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Protection of the PC12 Cells by Nesfatin-1 Against Methamphetamine-Induced Neurotoxicity

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Abstract

Methamphetamine (METH) abuse causes irreversible neural damages in the brain. It is well-known that Nesfatin-1, a neuropeptide involved in appetite and body weight, has a neuroprotective effect against oxidative stress and apoptotic response in dopaminergic cells. Therefore, the present study aimed to evaluate if Nesfatin-1 could antagonize the neurotoxicity induced by METH in the PC12 cells through suppressing apoptosis, autophagy, and oxidative stress. In this in vitro study, the pretreatment of the PC12 cells was conducted using 1, 5, 10, and 100 ng/ml of Nesfatin-1 for 1 h, followed by exposure to METH (0.5, 1, 2, 3, 4, and 6 mM) for 24 h to determine the appropriate toxic and most protective dose of METH and Nesfatin-1 by MTT assay, respectively. Further investigations were performed to inspect oxidative stress, apoptosis, and autophagy responses. According to the obtained results, Nesfatin-1 could mitigate the overproduction of the reactive oxygen species in the METH-exposed PC12 cells. Moreover, Nesfatin-1 could ameliorate METH-induced apoptotic cell death by augmenting the cell viability and decreasing apoptotic rates. In addition, the amounts of autophagosome formation and microtubule-associated protein-light chain 3 levels were decreased significantly demonstrating the protective effect of Nesfatin-1 against autophagy induced by METH. In conclusion, Nesfatin-1 could be regarded as a therapeutic agent against cell injury triggered by METH by inhibiting oxidative stress, apoptosis, and autophagy.

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Acknowledgements

This study was financially supported by the Research Deputy of Shahroud University of Medical Sciences, Shahroud, Iran (Grant No. 97181).

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Authors and Affiliations

  1. Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran

    Zahra Abbasi & Simin Nazarnezhad

  2. Addiction Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

    Mehdi Khaksari

  3. Department of Medical Biotechnology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran

    Asghar Shayannia & Majid Rahmati

  4. School of Paramedicine, Shahroud University of Medical Sciences, Shahroud, Iran

    Moslem Jafarisani

  5. Cancer Prevention Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

    Ghasem Abbaszadeh-Goudarzi

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  1. Zahra Abbasi
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Contributions

ZA and MR wrote the paper and analyzed the data. ZA and SN performed the experiments. MJ was a scientific advisor. MR, MKH, ASH, and GHA conceived and designed the experiments. All authors read and approved the manuscript and all data were generated in-house and no paper mill was used.

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Correspondence to Majid Rahmati.

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Abbasi, Z., Khaksari, M., Shayannia, A. et al. Protection of the PC12 Cells by Nesfatin-1 Against Methamphetamine-Induced Neurotoxicity. Int J Pept Res Ther 28, 107 (2022). https://doi.org/10.1007/s10989-022-10417-x

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