Abstract
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 1H-[13C]-NMR spectroscopy in conjunction with infusion of [1,6-13C2]glucose and sodium [2-13C]acetate, respectively, after 48 h of abstinence. Besides establishing detailed 13C 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 [2-13C]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.
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Abbreviations
- Ala:
-
Alanine
- AlaC3 :
-
[3-13C]alanine
- Asp:
-
Aspartate
- AspC3 :
-
[3-13C]aspartate
- Cho:
-
Choline
- Cre:
-
Creatine
- CMRAce(Ox) :
-
Cerebral metabolic rate of acetate oxidation
- CMRGlc(Ox) :
-
Cerebral metabolic rate of glucose oxidation
- GABA:
-
γ-Aminobutyric acid
- GABAC2 :
-
[2-13C]GABA
- GABAC4 :
-
[4-13C]GABA
- Gln:
-
Glutamine
- GlnC4 :
-
[4-13C]Glutamine
- Glu:
-
Glutamate
- GluC3 :
-
[3-13C]Glutamate
- GluC4 :
-
[4-13C]Glutamate
- GPC:
-
Glycerophosphocholine
- LacC3 :
-
[3-13C]Lactate
- m-Ino:
-
myo-Inositol
- NAA:
-
N-Acetylaspartate
- NMR:
-
Nuclear magnetic resonance
- Tau:
-
Taurine
- TSP:
-
3-Trimethylsilyl[2,2,3,3-D4]-propionate
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Acknowledgements
This research was supported by the Department of Biotechnology, India [BT/PR27426/MED/122/140/2018 to AK]. UAB acknowledge Council of Scientific and Industrial Research (CSIR), India and department of Biotechnology, India for fellowship. Dr. Robin de Graff of Yale University for providing the POCE pulse sequence. Mr. Jedy Jose, CCMB, Animal House, is duly acknowledged for his constant support in maintaining the quality of animals used for the study.
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This study was supported by Department of Biotechnology grant no: BT/PR27426/MED/122/140/2018.
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UAB, ABP and AK designed the experiments. UAB, SAK, SC performed the experiments, UAB, ABP, AK analyzed the data. UAB, ABP, AK wrote the manuscript. ABP and AK managed the resources and supervised whole project.
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All experimental procedures involving mice were approved by the Institutional Animal Ethics Committee (IAEC) of CSIR-CCMB, Hyderabad, and conducted in accordance with the guidelines established by the Committee for the Purpose of Control and Supervision of Experiments on Animals, Ministry of Environment and Forests, Government of India.
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Bhat, U.A., Kumar, S.A., Chakravarty, S. et al. Differential Effects of Chronic Ethanol Use on Mouse Neuronal and Astroglial Metabolic Activity. Neurochem Res 48, 2580–2594 (2023). https://doi.org/10.1007/s11064-023-03922-y
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DOI: https://doi.org/10.1007/s11064-023-03922-y