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The protective effect of N-acetylcysteine against MK-801-induced neurodegeneration in mice

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Abstract

Background

Neurological disorders result in not only a decline in the quality of life of patients but also a global economic burden. Therefore, protective medicine becomes more important for society. MK-801 is a chemical agent used to understand the etiology of behavioral disorders and brain degeneration in animal models. This study aims to determine whether N-acetylcysteine (NAC) is useful to treat brain degeneration caused by MK-801, an N-methyl-D-aspartate glutamate receptor antagonist.

Methods and results

Four groups were formed by dividing 24 male BALB/c mice into groups of six. The control group was given a saline solution (10 ml/kg-i.p.). MK-801 (1 mg/kg-i.p.) was given alone to one group, and it was given with NAC (100 mg/kg-i.p.) to another group, while the last group was given only NAC (100 mg/kg-i.p.). The administration of drugs lasted for fourteen days. After the behavioral tests (open field and elevated plus-maze), all animals were euthanised, and brain tissues were collected for real-time PCR, TAS-TOS analysis, hematoxylin-eosin, Kluver-Barrera, and TUNEL staining. In the MK-801 group, besides nuclear shrinkage in neurons, glial cell infiltration, vacuolization in cortical neurons, white matter damage, and apoptosis were observed.

Conclusion

In the mice given NAC as a protective agent, it was observed that behavioral problems improved, antioxidant levels increased, and nuclear shrinkage, glial cell infiltration, vacuolization in neurons, and white matter degeneration were prevented. Moreover, MBP expression increased, and the number of TUNEL-positive cells significantly decreased. As a result, it was observed that NAC may have a protective effect against brain degeneration.

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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 (17.Kariyer.45).

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Authors and Affiliations

  1. Department of Anatomy, Faculty of Veterinary Medicine, Afyon Kocatepe University, Afyon, 03200, Turkey

    Murat Sırrı Akosman

  2. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Afyon Kocatepe University, Afyon, 03200, Turkey

    Ruhi Türkmen

  3. Bayat Vocational School, Afyon Kocatepe University, Afyon, 03200, Turkey

    Hasan Hüseyin Demirel

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  1. Murat Sırrı Akosman
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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.

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Correspondence to Murat Sırrı Akosman.

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The Animal Experiments Local Ethics Board, Afyon Kocatepe University, Afyon (Registration number: AKUHADYEK-189-17) has approved this study.

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Sırrı Akosman, M., Türkmen, R. & Demirel, H.H. The protective effect of N-acetylcysteine against MK-801-induced neurodegeneration in mice. Mol Biol Rep 50, 10287–10299 (2023). https://doi.org/10.1007/s11033-023-08881-9

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