Skip to main content

Advertisement

Log in

Nesfatin-1 Improve Spatial Memory Impairment Following Transient Global Cerebral Ischemia/Reperfusion via Inhibiting Microglial and Caspase-3 Activation

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Nesfatin-1, a recently discovered peptide, is involved in important functions such as food intake regulation and energy homeostasis. Previous studies have demonstrated that it has protective effects following myocardial injury and also protects dopaminergic cells against neurotoxicity with the anti-inflammatory and anti-apoptotic mechanisms. In this study, we aimed to assay the neuroprotective effects of Nesfatin-1 after brain ischemia/reperfusion. Twenty-eight male Wistar rats were randomly selected and allocated in the form of four groups (sham, Nesfatin-1, ischemia, ischemia+Nesfatin-1). Ischemia was created by obstruction couple common carotid arteries in 20-min period. Saline as a vehicle and Nesfatin-1 (20 μg/kg, intraperitoneally) were injected at the time of reperfusion. Spatial memory performances were evaluated by the Morris water maze. The level of protein expression was determined by immunohistochemical and immunofluorescence staining. Nesfatin-1 significantly reduced caspase-3 (P < 0.01) and microglial activation (P < 0.01) and improved spatial memory impairments (P < 0.05) induced by brain ischemia. Nesfatin-1 has significant neuroprotective effects and can be introduced as a therapeutic agent against cerebral ischemia-induced injuries.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

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  PubMed  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 Clin Neurosci 7:21

    PubMed  PubMed Central  CAS  Google Scholar 

  • Ayada C, Toru Ü, Korkut Y (2015) Nesfatin-1 and its effects on different systems. Hippokratia 19:4–10

    PubMed  PubMed Central  CAS  Google Scholar 

  • Bonnet MS, Pecchi E, Trouslard J, Jean A, Dallaporta M, Troadec J-D (2009) Central nesfatin-1-expressing neurons are sensitive to peripheral inflammatory stimulus. J Neuroinflammation 6:27

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chan PH (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 21:2–14

    Article  PubMed  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  PubMed  PubMed Central  CAS  Google Scholar 

  • Chu K, Yin B, Wang J, Peng G, Liang H, Xu Z, Du Y, Fang M, Xia Q, Luo B (2012) Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus. J Neuroinflammation 9:69

    PubMed  PubMed Central  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  PubMed  CAS  Google Scholar 

  • Feuerstein G, Liu T, Barone F (1994) Cytokines, inflammation, and brain injury: role of tumor necrosis factor-alpha. Cerebrovasc Brain Metab Rev 6:341–360

    PubMed  CAS  Google Scholar 

  • Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D (2011) Vascular contributions to cognitive impairment and dementia. Stroke 42:2672–2713

    Article  PubMed  PubMed Central  Google Scholar 

  • Hovens IB, Nyakas C, Schoemaker RG (2014) A novel method for evaluating microglial activation using ionized calcium-binding adaptor protein-1 staining: cell body to cell size ratio. Neuroimmunol Neuroinflammation 1:82

    Article  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

    Article  PubMed  PubMed Central  Google Scholar 

  • Ito D, Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y, Kohsaka S (1998) Microglia-specific localisation of a novel calcium binding protein, Iba1. Mol Brain Res 57:1–9

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Jin R, Yang G, Li G (2010) Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 87:779–789

    Article  PubMed  PubMed Central  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  PubMed  CAS  Google Scholar 

  • Kolgazi M, Cantali-Ozturk C, Deniz R, Ozdemir-Kumral ZN, Yuksel M, Sirvanci S, Yeğen BC (2015) Nesfatin-1 alleviates gastric damage via direct antioxidant mechanisms. J Surg Res 193:111–118

    Article  PubMed  CAS  Google Scholar 

  • Lakhan SE, Kirchgessner A, Hofer M (2009) Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med 7:97

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Le DA, Wu Y, Huang Z, Matsushita K, Plesnila N, Augustinack JC, Hyman BT, Yuan J, Kuida K, Flavell RA (2002) Caspase activation and neuroprotection in caspase-3-deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation. Proc Natl Acad Sci 99:15188–15193

    Article  PubMed  CAS  Google Scholar 

  • Lee SH, Chun W, Kong PJ, Han JA, Cho BP, Kwon O-Y, Lee HJ, Kim SS (2006) Sustained activation of Akt by melatonin contributes to the protection against kainic acid-induced neuronal death in hippocampus. J Pineal Res 40:79–85

    Article  PubMed  CAS  Google Scholar 

  • Li WL, Cai HH, Wang B, Chen L, Zhou QG, Luo CX, Liu N, Ding XS, Zhu DY (2009) Chronic fluoxetine treatment improves ischemia-induced spatial cognitive deficits through increasing hippocampal neurogenesis after stroke. J Neurosci Res 87:112–122

    Article  PubMed  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  PubMed  PubMed Central  CAS  Google Scholar 

  • Lotfiaski M, Rezvani ME, Khaksari M, Hafizi Z, Pirmoradi Z, Niknazar S, Zaremehrjerdi F (2017) Neuroprotective effect of berberine chloride on cognitive impairment and hippocampal damage in experimental model of vascular dementia. Iran J Basic Med Sci 21(1):53–58

  • Maleki SN, Aboutaleb N, Souri F (2017) Berberine confers neuroprotection in coping with focal cerebral ischemia by targeting inflammatory cytokines. J Chem Neuroanat 87:54–59

  • 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  CAS  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  PubMed  Google Scholar 

  • Pałasz A, Krzystanek M, Worthington J, Czajkowska B, Kostro K, Wiaderkiewicz R, Bajor G (2012) Nesfatin-1, a unique regulatory neuropeptide of the brain. Neuropeptides 46:105–112

    Article  PubMed  CAS  Google Scholar 

  • Pan W, Hsuchou H, Kastin AJ (2007) Nesfatin-1 crosses the blood–brain barrier without saturation. peptides 28:2223–2228

    Article  PubMed  CAS  Google Scholar 

  • Shah IM, Macrae IM, Di Napoli M (2009) Neuroinflammation and neuroprotective strategies in acute ischaemic stroke-from bench to bedside. Curr Mol Med 9:336–354

    Article  PubMed  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  PubMed  PubMed Central  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

  • Shih P-C, Yang Y-R, Wang R-Y (2013) Effects of exercise intensity on spatial memory performance and hippocampal synaptic plasticity in transient brain ischemic rats. PLoS One 8:e78163

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stoll G, Kleinschnitz C, Nieswandt B (2010) Combating innate inflammation: a new paradigm for acute treatment of stroke? Ann N Y Acad Sci 1207:149–154

    Article  PubMed  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  PubMed  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  PubMed  CAS  Google Scholar 

  • Wadowska M, Woods J, Rogozinska M, Briones TL (2015) Neuroprotective effects of enriched environment housing after transient global cerebral ischaemia are associated with the upregulation of insulin-like growth factor-1 signalling. Neuropathol Appl Neurobiol 41:544–556

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhao EY, Efendizade A, Cai L, Ding Y (2016) The role of Akt (protein kinase B) and protein kinase C in ischemia–reperfusion injury. Neurol Res 38:301–308

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

This study was supported by a grant No. 3/42964 from the Ferdowsi University of Mashhad research affairs.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ali Moghimi.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Erfani, S., Moghimi, A., Aboutaleb, N. et al. Nesfatin-1 Improve Spatial Memory Impairment Following Transient Global Cerebral Ischemia/Reperfusion via Inhibiting Microglial and Caspase-3 Activation. J Mol Neurosci 65, 377–384 (2018). https://doi.org/10.1007/s12031-018-1105-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-018-1105-3

Keywords

Navigation