effects
- Phosphorylation/drug effects
- Ribosomal Protein S6/drug effects*
- Signal Transduction/drug effects
- TOR Serine-Threonine Kinases/drug effects
- Tuberous Sclerosis/drug therapy*
- Tuberous Sclerosis/physiopathology
- Tuberous Sclerosis Complex 2 Protein/genetics
- Tuberous Sclerosis Complex 2 Protein/metabolism
- Zebrafish Proteins/drug effects
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- 30684511 Full text @ Behav. Brain Res.
Serra, I., Scheldeman, C., Bazelot, M., Whalley, B.J., Dallas, M.L., de Witte, P.A.M., Williams, C.M. (2019) Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of Tuberous Sclerosis Complex. Behavioural brain research. 363:135-144.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes