The serine hydrolase ABHD6 controls survival and thermally induced seizures in a mouse model of Dravet syndrome.

ABSTRACT: Evidence suggests that inhibition of α/β hydrolase-domain containing 6 (ABHD6) reduces seizures; however, the molecular mechanism of this therapeutic response remains unknown. We discovered that heterozygous expression of Abhd6 (Abhd6^+/-) significantly reduced the premature lethality of Scn1a^+/- mouse pups, a genetic mouse model of Dravet Syndrome (DS). Both Abhd6^+/- mutation and pharmacological inhibition of ABHD6 reduced the duration and incidence of thermally induced seizures in Scn1a^+/- pups. Mechanistically, the in vivo anti-seizure response resulting from ABHD6 inhibition is mediated by potentiation of gamma-aminobutyric acid receptors Type-A (GABA_AR). Brain slice electrophysiology showed that blocking ABHD6 potentiates extrasyna

SUBMITTER: Westenbroek R 

PROVIDER: S-EPMC10332637 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature