title: Altered brain arginine metabolism in schizophrenia.
abstract: Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease.
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand.|Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: P
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand.|Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Y
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand.|Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: N D
authors.initials: ND
authors.lastname: Collie
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute for Neuroscience and Mental Health, Parkville, VIC, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Dean
authors.affiliation: Brain Health Research Centre, University of Otago, Dunedin, New Zealand.|Department of Psychology, University of Otago, Dunedin, New Zealand.
authors.forename: D K
authors.initials: DK
authors.lastname: Bilkey
authors.affiliation: Brain Health Research Centre, University of Otago, Dunedin, New Zealand.|School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000376:Agmatine / Q000378:metabolism; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D001344:Autopsy; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D002956:Citrulline / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009952:Ornithine / Q000378:metabolism; D012044:Regression Analysis; D012559:Schizophrenia / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002956:Citrulline; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000376:Agmatine; D001120:Arginine; D009952:Ornithine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C477631:ARG2 protein, human; D001119:Arginase