4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Influence of Cyclooxygenase-2 Inhibitors on Kynurenic Acid Production in Rat Brain in Vitro

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Significant body of evidence suggests that abnormal kynurenic acid (KYNA) level is involved in the pathophysiology of central nervous system disorders. In the brain, KYNA is synthesized from kynurenine (KYN) by kynurenine aminotransferases (KATs), predominantly by KAT II isoenzyme. Blockage of ionotropic glutamate (GLU) receptors is a main cellular effect of KYNA. High KYNA levels have been linked with psychotic symptoms and cognitive dysfunction in animals and humans. As immunological imbalance and impaired glutamatergic neurotransmission are one of the crucial processes in neurological pathologies, we aimed to analyze the effect of anti-inflammatory agents, inhibitors of cyclooxygenase-2 (COX-2): celecoxib, niflumic acid, and parecoxib, on KYNA synthesis and KAT II activity in rat brain in vitro. The influence of COX-2 inhibitors was examined in rat brain cortical slices and on isolated KAT II enzyme. Niflumic acid and parecoxib decreased in a dose-dependent manner KYNA production and KAT II activity in rat brain cortex in vitro, whereas celecoxib was ineffective. Molecular docking results suggested that niflumic acid and parecoxib interact with an active site of KAT II. In conclusion, niflumic acid and parecoxib are dual COX-2 and KAT II inhibitors.

          Electronic supplementary material

          The online version of this article (10.1007/s12640-018-9952-9) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references69

          • Record: found
          • Abstract: found
          • Article: not found

          Inflammation in Schizophrenia: Pathogenetic Aspects and Therapeutic Considerations

          This paper discusses the current evidence from animal and human studies for a central role of inflammation in schizophrenia. In animal models, pre- or perinatal elicitation of the immune response may increase immune reactivity throughout life, and similar findings have been described in humans. Levels of pro-inflammatory markers, such as cytokines, have been found to be increased in the blood and cerebrospinal fluid of patients with schizophrenia. Numerous epidemiological and clinical studies have provided evidence that various infectious agents are risk factors for schizophrenia and other psychoses. For example, a large-scale epidemiological study performed in Denmark clearly showed that severe infections and autoimmune disorders are such risk factors. The vulnerability-stress-inflammation model may help to explain the role of inflammation in schizophrenia because stress can increase pro-inflammatory cytokines and may even contribute to a chronic pro-inflammatory state. Schizophrenia is characterized by risk genes that promote inflammation and by environmental stress factors and alterations of the immune system. Typical alterations of dopaminergic, serotonergic, noradrenergic, and glutamatergic neurotransmission described in schizophrenia have also been found in low-level neuroinflammation and consequently may be key factors in the generation of schizophrenia symptoms. Further support for the relevance of a low-level neuroinflammatory process in schizophrenia is provided by the loss of central nervous system volume and microglial activation demonstrated in neuroimaging studies. Last but not least, the benefit of anti-inflammatory medications found in some studies and the intrinsic anti-inflammatory and immunomodulatory effects of antipsychotics provide further support for the role of inflammation in this debilitating disease.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids.

            Prostaglandins play important and diverse roles in the CNS. The first step in prostaglandin synthesis involves enzymatic oxidation of arachidonic acid, which is catalyzed by prostaglandin H(PGH) synthase, also referred to as cyclooxygenase. We have cloned an inducible form of this enzyme from rat brain that is nearly identical to a murine, mitogen-inducible cyclooxygenase identified from fibroblasts. Our studies indicate that this gene, here termed COX-2, is expressed throughout the forebrain in discrete populations of neurons and is enriched in the cortex and hippocampus. Neuronal expression is rapidly and transiently induced by seizures or NMDA-dependent synaptic activity. No expression is detected in glia or vascular endothelial cells. Basal expression of COX-2 appears to be regulated by natural synaptic activity in the developing and adult brain. Both basal and induced expression of COX-2 are inhibited by glucocorticoids, consistent with COX-2 regulation in peripheral tissues. Our studies indicate that COX-2 expression may be important in regulating prostaglandin signaling in brain. The marked inducibility in neurons by synaptic stimuli suggests a role in activity-dependent plasticity.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Meta-analysis of Cerebrospinal Fluid Cytokine and Tryptophan Catabolite Alterations in Psychiatric Patients: Comparisons Between Schizophrenia, Bipolar Disorder, and Depression.

              Schizophrenia, bipolar disorder, and major depressive disorder (MDD) have all been associated with immune system dysfunction, including aberrant cerebrospinal fluid (CSF) levels of cytokines and tryptophan catabolites; however, the pattern of alterations has not been compared across disorders. We performed a meta-analysis of CSF cytokine and tryptophan catabolites in patients with these major psychiatric disorders.
                Bookmark

                Author and article information

                Contributors
                +48 81448 6453 , izabela.zakrocka@umlub.pl
                Journal
                Neurotox Res
                Neurotox Res
                Neurotoxicity Research
                Springer US (New York )
                1029-8428
                1476-3524
                3 September 2018
                3 September 2018
                2019
                : 35
                : 1
                : 244-254
                Affiliations
                [1 ]ISNI 0000 0001 1033 7158, GRID grid.411484.c, Department of Experimental and Clinical Pharmacology, , Medical University of Lublin, ; Jaczewskiego 8b, 20-090 Lublin, Poland
                [2 ]ISNI 0000 0001 1033 7158, GRID grid.411484.c, Department of Biopharmacy, , Medical University of Lublin, ; Chodźki 4a, 20-093 Lublin, Poland
                Author information
                http://orcid.org/0000-0001-5251-7763
                Article
                9952
                10.1007/s12640-018-9952-9
                6313367
                30178287
                3288686f-f558-4dfa-84d0-5d1eae5bf277
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 4 April 2018
                : 9 August 2018
                : 22 August 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004569, Ministerstwo Nauki i Szkolnictwa Wyższego;
                Award ID: DS 448/17
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2019

                Neurosciences
                kynurenic acid,central nervous system,cyclooxygenase-2,cyclooxygenase-2 inhibitors,inflammation

                Comments

                Comment on this article