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
✍ Scribed by Carla P. Fonseca; Alejandra Sierra; Carlos F. G. C. Geraldes; Sebastion Cerdán; M. Margarida C. A. Castro
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 228 KB
- Volume
- 87
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
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.