title: 5-HT6 Receptor Recruitment of mTOR Modulates Seizure Activity in Epilepsy.
abstract: Approximately 30% of epilepsy cases are refractory to current pharmacological treatments. Thus, novel therapeutic approaches that prevent or reverse the molecular and cellular mechanisms of epilepsy are required. 5-HT6 receptor (HTR6) blockade can modulate multiple neurotransmitter systems, and HTR6 may be a potential therapeutic treatment for neurological diseases, including epilepsy. Here, we investigated the role of HTR6 in epilepsy. We detected HTR6 expression both in human epileptic tissues and the pilocarpine rat model by western blotting. We observed behavioral changes after administration of pilocarpine in rats pretreated with a selective HTR6 antagonist, SB-399885, and recorded the electrophysiological index in the pilocarpine rat model pre- or posttreated with SB-399885 by electroencephalogram (EEG) and whole-cell clamp. We measured the activity of mammalian target of rapamycin (mTOR) in the pilocarpine rat model pretreated with the mTOR-specific inhibitor, rapamycin, and SB-399885 using western blotting. We found that HTR6 expression was upregulated in both human tissues and the pilocarpine rat model, and that SB-399885 could suppress epileptic seizures and mTOR activity in epileptic seizures. These results suggest that HTR6 plays an important role in modulating seizure activity and that the blockade of the HTR6/mTOR pathway could be a potential therapeutic target for epilepsy treatment.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Yaodong
authors.initials: Y
authors.lastname: Lv
authors.forename: Wanni
authors.initials: W
authors.lastname: Deng
authors.forename: Xi
authors.initials: X
authors.lastname: Peng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Xi
authors.forename: Guojun
authors.initials: G
authors.lastname: Chen
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D010862:Pilocarpine / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012640:Seizures / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D011985:Receptors, Serotonin; C097216:serotonin 6 receptor; D010862:Pilocarpine; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases