Elsevier

Brain Research

Volume 1106, Issue 1, 23 August 2006, Pages 205-210
Brain Research

Short Communication
Preliminary evidence for a link between schizophrenia and NMDA–glycine site receptor ligand metabolic enzymes, d-amino acid oxidase (DAAO) and kynurenine aminotransferase-1 (KAT-1)

https://doi.org/10.1016/j.brainres.2006.05.082Get rights and content

Abstract

Preliminary investigations, studying gene expression and biochemical activities of enzymes d-amino acid oxidase (DAAO) and kynurenine aminotransferase-1 (KAT-1), revealed elevated cerebellar KAT-1 and DAAO activities in post-mortem brain samples from schizophrenic versus normal individuals. In addition, we have identified a transcript of DAAO, which was expressed in significantly higher quantities in the diseased cerebellum but not detected in the parietal cortex where DAAO activity is absent.

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Acknowledgments

This study was supported by grants from the Clive and Vera Ramaciotti and Rebecca Cooper Foundations. Post-mortem tissues were received from the Australian Brain Donor Programs NWS Tissue Resource Centre, which is supported by the National Health and Medical Research Council of Australia.

References (37)

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    In the brain, KYNA is produced by astrocytes and acts as an antagonist at N-Methyl-d-aspartate (NMDA) and α7 nicotinic acetylcholine receptors, providing the biological rationale for using this biomarker for diagnostic purposes and as a target of potential intervention (Bernstein et al., 2009; Schwarcz et al., 2012). Although the exact mechanisms of elevated KYNA levels in schizophrenia remain to be elucidated, both inflammation and genetic variants in the enzymes of the kynurenine pathway (e.g., kynurenine 3-monooxygenase) could be responsible for elevated levels of KYNA (Aoyama et al., 2006; Kapoor et al., 2006; Wonodi et al., 2011; Holtze et al., 2012). Decreased concentrations of a co-agonist of NMDA receptors, d-serine, were detected in the plasma and CSF of patients with schizophrenia.

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Present address: School of Pharmacology and Medicine, University of Western Australia, M510, Perth 6009, Australia.

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