Differential effects of ethanol on regional glutamatergic and GABAergic neurotransmitter pathways in mouse brain

• Published in: Journal of neurochemistry Vol. 128; no. 5; pp. 628 - 640
• Main Authors: Tiwari, Vivek, Veeraiah, Pandichelvam, Subramaniam, Vaidyanathan, Patel, Anant Bahadur
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.03.2014
• Subjects: 1H MRS; Acetates - metabolism; Algorithms; Amino Acids - metabolism; Animals; Astrocytes - drug effects; Astrocytes - metabolism; Brain; Brain Chemistry - drug effects; Central Nervous System Depressants - pharmacokinetics; Central Nervous System Depressants - pharmacology; Cerebellum - drug effects; Cerebellum - metabolism; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; cerebral metabolism; Ethanol; Ethanol - pharmacokinetics; Ethanol - pharmacology; GABA; gamma-Aminobutyric Acid - physiology; Glucose - metabolism; glutamate; Glutamic Acid - physiology; Kinetics; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred C57BL; Neurons - drug effects; Neurons - metabolism; neurotransmission; Neurotransmitter Agents - physiology; Neurotransmitters; Rodents; Signal Transduction - drug effects; Synaptic Transmission - drug effects; GABA; neurotransmission; ethanol; 1H MRS; glutamate; cerebral metabolism
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.12508

This study investigates the effects of ethanol on neuronal and astroglial metabolism using 1H‐[13C]‐NMR spectroscopy in conjunction with infusion of [1,6‐13C2]/[1‐13C]glucose or [2‐13C]acetate, respectively. A three‐compartment metabolic model was fitted to the 13C turnover of GluC3, GluC4, GABAC2, GABAC3, AspC3, and GlnC4 from [1,6‐13C2]glucose to determine the rates of tricarboxylic acid (TCA) and neurotransmitter cycle associated with glutamatergic and GABAergic neurons. The ratio of neurotransmitter cycle to TCA cycle fluxes for glutamatergic and GABAegic neurons was obtained from the steady‐state [2‐13C]acetate experiment and used as constraints during the metabolic model fitting. 1H MRS measurement suggests that depletion of ethanol from cerebral cortex follows zero order kinetics with rate 0.18 ± 0.04 μmol/g/min. Acute exposure of ethanol reduces the level of glutamate and aspartate in cortical region. GlnC4 labeling was found to be unchanged from a 15 min infusion of [2‐13C]acetate suggesting that acute ethanol exposure does not affect astroglial metabolism in naive mice. Rates of TCA and neurotransmitter cycle associated with glutamatergic and GABAergic neurons were found to be significantly reduced in cortical and subcortical regions. Acute exposure of ethanol perturbs the level of neurometabolites and decreases the excitatory and inhibitory activity differentially across the regions of brain. Depletion of ethanol and its effect on brain functions were measured using 1H and 1H‐[13C]‐NMR spectroscopy in conjunction with infusion of 13C‐labeled substrates. Ethanol depletion from brain follows zero order kinetics. Ethanol perturbs level of glutamate, and the excitatory and inhibitory activity in mice brain. Depletion of ethanol and its effect on brain functions were measured using 1H and 1H‐[13C]‐NMR spectroscopy in conjunction with infusion of 13C‐labeled substrates. Ethanol depletion from brain follows zero order kinetics. Ethanol perturbs level of glutamate, and the excitatory and inhibitory activity in mice brain.