Neuronal metabolomics by ion mobility mass spectrometry: cocaine effects on glucose and selected biogenic amine metaboli
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ORIGINAL PAPER
Neuronal metabolomics by ion mobility mass spectrometry: cocaine effects on glucose and selected biogenic amine metabolites in the frontal cortex, striatum, and thalamus of the rat Kimberly A. Kaplan & Veronica M. Chiu & Peter A. Lukus & Xing Zhang & William F. Siems & James O. Schenk & Herbert H. Hill Jr
Received: 26 October 2012 / Revised: 30 November 2012 / Accepted: 6 December 2012 / Published online: 12 January 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract We report results of studies of global and targeted neuronal metabolomes by ambient pressure ion mobility mass spectrometry. The rat frontal cortex, striatum, and thalamus were sampled from control nontreated rats and those treated with acute cocaine or pargyline. Quantitative evaluations were made by standard additions or isotopic dilution. The mass detection limit was ∼100 pmol varying with the analyte. Targeted metabolites of dopamine, serotonin, and glucose followed the rank order of distribution expected between the anatomical areas. Data was evaluated by principal component analysis on 764 common metabolites (identified by m/z and reduced mobility). Differences between anatomical areas and treatment groups were observed for 53 % of these metabolites using principal component analysis. Global and targeted metabolic differences were observed between the three anatomical areas with contralateral differences between some areas. Following drug treatments, global and targeted metabolomes were found to shift relative to controls and still maintained anatomical differences. Pargyline reduced 3,4-dihydroxyphenylacetic acid below detection limits, and 5-HIAA varied between anatomical regions. Notable findings were: (1) global metabolomes were different between anatomical areas and were altered by acute cocaine providing a broad but targeted window of discovery for metabolic changes produced by drugs of abuse; (2) quantitative analysis was demonstrated using isotope dilution and standard addition; (3) cocaine changed glucose and biogenic amine metabolism in K. A. Kaplan (*) : V. M. Chiu : P. A. Lukus : X. Zhang : W. F. Siems : J. O. Schenk : H. H. Hill Jr Department of Chemistry, Washington State University, Pullman, WA 99164, USA e-mail: [email protected]
the anatomical areas tested; and (4) the largest effect of cocaine was on the glycolysis metabolome in the thalamus confirming inferences from previous positron emission tomography studies using 2-deoxyglucose. Keywords Ion mobility mass spectrometry . Cocaine . Isotope dilution . Glucose . Standard addition
Introduction Metabolomics is often used to describe the “global” analysis of biological matrices for low molecular mass metabolites. From the overall patterns within certain samples, it is possible to distinguish between disease states, strains of animals, detection of pharmacological or toxic effects obtained from the administration of drugs [1]. Metabolomes are unique and dynamic, and are the precursors or end products representing the sum of ongoing biological processes.
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