Stable isotope-resolved metabolomic analysis of lithium effects on glial-neuronal metabolism and interactions.

Metabolomics : Official Journal of the Metabolomic Society
Teresa W-M FanRima Kaddurah-Daouk

Abstract

Despite the long-established therapeutic efficacy of lithium in the treatment of bipolar disorder (BPD), its molecular mechanism of action remains elusive. Newly developed stable isotope-resolved metabolomics (SIRM) is a powerful approach that can be used to elucidate systematically how lithium impacts glial and neuronal metabolic pathways and activities, leading ultimately to deciphering its molecular mechanism of action. The effect of lithium on the metabolism of three different (13)C-labeled precursors ([U-(13)C]-glucose, (13)C-3-lactate or (13)C-2,3-alanine) was analyzed in cultured rat astrocytes and neurons by nuclear magnetic resonance (NMR) spectroscopy and gas chromatography mass spectrometry (GC-MS). Using [U-(13)C]-glucose, lithium was shown to enhance glycolytic activity and part of the Krebs cycle activity in both astrocytes and neurons, particularly the anaplerotic pyruvate carboxylation (PC). The PC pathway was previously thought to be active in astrocytes but absent in neurons. Lithium also stimulated the extracellular release of (13)C labeled-lactate, -alanine (Ala), -citrate, and -glutamine (Gln) by astrocytes. Interrogation of neuronal pathways using (13)C-3-lactate or (13)C-2,3-Ala as tracers indicated a hig...Continue Reading

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Feb 26, 2011·Journal of Biomolecular NMR·Teresa W-M Fan, Andrew N Lane
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Jun 15, 2011·Metabolomics : Official Journal of the Metabolomic Society·Teresa W-M FanJun Yan
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Jun 1, 2012·Metabolomics : Official Journal of the Metabolomic Society·Teresa W-M FanAndrew N Lane
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