The relation between peripheral and central glutamate and glutamine in healthy male volunteers

The relation between peripheral and central glutamate and glutamine in healthy male volunteers

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J Psychiatry Neurosci 2006;31(6):406-10

Yanina Shulman, BSc (Hons); Suzanne Grant, PhD; Peter Seres, MScE; Chris Hanstock, PhD; Glen Baker, PhD; Philip Tibbo, MD, FRCPC

Shulman, Baker, Tibbo — Centre for Neuroscience, University of Alberta; Shulman, Grant, Baker, Tibbo — Bebensee Schizophrenia Research Unit and Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Alta; Seres, Hanstock — Department of Biomedical Engineering, University of Alberta, Edmonton, Alta.

Abstract

Objective: High-field strength proton magnetic resonance spectroscopy (1H-MRS) and peripheral blood analyses reported in the literature reveal glutamate (Glu) and glutamine (Gln) abnormalities in schizophrenia. Given the relative ease and feasibility of using peripheral measures, the present study investigates the relation between peripheral and brain Glu and Gln levels.
Methods: We recruited healthy volunteers (n = 17, mean age 21.9 [standard deviation 2.9, range 18–29] yr) between May and December 2005. All participants underwent 3 Tesla 1H-MRS analysis with segmentation (grey matter, white matter, cerebrospinal fluid) at the Nuclear Magnetic Resonance Centre at the University of Alberta Hospital to quantify medial prefrontal cortical (mPFC) Glu and Glx (i.e., combination of Glu and Gln). Within 1 week of 1H-MRS analysis, we collected plasma from the same participants for Glu and Gln quantification, using high-performance liquid chromatography at the Neurochemical Research Unit at the University of Alberta.
Results: There was no correlation between plasma Glu and either medial prefrontal cortical Glu or Glx (R1,15 = 0.019, p = 0.944 and R1,15 = 0.081, p = 0.757, respectively). Similarly, there was no correlation between plasma Gln and either mPFC Glu or Glx (R1,15 = 0.029, p = 0.911 and R1,15 = 0.025, p = 0.925, respectively).
Conclusions: Our findings support the use of 1H-MRS, instead of peripheral blood analysis, for investigating glutamatergic dysfunction in the brain.

Résumé

Objectif : La spectroscopie par résonance magnétique des protons à champ de force puissant (1H-MRS) et les analyses de sang périphérique décrites dans les publications révèlent des anomalies du glutamate (Glu) et de la glutamine (Gln) dans les cas de schizophrénie. Comme il est relativement facile et faisable d’utiliser des mesures du sang périphérique, la présente étude porte sur le lien entre la concentration de Glu et de Gln dans le sang périphérique et dans le cerveau.
Méthodes : Nous avons recruté des volontaires en bonne santé (n = 17, âge médian de 21,9 [écart type de 2,9; plage de 18 à 29] ans) entre mai et décembre 2005. Tous les patients ont subi à une analyze 1H-MRS à 3 Tesla avec segmentation (matière grise, matière blanche, liquide céphalorachidien) au Centre de résonance magnétique nucléaire de l’Hôpital de l’Université de l’Alberta afin de quantifier les concentrations de Glu et de Glx (c.-à-d. combinaison de Glu et de Gln) dans le cortex préfrontal interne (CPFi). Dans la semaine qui a suivi l’analyse 1H-MRS, nous avons prélevé du plasma chez les mêmes participants pour quantifier les concentrations de Glu et de Gln par chromatographie liquide haute performance à l’Unité de recherche neurochimique de l’Université de l’Alberta.
Résultats : Il n’y avait aucune corrélation entre la Glu plasmatique et la concentration de Glu ou de Glx dans le cortex préfrontal interne (R1,15 = 0,019, p = 0,944 et R1,15 = 0,081, p = 0,757 respectivement). De même, il n’y avait aucune corrélation entre la Gln plasmatique et la Glu ou la Glx dans le CPFi (R1,15 = 0,029, p = 0,911 et R1,15 = 0,025, p = 0,925 respectivement).
Conclusion : Nos constatations appuient l’utilisation de la technique 1H-MRS au lieu de l’analyse de sang périphérique pour investiguer une dysfonction glutamatergique dans le cerveau.


Medical subject headings: glutamate; glutamine; magnetic resonance spectroscopy; prefrontal cortex; plasma; schizophrenia.

Competing interests: None declared.

Acknowledgements: This research was supported by the Bebensee Schizophrenia Research Foundation, University of Alberta Hospital Foundation, Canadian Institutes of Health Research, Alberta Heritage Foundation for Medical Research, Canada Research Chairs and Canada Foundation for Innovation programs, and the Natural Sciences and Engineering Research Council of Canada.

Contributors: Drs. Shulman, Baker and Tibbo designed the study. Drs. Shulman, Grant, Seres, Hanstock and Tibbo acquired the data; Drs. Shulman, Grant, Hanstock, Baker and Tibbo analyzed it. Drs. Shulman and Grant wrote the article; Drs. Seres, Hanstock, Baker and Tibbo critically reviewed it. All authors gave final approval for the article to be published.

Submitted Mar. 6, 2006; Revised May 1, 2006; Jul. 6, 2006; Jul. 31, 2006; Accepted Aug. 8, 2006

Correspondence to: Dr. Philip G. Tibbo, Department of Psychiatry, University of Alberta, 1E7.11 WMC, Edmonton AB T6G 2B7; fax 780 407-6672; ptibbo@ualberta.ca