Jie Yu1 • Yao Cheng1 • Yaru Cui1 • Yujie Zhai1 • Wenshen Zhang2 • Mengdi Zhang1 • Wenyu Xin1 • Jia Liang1 • Xiaohong Pan1 • Qiaoyun Wang1 • Hongliu Sun

1 School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, China

2 The Sixth Scientifc Research Department, Shandong Institute of Nonmetallic Materials, Jinan 250031, China

 

Abstract

    An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the efects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specifc inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were signifcantly reversed by genipin administration. Our fndings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confrmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective efects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.

 

 

Keywords

Epilepsy; Seizure; Irisin; Genipin; Neuronal injury

 

[SpringerLink]