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Jacobs, J.A., Sehgal, A. (2020). Anandamide Metabolites Protect against Seizures through the TRP Channel Water Witch in Drosophila melanogaster.  Cell Rep. 31(9): 107710.
FlyBase ID
FBrf0245851
Publication Type
Research paper
Abstract

Endocannabinoids protect against seizures, but their mechanism of action is still unclear, as they can have effects independent of known cannabinoid receptors. Using Drosophila melanogaster, which lacks canonical cannabinoid receptors, we report that the endocannabinoids anandamide and 2-arachidonoylglycerol protect against seizures in multiple fly seizure models. Surprisingly, inhibition of anandamide catabolism renders flies insensitive to protection by anandamide, indicating that anandamide metabolites are responsible for seizure protection. Consistent with this finding, arachidonic acid, a direct metabolite of anandamide, protects against seizures. To identify downstream effectors, we test for a role of transient receptor potential (TRP) channels and find that the TRPV1 antagonist capsazepine blocks the protective effect of anandamide. Also, a targeted genetic screen of TRP channels identifies water witch as a mediator of protection by anandamide. Using a Drosophila model, we reveal the role of arachidonic acid in seizure protection and identify a cannabinoid-receptor-1/2-independent mechanism of endocannabinoid seizure protection.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Rep.
    Title
    Cell reports
    ISBN/ISSN
    2211-1247
    Data From Reference