Study On The Role Of HTR6/mTOR Signal Pathway On Epilepsy

Objective：Epilepsy is a common and refractory neurological disorder, but themolecular mechanisms underlying epilepsy remain unclear. Recent studies have shownthat the antagonism of5-HT6receptors (HTR6) can produce an anticonvulsant effect inthe rat maximal electroconvulsive shock test (MEST) and that HTR6may interact withthe mammalian target of rapamycin (mTOR), which is altered in several disorders thatare highly associated with epilepsy. Here, we investigated the specific relationshipbetween HTR6and mTOR and the potential role these molecules play in epilepsy.Methods：To achieve our objective, we utilized both human epileptic tissues andthe pilocarpine rat model, which is a widely used epilepsy model. Some rats werepretreated with a selective HTR6antagonist before being treated with pilocarpine.Results：Consistent with our findings in human epileptic tissue, we found thatHTR6expression was up-regulated in the pilocarpine model. Furthermore, mTOR wasaberrantly activated in the pilocarpine model, and this activation was markedly blockedby pretreatment with the HTR6antagonist. HTR6antagonist significantly increasedseizure latency and reduced seizure severity in pilocarpine-treated rats.Conclusion：This study suggested that HTR6may play an important role inepilepsy by activating mTOR and that HTR6/mTOR signaling may be a potentialtherapeutic target in epilepsy.