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• W3159591229 abstract "BackgroundLittle is known about the targets in the CNS that mediate ethanol analgesia. This study explores the role of spinal astrocyte aldehyde dehydrogenase-2 (ALDH2), a key ethanol-metabolising enzyme, in the analgesic effects of ethanol in mice.MethodsAstrocyte and hepatocyte ALHD2-deficient mice were generated and tested in acute and chronic pain models. Cell-type-specific distribution of ALDH2 was analysed by RNA in situ hybridisation in spinal slices from astrocytic ALDH2-deficient mice and their wild-type littermates. Spinal ethanol metabolites and γ-aminobutyric acid (GABA) content were measured using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry.ResultsALDH2 mRNA was expressed in both astrocytes and neurones in spinal cord slices. Astrocyte ALDH2-deficient mice had decreased expression of ALDH2 mRNA in astrocytes, but not in neurones. Astrocyte ALDH2 deficiency inhibited ethanol-derived acetate, but not acetaldehyde content in spinal cord tissues. Depletion of spinal astrocyte ALDH2 selectively inhibited ethanol-induced anti-nociceptive effect, but not the effect of ethanol, on motor function. Astrocyte ALDH2 deficiency abolished ethanol-induced GABA elevation. The ethanol metabolite acetate produced anti-nociception and increased GABA synthesis in a manner similar to ethanol. I.T. delivery of either GABAA or GABAB receptor antagonists prevented ethanol and acetate-induced analgesia.ConclusionsThese findings provide evidence that ALDH2 in spinal astrocytes mediates spinal ethanol metabolism and ethanol-induced analgesic effects by promoting GABA synthesis and GABAergic transmission in spinal cord." @default.
• W3159591229 created "2021-05-10" @default.
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• W3159591229 date "2021-08-01" @default.
• W3159591229 modified "2023-10-18" @default.
• W3159591229 title "Spinal astrocyte aldehyde dehydrogenase-2 mediates ethanol metabolism and analgesia in mice" @default.
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• W3159591229 doi "https://doi.org/10.1016/j.bja.2021.02.035" @default.
• W3159591229 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8362281" @default.
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