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      Effects of Nostoc commune extract on the cerebral oxidative and neuroinflammatory status in a mice model of schizophrenia

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          Abstract

          Cyanobacterium Nostoc commune has long been used to alleviate various diseases. This research examines the effects of Nostoc commune extract (NCE) against behavioral disorders, cerebral oxidative stress, and inflammatory damage in the ketamine-induced schizophrenia model. Oral NCE administration (70 and 150 mg/kg/d) is performed after intraperitoneal ketamine injection (20 mg/kg) for 14 consecutive days. The forced swimming and open field tests are used to assess schizophrenia-like behaviors. After the behavioral test, dopamine (DA) level, oxidative stress markers, as well as the interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expression are measured in the cerebral cortex. The results show that NCE treatment ameliorates KET-induced anxiety and depressive-like behaviors in OFT and FST, respectively. NCE considerably decreases the malondialdehyde (MDA) and DA levels and IL-6 and TNF-α expressions in mice with schizophrenia-like symptoms. Also, a significant increase is observed in the glutathione (GSH) level and catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GRx) activity in cerebral tissue. The present study shows that NCE treatment effectively improves KET-induced schizophrenia-like behaviors and oxidative and inflammatory damage. Therefore, NCE, via its bioactive constituents, could have strong neuroprotective effects in the schizophrenia-like model.

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          Highlights

          • Nostoc commune extract improve neuroinflammation in SCZ-like mice.

          • Nostoc commune extract attenuates depressive and anxiety-like behavior.

          • Nostoc commune extract is useful for oxidative stress injury in SCZ-like mice.

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          Most cited references59

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          A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding

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            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.
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              Dopamine and glutamate in schizophrenia: biology, symptoms and treatment

              Glutamate and dopamine systems play distinct roles in terms of neuronal signalling, yet both have been proposed to contribute significantly to the pathophysiology of schizophrenia. In this paper we assess research that has implicated both systems in the aetiology of this disorder. We examine evidence from post‐mortem, preclinical, pharmacological and in vivo neuroimaging studies. Pharmacological and preclinical studies implicate both systems, and in vivo imaging of the dopamine system has consistently identified elevated striatal dopamine synthesis and release capacity in schizophrenia. Imaging of the glutamate system and other aspects of research on the dopamine system have produced less consistent findings, potentially due to methodological limitations and the heterogeneity of the disorder. Converging evidence indicates that genetic and environmental risk factors for schizophrenia underlie disruption of glutamatergic and dopaminergic function. However, while genetic influences may directly underlie glutamatergic dysfunction, few genetic risk variants directly implicate the dopamine system, indicating that aberrant dopamine signalling is likely to be predominantly due to other factors. We discuss the neural circuits through which the two systems interact, and how their disruption may cause psychotic symptoms. We also discuss mechanisms through which existing treatments operate, and how recent research has highlighted opportunities for the development of novel pharmacological therapies. Finally, we consider outstanding questions for the field, including what remains unknown regarding the nature of glutamate and dopamine function in schizophrenia, and what needs to be achieved to make progress in developing new treatments.
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                Author and article information

                Contributors
                Journal
                Biochem Biophys Rep
                Biochem Biophys Rep
                Biochemistry and Biophysics Reports
                Elsevier
                2405-5808
                07 December 2023
                March 2024
                07 December 2023
                : 37
                : 101594
                Affiliations
                [a ]Department of Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran
                [b ]Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran
                [c ]Department of Plant Sciences, University of Mazandaran, Babolsar, Iran
                Author notes
                []Corresponding author. Department of Animal Sciences, University of Mazandaran, Babolsar, Iran. a.hajizadeh@ 123456umz.ac.ir
                Article
                S2405-5808(23)00175-9 101594
                10.1016/j.bbrep.2023.101594
                10873873
                38371525
                00ffc816-fe94-4cc0-bad2-ef12ffa6cabb
                © 2023 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 August 2023
                : 19 November 2023
                : 22 November 2023
                Categories
                Research Article

                nostoc commune,ketamine,schizophrenia,oxidative damages,inflammatory cytokines,mice

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