title: Differential effects of ethanol on regional glutamatergic and GABAergic neurotransmitter pathways in mouse brain.
abstract: 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)C2]/[1-(13)C]glucose or [2-(13)C]acetate, respectively. A three-compartment metabolic model was fitted to the (13)C turnover of GluC3 , GluC4, GABAC 2, GABAC 3, AspC3 , and GlnC4 from [1,6-(13)C2 ]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-(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. GlnC4 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 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 (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.
authors.affiliation: NMR Microimaging and Spectroscopy, CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Tiwari
authors.forename: Pandichelvam
authors.initials: P
authors.lastname: Veeraiah
authors.forename: Vaidyanathan
authors.initials: V
authors.lastname: Subramaniam
authors.forename: Anant Bahadur
authors.initials: AB
authors.lastname: Patel
mesh_terms: D000085:Acetates / Q000378:metabolism; D000465:Algorithms; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000502:physiology*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000085:Acetates; D000596:Amino Acids; D002492:Central Nervous System Depressants; D018377:Neurotransmitter Agents; D000431:Ethanol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005947:Glucose
keywords: 1H MRS; GABA; cerebral metabolism; ethanol; glutamate; neurotransmission