Differential Effects of Chronic Ethanol Use on Mouse Neuronal and Astroglial Metabolic Activity

Chronic alcohol use disorder, a major risk factor for the development of neuropsychiatric disorders including addiction to other substances, is associated with several neuropathology including perturbed neuronal and glial activities in the brain. It affects carbon metabolism in specific brain regions, and perturbs neuro-metabolite homeostasis in neuronal and glial cells. Alcohol induced changes in the brain neurochemical profile accompany the negative emotional state associated with dysregulated reward and sensitized stress response to withdrawal. However, the underlying alterations in neuro-astroglial activities and neurochemical dysregulations in brain regions after chronic alcohol use are poorly understood. This study evaluates the impact of chronic ethanol use on the regional neuro-astroglial metabolic activity using H-1-[C-13]-NMR spectroscopy in conjunction with infusion of [1,6-C-13(2)]glucose and sodium [2-C-13]acetate, respectively, after 48 h of abstinence. Besides establishing detailed C-13 labeling of neuro-metabolites in a brain region-specific manner, our results show chronic ethanol induced-cognitive deficits along with a reduction in total glucose oxidation rates in the hippocampus and striatum. Furthermore, using [2-C-13]acetate infusion, we showed an alcohol-induced increase in astroglial metabolic activity in the hippocampus and prefrontal cortex. Interestingly, increased astroglia activity in the hippocampus and prefrontal cortex was associated with a differential expression of monocarboxylic acid transporters that are regulating acetate uptake and metabolism in the brain.

Automated summary

Chronic alcohol use disorder is a major risk factor for neuropsychiatric disorders, and it affects neuronal and glial activities in the brain. The changes in neurochemical profile caused by alcohol are associated with negative emotional state and dysregulated reward. However, the underlying alterations in neuro-astroglial activities and neurochemical dysregulations after chronic alcohol use are poorly understood.