Anticonvulsant and neuroprotective effects of apelin-13 on pentylenetetrazole-induced seizures in male rats

Biomed Pharmacother. 2016 Dec;84:258-263. doi: 10.1016/j.biopha.2016.09.048. Epub 2016 Sep 21.


Epilepsy is a common neurological disorder with no effective treatment or cure. Neuropeptide apelin is an endogenous ligand of angiotensin receptor-like 1 (APJ). It has been shown that apelin has protective and anti-neurodegenerative properties. This study was designed to evaluate the effect of apelin-13 on pentylenetetrazole (PTZ)-induced rat model of seizure. Adult male Wistar rats were divided into the experimental groups as follows: control group receiving PTZ; apelin-treated group which received apelin-13 before PTZ; apelin+F13A-treated group which received apelin-13 plus the apelin receptor antagonist (F13A) before PTZ; apelin+naloxone group which received apelin-13+naloxone before PTZ. Behavioral scoring was used to access seizure. The expression level of APJ was measured by western blotting. Neuronal degeneration, apoptosis and astrocyte activation were evaluated by vanadium acid fuchsin (VAF) staining and immunohistochemistry. Our data demonstrated that apelin-13 pretreatment significantly inhibited seizure threshold (p<0.001) and tonic-clonic latency (p<0.001) compared with the control group. In addition, PTZ-induced up-regulation of APJ was attenuated by apelin-13 treatment. Histological and immunohistochemical findings also showed that apelin-13 could protect cortical neurons against PTZ-induced neuroinflammation and apoptosis. In conclusion, apelin-13 has anticonvulsive and neuroprotective properties against PTZ-induced seizure in rats and provided a new pharmacological aspect of the neuropeptide apelin.

Keywords: Apelin-13; Pentylenetetrazole; Rats; Seizure.

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Apelin Receptors
  • Apoptosis
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / metabolism
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Male
  • Nerve Degeneration*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Pentylenetetrazole*
  • Rats, Wistar
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism
  • Seizures / chemically induced
  • Seizures / pathology
  • Seizures / physiopathology
  • Seizures / prevention & control*


  • Anticonvulsants
  • Apelin Receptors
  • Aplnr protein, rat
  • Glial Fibrillary Acidic Protein
  • Intercellular Signaling Peptides and Proteins
  • Neuroprotective Agents
  • Receptors, G-Protein-Coupled
  • apelin-13 peptide
  • apelin-13, Ala(13)-
  • Pentylenetetrazole