Cannabidiol and positive effects on object recognition memory in an in vivo model of Fragile X Syndrome: Obligatory role of hippocampal GPR55 receptors
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
38583687
DOI
10.1016/j.phrs.2024.107176
PII: S1043-6618(24)00120-8
Knihovny.cz E-zdroje
- Klíčová slova
- Cannabidiol, Cognitive performance, Fatty acid amide hydrolase, Fragile X syndrome, GPR55 receptors,
- MeSH
- hipokampální oblast CA1 účinky léků metabolismus MeSH
- hipokampus * účinky léků metabolismus MeSH
- kanabidiol * farmakologie terapeutické užití MeSH
- krysa rodu Rattus MeSH
- modely nemocí na zvířatech * MeSH
- paměť účinky léků MeSH
- protein FMRP metabolismus genetika MeSH
- receptory kanabinoidní * metabolismus MeSH
- receptory spřažené s G-proteiny metabolismus MeSH
- rozpoznávání (psychologie) * účinky léků MeSH
- simulace molekulového dockingu MeSH
- syndrom fragilního X * farmakoterapie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Fmr1 protein, rat MeSH Prohlížeč
- GPR55 protein, rat MeSH Prohlížeč
- kanabidiol * MeSH
- protein FMRP MeSH
- receptory kanabinoidní * MeSH
- receptory spřažené s G-proteiny MeSH
Cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, has been recently approved for epileptic syndromes often associated with Autism spectrum disorder (ASD). However, the putative efficacy and mechanism of action of CBD in patients suffering from ASD and related comorbidities remain debated, especially because of the complex pharmacology of CBD. We used pharmacological, immunohistochemical and biochemical approaches to investigate the effects and mechanisms of action of CBD in the recently validated Fmr1-Δexon 8 rat model of ASD, that is also a model of Fragile X Syndrome (FXS), the leading monogenic cause of autism. CBD rescued the cognitive deficits displayed by juvenile Fmr1-Δexon 8 animals, without inducing tolerance after repeated administration. Blockade of CA1 hippocampal GPR55 receptors prevented the beneficial effect of both CBD and the fatty acid amide hydrolase (FAAH) inhibitor URB597 in the short-term recognition memory deficits displayed by Fmr1-Δexon 8 rats. Thus, CBD may exert its beneficial effects through CA1 hippocampal GPR55 receptors. Docking analysis further confirmed that the mechanism of action of CBD might involve competition for brain fatty acid binding proteins (FABPs) that deliver anandamide and related bioactive lipids to their catabolic enzyme FAAH. These findings demonstrate that CBD reduced cognitive deficits in a rat model of FXS and provide initial mechanistic insights into its therapeutic potential in neurodevelopmental disorders.
Bone Physiopathology Research Unit Bambino Gesù Children's Hospital IRCCS Rome Italy
Confocal Microscopy Core Facility Bambino Gesù Children's Hospital IRCCS Rome Italy
Dept Biomedical and Biotechnological Sciences University of Catania Catania Italy
Dept Science Roma Tre University Rome Italy
Histology Core Facility Bambino Gesù Children's Hospital IRCCS Rome Italy
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