Cytisine Exerts an Anti-Epileptic Effect via α7nAChRs in a Rat Model of Temporal Lobe Epilepsy

Frontiers in Pharmacology

Wei-dong Ji¹  Jia-gui Zhong²  Wei Li²  Ji-qiang Ding²  Shu-qiao He³  Jing-jun Zheng⁴  De-feng Qi⁵  Teng-yue Zhang⁶  Jing-xian Deng⁶  Xin Zhao⁶  Mei Zhang⁶  Jing-mei Teng⁶  Xu Qian⁶  Ze-xin Huang⁶  Hong-tao Liu⁶  Xin-wen Sheng⁶ 

[1] Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, China;Department of Pharmacy, Maoming People’s Hospital, Maoming, China;Department of Pharmacy, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, China;Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hop-ital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, Guangzhou, China;Key Laboratory of Molecular Target and Clinical Pharmacology, Department of Clinical Pharmacology, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China;

关键词: cytisine;    temporal lobe epilepsy;    neuroprotection;    synaptic remodeling;    cholinergic transmission;    α7nAChRs;   

DOI  :  10.3389/fphar.2021.706225

来源: DOAJ

【 摘 要 】

Background and Purpose: Temporal lobe epilepsy (TLE) is a common chronic neurological disease that is often invulnerable to anti-epileptic drugs. Increasing data have demonstrated that acetylcholine (ACh) and cholinergic neurotransmission are involved in the pathophysiology of epilepsy. Cytisine, a full agonist of α7 nicotinic acetylcholine receptors (α7nAChRs) and a partial agonist of α4β2nAChRs, has been widely applied for smoking cessation and has shown neuroprotection in neurological diseases. However, whether cytisine plays a role in treating TLE has not yet been determined.Experimental Approach: In this study, cytisine was injected intraperitoneally into pilocarpine-induced epileptic rats for three weeks. Alpha-bungarotoxin (α-bgt), a specific α7nAChR antagonist, was used to evaluate the mechanism of action of cytisine. Rats were assayed for the occurrence of seizures and cognitive function by video surveillance and Morris water maze. Hippocampal injuries and synaptic structure were assessed by Nissl staining and Golgi staining. Furthermore, levels of glutamate, γ-aminobutyric acid (GABA), ACh, and α7nAChRs were measured.Results: Cytisine significantly reduced seizures and hippocampal damage while improving cognition and inhibiting synaptic remodeling in TLE rats. Additionally, cytisine decreased glutamate levels without altering GABA levels, and increased ACh levels and α7nAChR expression in the hippocampi of TLE rats. α-bgt antagonized the above-mentioned effects of cytisine treatment.Conclusion and Implications: Taken together, these findings indicate that cytisine exerted an anti-epileptic and neuroprotective effect in TLE rats via activation of α7nAChRs, which was associated with a decrease in glutamate levels, inhibition of synaptic remodeling, and improvement of cholinergic transmission in the hippocampus. Hence, our findings not only suggest that cytisine represents a promising anti-epileptic drug, but provides evidence of α7nAChRs as a novel therapeutic target for TLE.

【 授权许可】

Unknown