Effects of Anti-Seizure Medication on Neuregulin-1 Gene and Protein in Patients with First-Episode Focal Epilepsy

Abstract

Xin Zhao,1,2 Guijiang Huang,2 Zhenrong Xie,2 Yaxiong Mo,3 Hongxuan Zhu,2 Yajie Gao,2 Yanbing Han,4 Wei Tang2 1Department of Pharmacy, The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou, People’s Republic of China; 2Department of Science and Education, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Department of Pediatrics, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of ChinaCorrespondence: Wei Tang, Department of Science and Education, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, People’s Republic of China, Email [email protected] Yanbing Han, Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, People’s Republic of China, Email [email protected]: Neuregulin-1 (NRG-1) appears to play a role in the pathogenesis of several neuropsychiatric disorders, including epilepsy. We conducted a study to investigate the effect of anti-seizure medication on NRG-1 mRNA and NRG-1 protein levels in patients with first-episode focal epilepsy.Methods: The levels of NRG-1 mRNA isoforms (type I, II, III, and IV) in peripheral blood mononuclear cells (PBMCs) of 39 healthy controls, 39 first-episode focal epilepsy patients before anti-seizure medication (ASM) therapy and four weeks after administration of ASM were measured by RT-qPCR, and the levels of NRG-1 protein in the serum of samples of each group were determined using ELISA. In addition the relationship between efficacy, NRG-1 mRNA expression, and NRG-1 protein expression was analyzed.Results: The levels of NRG-1 mRNA progressively increased in patients with first-episode focal epilepsy treated with ASM and were distinctly different from those before medication, but remained lower than in healthy controls (all P < 0.001). Before and after drug administration, NRG-1 protein levels were substantially higher in epileptic patients than in healthy controls, and no significant changes were detected with prolonged follow-up (P < 0.001). Patients with epilepsy who utilized ASM were able to control seizures with an overall efficacy of 97.4%. There was a negative correlation between NRG-1 mRNA levels and efficacy: as NRG-1 mRNA levels increased, seizures reduced (all P < 0.05).Conclusion: Our research indicated that NRG-1 may play a role in the pathophysiology of epilepsy. NRG-1 mRNA may provide ideas for the discovery of novel epilepsy therapeutic markers and therapeutic targets for novel ASM.Keywords: neuregulin-1, focal epilepsy, drug treatment, pathophysiology

Keywords

• neuregulin-1
• focal epilepsy
• drug treatment
• pathophysiology