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Investigation of the protective effect of resveratrol in an MK-801-induced mouse model of schizophrenia

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Abstract

Increasing evidence supports the view that oxidative stress and brain demyelination play an important role in the pathogenesis of schizophrenia. Resveratrol is a powerful antioxidant with neuroprotective effects. This study aimed to assess the effect of resveratrol on schizophrenia-like behaviors and possible brain demyelination induced by MK-801, an N-methyl-D-aspartate glutamate receptor antagonist, and the underlying neuroprotective mechanism. Resveratrol (40 mg/kg/day/, intraperitoneal) was administered to mice for 14 days. MK-801 (1 mg/kg/day, intraperitoneal) was injected into the mice 4 h after the resveratrol administration for 14 days. The open-field and elevated-plus maze tests were performed to detect behavior changes on the 15th day. Following the behavioral tests, the expression of the myelin basic protein (MBP) was measured with the real-time PCR (RT-PCR) method, while total oxidant capacity (TOS) and total antioxidant capacity (TAS), which are the biomarkers of oxidative damage, were measured with the ELISA method. Hematoxylin-eosin staining was also used to identify stereological and pathological changes in the brain. According to the results obtained, this study showed for the first time that resveratrol prevented glial cell infiltration induced in the brain by MK-801 and shrinkage of nerve cell nuclei in the hippocampus and corpus callosum. However, the resveratrol administrations did not correct behavioral disorders and demyelination of schizophrenia. Although resveratrol partially prevented oxidative damage in the brain in the mice that were injected with MK-801, it was determined that this effect was not statistically significant. These results showed that resveratrol administration partially protects tissues against MK-801-induced neurodegeneration, and resveratrol may be used in combination with different antioxidants or at different doses in future studies.

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Data availability

The datasets used/analyzed in this study are available from the corresponding author on reasonable request.

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Funding

This study was financially supported by the Scientific Research Project Coordination Unit at Afyon Kocatepe University (16.Kariyer.130).

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Contributions

The idea of the research was recommended by M.S.A, who also took part in the design of the study. M.S.A. and R.T. performed the experimental work and wrote/drafted/edited the manuscript, and interpreted the results. M.S.A., R.T., and H.H.D. performed the laboratory analyses. All authors were involved in revising the manuscript critically for important intellectual content, and all authors approved the final version to be published.

Corresponding author

Correspondence to Ruhi Türkmen.

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Ethics approval

The Animal Experiments Local Ethics Board, Afyon Kocatepe University, Afyon, (Registration number: AKUHADYEK-132-16) has approved this study.

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The authors declare no competing interests.

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Responsible Editor: Mohamed M. Abdel-Daim

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Akosman, .S., Türkmen, R. & Demirel, H.H. Investigation of the protective effect of resveratrol in an MK-801-induced mouse model of schizophrenia. Environ Sci Pollut Res 28, 65872–65884 (2021). https://doi.org/10.1007/s11356-021-15664-x

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  • DOI: https://doi.org/10.1007/s11356-021-15664-x

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