Cited by 75Schizophrenia research and treatmentAntioxidant Activity and Oxidative StressRedox biology and oxidative stress

Decreased glutathione levels and altered antioxidant defense in an animal model of schizophrenia: Long-term effects of perinatal phencyclidine administration

Radonjić, Nevena V., Knežević, Iva D., Vilimanovich, Urosh, Kravić-Stevović, Tamara, Marina, Ljiljana V., Nikolić, Tatjana, Todorović, Veljko, Bumbaširević, Vladimir +1 more·2010·Neuropharmacology

Abstract

Perinatal phencyclidine (PCP) administration to rodents represents one of the more compelling animal models of schizophrenia. There is evidence that decreased glutathione (GSH) levels and oxidative stress mediated through free radicals in the central nervous system are involved in the pathophysiology of this disease. Limited data are available on the role of free radicals in neurotoxicity induced by NMDA-receptor antagonists. The aim of this study was to elucidate the long-term effects of perinatal phencyclidine administration on superoxide dismutase (SOD), catalase (CAT), gamma-glutamyl cisteine ligase (gamma-GCL), glutathione peroxidase (GPx), glutathione reductase (GR) and levels of lipid peroxides as well as GSH content. The Wistar rats were treated on the 2nd, 6th, 9th and 12th postnatal (PN) days with either phencyclidine (10mg/kg) or saline and sacrificed on PN70. The activities of antioxidant enzymes and level of lipid peroxides and GSH were determined in dorsolateral frontal cortex (dlFC), hippocampus, thalamus and caudate nucleus. Expression of SOD1 and SOD2 was determined by immunoblot. Region-specific changes of the measured parameters were observed. Decreased content of reduced GSH and altered activities of GR, GPx and SOD were determined in dlFC. In hippocampus, reduced GSH content and decreased activities of GPx and GR were accompanied with increased activity of gamma-GCL and increased level of lipid peroxides. gamma-GCL and GSH content were also decreased in caudate nucleus, while in thalamus major findings are increased levels of lipid peroxides and GR activity and decreased gamma-GCL activity. It can be concluded that perinatal PCP administration produces long-term alteration of antioxidant defense. Further studies are necessary in order to clarify role of redox dysregulation in the pathogenetic mechanism of schizophrenia.

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Crossref · 10.1016/j.neuropharm.2009.12.009

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  • Synaptic NMDAR activity enhances the capacity of both the glutathione system and the thioredoxin/peroxiredoxin system through the transcriptional control of several key antioxidant genes.

    “At the cellular level, synaptic NMDAR activity enhances the capacity of both the glutathione system and thioredoxin/peroxiredoxin system (another important antioxidant pathway in the brain 75 ) through the transcriptional control of several key antioxidant genes 73,76,77 (Figure.4).”

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Authors
Radonjić, N. V., Knežević, I. D., Vilimanovich, U., Kravić-Stevović, T., Marina, L. V., Nikolić, T., Todorović, V., Bumbaširević, V., & Petronijević, N. D.
Affiliations
  • University of Belgrade (RS)
  • Univerzitetski Klinički Centar Srbije (RS)
  • Military Medical Academy (RS)
Corresponding author
Petronijević, Nataša D.
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2010-03
Volume
58
Issue
4-5
Pages
739-745
ISSN
0028-3908 (ISSN-L)
OpenAlex
W2074096568
Cited by
75
References
68
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 8 · 2016: 6 · 2015: 6 · 2014: 1 · 2013: 8 · 2012: 7
FWCI
3.92
Type
journal article
Language
en
Open access
closed
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
schizophrenia, phencyclidine, glutathione, antioxidant defense, oxidative stress, lipid peroxidation, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, gamma-glutamylcysteine synthetase, redox dysregulation, dorsolateral prefrontal cortex, hippocampus, caudate nucleus, thalamus, long-term neurotoxicity
MeSH terms
Animals, Animals, Newborn, Antioxidants, Brain, Disease Models, Animal, Female, Free Radicals, Glutathione, Phencyclidine, Pregnancy, Schizophrenia, Time Factors, Rats, Wistar, Rats

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