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

J Mol Neurosci. 2018 Jul;65(3):377-384. doi: 10.1007/s12031-018-1105-3. Epub 2018 Jun 28.

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.

Keywords: Brain ischemia; Microglial activation; Nesfatin-1; Spatial memory performance.

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy*
  • Calcium-Binding Proteins / administration & dosage
  • Calcium-Binding Proteins / pharmacology
  • Calcium-Binding Proteins / therapeutic use*
  • Caspase 3 / metabolism
  • DNA-Binding Proteins / administration & dosage
  • DNA-Binding Proteins / pharmacology
  • DNA-Binding Proteins / therapeutic use*
  • Male
  • Memory*
  • Microglia / drug effects*
  • Microglia / metabolism
  • Nerve Tissue Proteins / administration & dosage
  • Nerve Tissue Proteins / pharmacology
  • Nerve Tissue Proteins / therapeutic use*
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Nucleobindins
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*

Substances

  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Nucb1 protein, rat
  • Nucleobindins
  • Caspase 3