Anti-Seizure and Neuronal Protective Effects of Irisin in Kainic Acid-Induced Chronic Epilepsy Model with Spontaneous Seizures.
10.1007/s12264-022-00914-w
- Author:
Jie YU
1
;
Yao CHENG
1
;
Yaru CUI
1
;
Yujie ZHAI
1
;
Wenshen ZHANG
2
;
Mengdi ZHANG
1
;
Wenyu XIN
1
;
Jia LIANG
1
;
Xiaohong PAN
1
;
Qiaoyun WANG
3
;
Hongliu SUN
4
Author Information
1. School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, 264003, China.
2. The Sixth Scientific Research Department, Shandong Institute of Nonmetallic Materials, Jinan, 250031, China.
3. School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, 264003, China. byylwqy@163.com.
4. School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, 264003, China. sun_china6@163.com.
- Publication Type:Journal Article
- Keywords:
Epilepsy;
Genipin;
Irisin;
Neuronal injury;
Seizure
- MeSH:
Rats;
Animals;
Kainic Acid/toxicity*;
Brain-Derived Neurotrophic Factor/metabolism*;
Fibronectins/metabolism*;
Hippocampus/metabolism*;
Rats, Sprague-Dawley;
Epilepsy/metabolism*;
Seizures/prevention & control*
- From:
Neuroscience Bulletin
2022;38(11):1347-1364
- CountryChina
- Language:English
-
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 effects 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 specific 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 significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects 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.
