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Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of Tuberous Sclerosis Complex

Ines Serra1, Chloë Scheldeman2, Michael Bazelot3

  • 1School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK; School of Pharmacy, University of Reading, Reading, UK.

Behavioural Brain Research
|January 27, 2019
PubMed

Insights

Cannabidiol (CBD) demonstrated anxiolytic effects in zebrafish with tuberous sclerosis complex (TSC) mutations. CBD also reduced key indicators of TSC pathology, suggesting potential therapeutic benefits for this rare genetic disorder.

Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • Tuberous sclerosis complex (TSC) is a rare genetic disorder caused by mutations in TSC1 or TSC2 genes.
  • TSC is characterized by tumor growth, epilepsy, cognitive deficits, and autistic behaviors.
  • Cannabidiol (CBD) shows promise in reducing seizures and inhibiting tumor progression.

Purpose of the Study:

  • To investigate the effects of CBD on TSC pathology in a zebrafish model with a tsc2 gene mutation.
  • To assess CBD's impact on anxiety-like behaviors, motility, and survival in tsc2-/- zebrafish larvae.
  • To determine if CBD modulates mTOR signaling pathway activity in the affected zebrafish brain.

Main Methods:

  • Utilized a zebrafish model with a nonsense mutation in the tsc2 gene.
  • Administered CBD treatment during specific developmental stages (3-7 days post-fertilization).
  • Assessed behavioral changes (anxiety, motility), survival rates, and quantified phosphorylated rpS6 positive cells and cell size in the brain.

Main Results:

  • CBD treatment induced significant anxiolytic effects without causing sedation in tsc2-/- zebrafish.
  • CBD did not negatively impact larval motility or survival rates.
  • CBD treatment reduced the number and size of phosphorylated rpS6 positive cells in the brain, indicating suppressed mTOR activity.

Conclusions:

  • CBD exhibits anxiolytic properties and selectively modulates phosphorylated rpS6 levels in the brain of tsc2-/- zebrafish.
  • These findings suggest CBD may suppress mTOR signaling, a pathway implicated in TSC.
  • Further research is warranted to explore upstream signaling and validate CBD as a potential therapeutic strategy for TSC management.
Keywords:
CannabidiolCannabinoidsTuberous sclerosis complexZebrafishmTORrpS6

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