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Mechanisms underlying Li + effects in glutamatergic and GABAergic neurotransmissions in the adult rat brain and in primary cultures of neural cells as revealed by 13 C NMR
Author(s) -
Fonseca Carla P.,
Sierra Alejandra,
Geraldes Carlos F. G. C.,
Cerdán Sebastion,
Castro M. Margarida C. A.
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21900
Subject(s) - glutamatergic , glutamate receptor , gabaergic , glutamine , metabolism , chemistry , glucose uptake , biochemistry , medicine , carbohydrate metabolism , endocrinology , biology , amino acid , receptor , insulin
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 μmol/min/kg) or (2‐ 13 C) acetate (240 μmol/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 (γ‐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. © 2008 Wiley‐Liss, Inc.