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Background <p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting voluntary muscle movement as well as cognitive and other behavioural domains at later disease stages. No effective treatment for ALS is currently available. Elevated neuroinflammation, oxidative stress and alterations to the endocannabinoid system are evident in ALS. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory and anti-oxidant properties. Thus, we evaluated the remedial effects of chronic oral cannabidiol (CBD) treatment on ALS-relevant behavioural domains in the <i>copper-zinc superoxide dismutase 1</i> (<i>SOD1</i>) mouse model of ALS that carries a <i>G93A</i> mutation (<i>SOD1</i><sup><i>G93A</i></sup>).</p> Methods <p>Male and female <i>SOD1</i><sup><i>G93A</i></sup> and wild&#xa0;type-like (WT) littermates were fed either a control (CHOW) or CBD-enriched chow diet (equivalent to a dose of 36 mg/kg per day) beginning from 10 weeks of age. Bodyweight and motor performance were recorded weekly from 11 to 19 weeks and open field behaviours at 12 and 18 weeks. Mice were also tested for prepulse inhibition (PPI), social behaviours, as well as fear-associated memory.</p> Results <p>CBD treatment ameliorated the bodyweight loss in female <i>SOD1</i><sup><i>G93A</i></sup> mice, tended to reinstate sociability in <i>SOD1</i><sup><i>G93A</i></sup> males, strengthened social recognition memory in <i>SOD1</i><sup><i>G93A</i></sup> females, and improved the PPI response in younger <i>SOD1</i><sup><i>G93A</i></sup> females at higher prepulse intensities. CBD had no effect on motor impairments but instead reversed the anxiolytic-like phenotype of 12-week-old male <i>SOD1</i><sup><i>G93A</i></sup> mice and decreased the acoustic startle response and strengthened cue <i>freezing</i> in male mice.</p> Conclusion <p>Thus, the current remedial oral dose of CBD delayed disease progression (inferred by bodyweight) in both male and female mice and improve specific cognitive deficits of <i>SOD1</i><sup><i>G93A</i></sup> mice in a sex specific manner without altering the motor phenotype.</p>

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Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1G93 A) mouse model of amyotrophic lateral sclerosis

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  • 发表日期：

    2025年4月14日

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  • Sandip Ghimire,
  • Fabian Kreilaus,
  • Rossana Rosa Porto,
  • Lyndsey L. Anderson,
  • Justin J. Yerbury,
  • Jonathon C. Arnold,
  • Tim Karl

摘要

Background

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting voluntary muscle movement as well as cognitive and other behavioural domains at later disease stages. No effective treatment for ALS is currently available. Elevated neuroinflammation, oxidative stress and alterations to the endocannabinoid system are evident in ALS. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory and anti-oxidant properties. Thus, we evaluated the remedial effects of chronic oral cannabidiol (CBD) treatment on ALS-relevant behavioural domains in the copper-zinc superoxide dismutase 1 (SOD1) mouse model of ALS that carries a G93A mutation (SOD1G93A).

Methods

Male and female SOD1G93A and wild type-like (WT) littermates were fed either a control (CHOW) or CBD-enriched chow diet (equivalent to a dose of 36 mg/kg per day) beginning from 10 weeks of age. Bodyweight and motor performance were recorded weekly from 11 to 19 weeks and open field behaviours at 12 and 18 weeks. Mice were also tested for prepulse inhibition (PPI), social behaviours, as well as fear-associated memory.

Results

CBD treatment ameliorated the bodyweight loss in female SOD1G93A mice, tended to reinstate sociability in SOD1G93A males, strengthened social recognition memory in SOD1G93A females, and improved the PPI response in younger SOD1G93A females at higher prepulse intensities. CBD had no effect on motor impairments but instead reversed the anxiolytic-like phenotype of 12-week-old male SOD1G93A mice and decreased the acoustic startle response and strengthened cue freezing in male mice.

Conclusion

Thus, the current remedial oral dose of CBD delayed disease progression (inferred by bodyweight) in both male and female mice and improve specific cognitive deficits of SOD1G93A mice in a sex specific manner without altering the motor phenotype.