Correction for Woo et al., Control of motor coordination by astrocytic tonic GABA release through modulation of excitation/inhibition balance in cerebellum

Background: Little 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. Methods: Astrocyte 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 ALDH2deficient mice and their wild-type littermates. Spinal ethanol metabolites and g-aminobutyric acid (GABA) content were measured using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. Results: ALDH2 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 GABA A or GABA B receptor antagonists prevented ethanol and acetate-induced analgesia. Conclusions: These 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.

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“…Such astrocytic GABA synthesis mediates tonic GABAergic inhibition and motor function in the cerebellum and hippocampus. 21 , 42 …”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence suggests that both ALDH1a1 and ALDH2 can promote GABA synthesis through putrescine degradation and utilisation pathways in neurones and astrocytes. 20 , 21 …”

mentioning

confidence: 99%

Spinal astrocyte aldehyde dehydrogenase-2 mediates ethanol metabolism and analgesia in mice

Jin

Çınar

et al. 2021

British Journal of Anaesthesia

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Correction for Woo et al., Control of motor coordination by astrocytic tonic GABA release through modulation of excitation/inhibition balance in cerebellum

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Spinal astrocyte aldehyde dehydrogenase-2 mediates ethanol metabolism and analgesia in mice

Spinal astrocyte aldehyde dehydrogenase-2 mediates ethanol metabolism and analgesia in mice

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