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

• Published in: Neurochemical research Vol. 48; no. 8; pp. 2580 - 2594
• Main Authors: Bhat, Unis Ahmad, Kumar, Sreemantula Arun, Chakravarty, Sumana, Patel, Anant Bahadur, Kumar, Arvind
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2023; Springer Nature B.V
• Subjects: Acetic acid; Addictions; Alcohol use; Alcohols; Astrocytes; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain; Cell Biology; Cognitive ability; Ethanol; Glial cells; Glucose; Hippocampus; Homeostasis; Magnetic resonance spectroscopy; Mental disorders; Metabolism; Metabolites; Neostriatum; Neurochemistry; Neurology; Neuronal-glial interactions; Neurosciences; NMR spectroscopy; Original Paper; Oxidation; Prefrontal cortex; Risk factors; Withdrawal; C NMR spectroscopy; Monocarboxylic acid transporters; Alcohol abuse; Brain metabolism; Astrocytes; Neurons; GABA; Glutamate; 13C NMR spectroscopy
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-023-03922-y

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 1 H-[ 13 C]-NMR spectroscopy in conjunction with infusion of [1,6- 13 C 2 ]glucose and sodium [2- 13 C]acetate, respectively, after 48 h of abstinence. Besides establishing detailed 13 C 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- 13 C]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.