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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 13C NMR.

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 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.

journal_name

J Neurosci Res

journal_title

Journal of neuroscience research

authors

Fonseca CP,Sierra A,Geraldes CF,Cerdán S,Castro MM

doi

10.1002/jnr.21900

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

1046-55

issue

eissn

0360-4012

issn

1097-4547

journal_volume

pub_type

杂志文章

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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 13C NMR.