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 13C 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 (1-13C) glucose or (2-13C) acetate. Adult male rats receiving a single dose of Li+ intraperitoneally (7 mmol/kg) were infused 2 hr later, for 60 min, with (1-13C) glucose (80 μmol/min/kg) or (2-13C) acetate (240 μmol/min/ kg). High-resolution 13C NMR spectra of brain extracts prepared after the infusion revealed that Li+ significantly decreased the incorporation of 13C in glutamate and GABA (γ-aminobutyric acid) carbons from (1-13C) glucose, but not from (2-13C) acetate. To complement the in vivo approach, primary cultures of cortical neurons or astrocytes were incubated with 1 mM uniformly 13C-labeled glucose or 5 mM (2-13C) acetate, in the absence and presence of increasing Li+ concentrations up to 15 mM. Under these conditions, Li1 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 13C 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.Funded by: Fundação para a Ciência e a Tecnologia (F.C.T.), Portugal and FEDER. Grant Numbers: POCTI/1999/BCI/36160, PRAXIS XXI/BD/21462/99; Spanish Ministry of Education and Science. Grant Numbers: SAF 2001-2245, SAF 2004-03197; Institute of Health Carlos III. Grant Numbers: FISss C03/08, C03/155, C03/10, PI051530, PI051845 and Community of Madrid, Spain.Peer Reviewe