Epigenetics and Neuropsychiatric Disorders Laboratory, CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Habsiguda, Hyderabad, Telangana State (TS), 500007, India.
Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, India.
Neurochem Res. 2023 Aug;48(8):2580-2594. doi: 10.1007/s11064-023-03922-y. Epub 2023 Apr 17.
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-[C]-NMR spectroscopy in conjunction with infusion of [1,6-C]glucose and sodium [2-C]acetate, respectively, after 48 h of abstinence. Besides establishing detailed 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-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.
慢性酒精使用障碍是神经精神疾病包括对其他物质成瘾的主要危险因素，与包括大脑中神经元和神经胶质活动紊乱在内的几种神经病理学有关。它影响特定脑区的碳代谢，并扰乱神经元和神经胶质细胞中的神经代谢物稳态。酒精引起的大脑神经化学特征变化伴随着与奖励失调和对戒断的应激反应敏感相关的负面情绪状态。然而，慢性酒精使用后大脑神经胶质活动和神经化学失调的潜在变化仍知之甚少。本研究使用 [1,6-C] 葡萄糖和 [2-C] 醋酸钠分别灌注，在戒断 48 小时后，使用 H-[C]-NMR 光谱评估慢性乙醇使用对区域神经-神经胶质代谢活性的影响。除了以特定于脑区的方式建立神经代谢物的详细 C 标记外，我们的结果还表明，慢性乙醇诱导的认知缺陷伴随着海马体和纹状体中总葡萄糖氧化率的降低。此外，使用 [2-C] 醋酸盐输注，我们显示酒精诱导海马体和前额叶皮层中星形胶质细胞代谢活性增加。有趣的是，海马体和前额叶皮层中星形胶质细胞活性的增加与单羧酸转运蛋白的差异表达有关，这些转运蛋白调节大脑中的醋酸盐摄取和代谢。
