| Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. | |
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MedLine Citation:
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PMID: 21036897 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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The levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the branched kynurenine pathway (KP) of tryptophan degradation and antagonist of α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors, are elevated in the prefrontal cortex (PFC) of individuals with schizophrenia (SZ). Because endogenous KYNA modulates extracellular glutamate and acetylcholine levels in the PFC, these increases may be pathophysiologically significant. Using brain tissue from SZ patients and matched controls, we now measured the activity of several KP enzymes (kynurenine 3-monooxygenase [KMO], kynureninase, 3-hydroxyanthranilic acid dioxygenase [3-HAO], quinolinic acid phosphoribosyltransferase [QPRT], and kynurenine aminotransferase II [KAT II]) in the PFC, ie, Brodmann areas (BA) 9 and 10. Compared with controls, the activities of KMO (in BA 9 and 10) and 3-HAO (in BA 9) were significantly reduced in SZ, though there were no significant differences between patients and controls in kynureninase, QPRT, and KAT II. In the same samples, we also confirmed the increase in the tissue levels of KYNA in SZ. As examined in rats treated chronically with the antipsychotic drug risperidone, the observed biochemical changes were not secondary to medication. A persistent reduction in KMO activity may have a particular bearing on pathology because it may signify a shift of KP metabolism toward enhanced KYNA synthesis. The present results further support the hypothesis that the normalization of cortical KP metabolism may constitute an effective new treatment strategy in SZ. |
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Authors:
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Korrapati V Sathyasaikumar; Erin K Stachowski; Ikwunga Wonodi; Rosalinda C Roberts; Arash Rassoulpour; Robert P McMahon; Robert Schwarcz |
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Publication Detail:
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Type: Journal Article Date: 2010-10-29 |
Journal Detail:
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Title: Schizophrenia bulletin Volume: 37 ISSN: 1745-1701 ISO Abbreviation: Schizophr Bull Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-10-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0236760 Medline TA: Schizophr Bull Country: United States |
Other Details:
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Languages: eng Pagination: 1147-56 Citation Subset: IM |
Affiliation:
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*To whom correspondence should be addressed; Maryland Psychiatric Research Center, PO Box 21247, Baltimore, MD 21228; tel: 410-402-7635, fax: 410-747-2434, e-mail: rschwarc@mprc.umaryland.edu. |
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