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Protective effects of Nesfatin-1 peptide on cerebral ischemia reperfusion injury via inhibition of neuronal cell death and enhancement of antioxidant defenses

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Abstract

Nesfatin-1 is a novel peptide with anorexigenic and anti-hyperglycemic properties. According to previous studies, this multi-functional peptide protects dopaminergic cells against neurotoxicity via anti-apoptotic effects. In addition, Nesfatin-1 protects myocardial tissue after myocardial infarction via anti-inflammatory and anti-apoptotic mechanisms. In this study, we investigated the neuroprotective effects of nesfatin-1 against cerebral ischemia reperfusion injury in the CA1 area of hippocampus in rats. 56 male Wistar rats (240-270 g) were randomly selected and allocated into four groups: (1) sham, (2) nesfatin-1, (3) ischemia/reperfusion, (4) ischemia/reperfusion+nesfatin-1. Cerebral ischemia induced by the occlusion of the common carotid arteries for 20 min was followed by reperfusion. Saline as a vehicle and nesfatin-1 (20 μg/kg) were injected intraperitoneally (IP) at the start of cerebral reperfusion. Apoptotic and necrotic cell death was detected by TUNEL and Nissl staining. Malondialdehyde (MDA) and antioxidant enzymes (GSH and SOD) levels were measured by the ELISA method. The results showed that cerebral ischemia increased the apoptotic and necrotic cell death in the CA1 area of hippocampus, while, treatment with nesfatin-1significantly reduced apoptotic and necrotic cell death. Moreover, the MDA levels of the hippocampus in ischemic rats were higher, whereas in nesfatin-1-treated rats the MDA levels were decreased. Furthermore, the SOD and GSH levels in the ischemic rats were decreased, whilst in ischemic rats treated with nesfatin-1, the SOD and GSH levels were increased. This study for the first time found that nesfatin-1 treatment improves CA1 hippocampus injuries after cerebral ischemia through preventing neuronal cell death and enhancement of antioxidant defenses.

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References

  • Aboutaleb N, Shamsaei N, Khaksari M, Erfani S, Rajabi H, Nikbakht F (2015) Pre-ischemic exercise reduces apoptosis in hippocampal CA3 cells after cerebral ischemia by modulation of the Bax/Bcl-2 proteins ratio and prevention of caspase-3 activation. J Physiol Sci 65:435–443

    Article  CAS  Google Scholar 

  • Aboutaleb N, Shamsaei N, Rajabi H, Khaksari M, Erfani S, Nikbakht F, Motamedi P, Shahbazi A (2016) Protection of hippocampal CA1 neurons against ischemia/reperfusion injury by exercise preconditioning via modulation of Bax/Bcl-2 ratio and prevention of caspase-3 activation. Basic and clinical neuroscience 7:21

    CAS  PubMed  PubMed Central  Google Scholar 

  • Arvin B, Neville LF, Barone FC, Feuerstein GZ (1996) The role of inflammation and cytokines in brain injury. Neurosci Biobehav Rev 20:445–452

    Article  CAS  Google Scholar 

  • Chen S-D, Yang D-I, Lin T-K, Shaw F-Z, Liou C-W, Chuang Y-C (2011) Roles of oxidative stress, apoptosis, PGC-1α and mitochondrial biogenesis in cerebral ischemia. Int J Mol Sci 12:7199–7215

    Article  CAS  Google Scholar 

  • Chen Y-F, Wu K-J, Huang W-S, Hsieh Y-W, Wang Y-W, Tsai H-Y, Lee M-M (2016) Neuroprotection of Gueichih-Fuling-wan on cerebral ischemia/reperfusion injury in streptozotocin-induced hyperglycemic rats via the inhibition of the cellular apoptosis pathway and neuroinflammation. BioMedicine 6:21

    Article  CAS  Google Scholar 

  • Coimbra-Costa D, Alva N, Duran M, Carbonell T, Rama R (2017) Oxidative stress and apoptosis after acute respiratory hypoxia and reoxygenation in rat brain. Redox Biol 12:216–225

    Article  CAS  Google Scholar 

  • Doyle KP, Simon RP, Stenzel-Poore MP (2008) Mechanisms of ischemic brain damage. Neuropharmacology 55:310–318

    Article  CAS  Google Scholar 

  • Erfani S, Aboutaleb N, Oryan S, Shamsaei N, Khaksari M, Kalalian-Moghaddam H, Nikbakht F (2015a) Visfatin inhibits apoptosis and necrosis of hippocampus CA3 cells following transient global ischemia/reperfusion in rats. Int J Pept Res Ther 21:223–228

    Article  CAS  Google Scholar 

  • Erfani S, Khaksari M, Oryan S, Shamsaei N, Aboutaleb N, Nikbakht F, Jamali-Raeufy N, Gorjipour F (2015b) Visfatin reduces hippocampal CA1 cells death and improves learning and memory deficits after transient global ischemia/reperfusion. Neuropeptides 49:63–68

    Article  CAS  Google Scholar 

  • Foo K, Brismar H, Broberger C (2008) Distribution and neuropeptide coexistence of nucleobindin-2 mRNA/nesfatin-like immunoreactivity in the rat CNS. Neuroscience 156:563–579

    Article  CAS  Google Scholar 

  • Granger DN, Kvietys PR (2015) Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol 6:524–551

    Article  CAS  Google Scholar 

  • Hetman M, Gozdz A (2004) Role of extracellular signal regulated kinases 1 and 2 in neuronal survival. FEBS J 271:2050–2055

    CAS  Google Scholar 

  • Hu G-Q, Du X, Li Y-J, Gao X-Q, Chen B-Q, Yu L (2017) Inhibition of cerebral ischemia/reperfusion injury-induced apoptosis: nicotiflorin and JAK2/STAT3 pathway. Neural Regen Res 12:96–102

    Article  Google Scholar 

  • Jiang G, Wang M, Wang L, Chen H, Chen Z, Guo J, Weng X, Liu X (2015) The protective effect of nesfatin-1 against renal ischemia–reperfusion injury in rats. Ren Fail 37:882–889

    Article  CAS  Google Scholar 

  • Khaksari M, Mehrjerdi FZ, Rezvani ME, Safari F, Mirgalili A, Niknazar S (2017) The role of erythropoietin in remote renal preconditioning on hippocampus ischemia/reperfusion injury. J Physiol Sci 67:163–171

    Article  CAS  Google Scholar 

  • Kowaltowski AJ, Castilho RF, Vercesi AE (2001) Mitochondrial permeability transition and oxidative stress. FEBS Lett 495:12–15

    Article  CAS  Google Scholar 

  • Li Z, Gao L, Tang H, Yin Y, Xiang X, Li Y, Zhao J, Mulholland M, Zhang W (2013) Peripheral effects of nesfatin-1 on glucose homeostasis. PLoS One 8:e71513

    Article  CAS  Google Scholar 

  • Northington FJ, Chavez-Valdez R, Martin LJ (2011) Neuronal cell death in neonatal hypoxia-ischemia. Ann Neurol 69:743–758

    Article  CAS  Google Scholar 

  • Oh S, Shimizu H, Satoh T, Okada S, Adachi S, Inoue K, Eguchi H, Yamamoto M, Imaki T, Hashimoto K (2006) Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature 443:709–712

    Article  Google Scholar 

  • ÖzsavcÍ D, Erşahin M, Şener A, Özakpinar ÖB, Toklu HZ, Akakín D, Şener G, Yeğen BÇ (2011) The novel function of Nesfatin-1 as an anti-inflammatory and Antiapoptotic peptide in subarachnoid hemorrhage–induced oxidative brain damage in rats. Neurosurgery 68:1699–1708

    Article  Google Scholar 

  • Price TO, Samson WK, Niehoff ML, Banks WA (2007) Permeability of the blood–brain barrier to a novel satiety molecule nesfatin-1. Peptides 28:2372–2381

    Article  CAS  Google Scholar 

  • Shamsaei N, Khaksari M, Erfani S, Rajabi H, Aboutaleb N (2015) Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia. Neural Regen Res 10:1245

    Article  Google Scholar 

  • Shen X-L, Song N, Du X-X, Li Y, Xie J-X, Jiang H (2017) Nesfatin-1 protects dopaminergic neurons against MPP+/MPTP-induced neurotoxicity through the C-Raf–ERK1/2-dependent anti-apoptotic pathway. Sci Rep 7

  • Solmaz A, Bahadir E, Gülçiçek OB, Yiğitbaş H, Çelik A, Karagöz A, Özsavcı D, Şirvancı S, Yeğen BÇ (2016) Nesfatin-1 improves oxidative skin injury in normoglycemic or hyperglycemic rats. Peptides 78:1–10

    Article  CAS  Google Scholar 

  • Su Y, Zhang J, Tang Y, Bi F, Liu J-N (2010) The novel function of nesfatin-1: anti-hyperglycemia. Biochem Biophys Res Commun 391:1039–1042

    Article  CAS  Google Scholar 

  • Tan Z, Xu H, Shen X, Jiang H (2015) Nesfatin-1 antagonized rotenone-induced neurotoxicity in MES23. 5 dopaminergic cells. Peptides 69:109–114

    Article  CAS  Google Scholar 

  • Tang C-H, Fu X-J, Xu X-L, Wei X-J, Pan H-S (2012) The anti-inflammatory and anti-apoptotic effects of nesfatin-1 in the traumatic rat brain. Peptides 36:39–45

    Article  CAS  Google Scholar 

  • Tasatargil A, Kuscu N, Dalaklioglu S, Adiguzel D, Celik-Ozenci C, Ozdem S, Barutcigil A, Ozdem S (2017) Cardioprotective effect of nesfatin-1 against isoproterenol-induced myocardial infarction in rats: role of the Akt/gsk-3β pathway. Peptides 95:1–9

    Article  CAS  Google Scholar 

  • Thundimadathil J (2012) Cancer treatment using peptides: current therapies and future prospects. J Amino Acids 2012:1–13

    Article  Google Scholar 

  • Wang L, Du F, Wang X (2008) TNF-α induces two distinct caspase-8 activation pathways. Cell 133:693–703

    Article  CAS  Google Scholar 

  • White BC, Sullivan JM, Degracia DJ, O’Neil BJ, Neumar RW, Grossman LI, Rafols JA, Krause GS (2000) Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J Neurol Sci 179:1–33

    Article  CAS  Google Scholar 

  • Wicha P, Tocharus J, Janyou A, Jittiwat J, Changtam C, Suksamrarn A, Tocharus C (2017) Hexahydrocurcumin protects against cerebral ischemia/reperfusion injury, attenuates inflammation, and improves antioxidant defenses in a rat stroke model. PLoS One 12:e0189211

    Article  Google Scholar 

  • Xiao Y-F, Jie M-M, Li B-S, Hu C-J, Xie R, Tang B, Yang S-M (2015) Peptide-based treatment: a promising cancer therapy. J Immunol Res 2015:1–13

    Article  Google Scholar 

  • Zegers D, Beckers S, Mertens IL, Van Gaal LF, Van Hul W (2011) Association between polymorphisms of the Nesfatin gene, NUCB2, and obesity in men. Mol Genet Metab 103:282–286

    Article  CAS  Google Scholar 

  • Zhang A-Q, Li X-L, Jiang C-Y, Lin L, Shi R-H, Chen J-D, Oomura Y (2010) Expression of nesfatin-1/NUCB2 in rodent digestive system. World J Gastroenterol: WJG 16:1735–1741

    Article  CAS  Google Scholar 

  • Zhao TZ, Ding Q, Hu J, He SM, Shi F, Ma LT (2016) GPER expressed on microglia mediates the anti-inflammatory effect of estradiol in ischemic stroke. Brain and behavior 6:e00449

    Article  Google Scholar 

  • Zhu Y-M, Wang C-C, Chen L, Qian L-B, Ma L-L, Yu J, Zhu M-H, Wen C-Y, Yu L-N, Yan M (2013) Both PI3K/Akt and ERK1/2 pathways participate in the protection by dexmedetomidine against transient focal cerebral ischemia/reperfusion injury in rats. Brain Res 1494:1–8

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the grant No.95-03-130-29617from Iran University of Medical Sciences.

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Authors and Affiliations

  1. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

    Sohaila Erfani

  2. Rayan Center for Neuroscience and Behavior, Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

    Ali Moghimi

  3. Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Nahid Aboutaleb

  4. Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Nahid Aboutaleb

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

    Mehdi Khaksari

Authors
  1. Sohaila Erfani
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  2. Ali Moghimi
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  3. Nahid Aboutaleb
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  4. Mehdi Khaksari
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Correspondence to Nahid Aboutaleb.

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Erfani, S., Moghimi, A., Aboutaleb, N. et al. Protective effects of Nesfatin-1 peptide on cerebral ischemia reperfusion injury via inhibition of neuronal cell death and enhancement of antioxidant defenses. Metab Brain Dis 34, 79–85 (2019). https://doi.org/10.1007/s11011-018-0323-2

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