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

This study investigates the effects of ethanol on neuronal and astroglial metabolism using 1 H‐[ 13 C]‐ NMR spectroscopy in conjunction with infusion of [1,6‐ 13 C 2 ]/[1‐ 13 C]glucose or [2‐ 13 C]acetate, respectively. A three‐compartment metabolic model was fitted to the 13 C turnover of Glu C3 , Glu C4 , GABA C 2 , GABA C 3 , Asp C3 , and Gln C4 from [1,6‐ 13 C 2 ]glucose to determine the rates of tricarboxylic acid (TCA) and neurotransmitter cycle associated with glutamatergic and GABA ergic neurons. The ratio of neurotransmitter cycle to TCA cycle fluxes for glutamatergic and GABA egic neurons was obtained from the steady‐state [2‐ 13 C]acetate experiment and used as constraints during the metabolic model fitting. 1 H 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. Gln C4 labeling was found to be unchanged from a 15 min infusion of [2‐ 13 C]acetate suggesting that acute ethanol exposure does not affect astroglial metabolism in naive mice. Rates of TCA and neurotransmitter cycle associated with glutamatergic and GABA ergic 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. image Depletion of ethanol and its effect on brain functions were measured using 1 H and 1 H‐[ 13 C]‐NMR spectroscopy in conjunction with infusion of 13 C‐labeled substrates. Ethanol depletion from brain follows zero order kinetics. Ethanol perturbs level of glutamate, and the excitatory and inhibitory activity in mice brain.