Mechanisms underlying Li+ effects in glutamatergic and GABAergic neurotransmissions in the adult rat brain and in primary cultures of neural cells as revealed by 13C NMR.
We investigated by (13)C nuclear magnetic resonance (NMR) the mechanisms underlying Li(+) effects on glutamatergic and GABAergic neurotransmission systems in the adult rat brain and in primary cultures of cortical neurons and astrocytes during the metabolism of (1-(13)C) glucose or (2-(13)C) acetate. Adult male rats receiving a single dose of Li(+) intraperitoneally (7 mmol/kg) were infused 2 hr later, for 60 min, with (1-(13)C) glucose (80 mumol/min/kg) or (2-(13)C) acetate (240 micromol/min/kg). High-resolution (13)C NMR spectra of brain extracts prepared after the infusion revealed that Li(+) significantly decreased the incorporation of (13)C in glutamate and GABA (gamma-aminobutyric acid) carbons from (1-(13)C) glucose, but not from (2-(13)C) acetate. To complement the in vivo approach, primary cultures of cortical neurons or astrocytes were incubated with 1 mM uniformly (13)C-labeled glucose or 5 mM (2-(13)C) acetate, in the absence and presence of increasing Li(+) concentrations up to 15 mM. Under these conditions, Li(+) significantly decreased neuronal glucose uptake in a concentration-dependent manner without apparent effects on astrocytic acetate uptake. Extracts prepared at the end of the incubations showed that Li(+) significantly decreased the incorporation of (13)C labeling into GABA carbons from its precursor glutamate in neurons, but such a decrease into glutamine carbons in astrocytes was not statistically significant. Our results indicate that the effects of Li(+) are mediated through a reduction of neuronal glucose uptake, resulting in a decrease of glutamatergic and GABAergic neurotransmission without apparent effects on astrocytic metabolism.
Department of Biochemistry and Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Carla P
CP
Fonseca
Alejandra
A
Sierra
Carlos F G C
CF
Geraldes
Sebastion
S
Cerdán
M Margarida C A
MM
Castro
D000085:Acetates / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D002247:Carbon Isotopes; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000085:Acetates; D002247:Carbon Isotopes; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D018021:Lithium Chloride; D005947:Glucose