PMID- 25034463
OWN - NLM
STAT- MEDLINE
DCOM- 20160310
LR  - 20211203
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 51
IP  - 3
DP  - 2015
TI  - 5-HT6 Receptor Recruitment of mTOR Modulates Seizure Activity in Epilepsy.
PG  - 1292-9
LID - 10.1007/s12035-014-8806-6 [doi]
AB  - 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.
FAU - Wang, Liang
AU  - Wang L
AD  - Department of Neurology, The First Affiliated Hospital of Chongqing Medical 
      University, 1 You Yi Road, Chongqing, 400016, China.
FAU - Lv, Yaodong
AU  - Lv Y
FAU - Deng, Wanni
AU  - Deng W
FAU - Peng, Xi
AU  - Peng X
FAU - Xiao, Zheng
AU  - Xiao Z
FAU - Xi, Zhiqin
AU  - Xi Z
FAU - Chen, Guojun
AU  - Chen G
FAU - Wang, Xuefeng
AU  - Wang X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140718
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Receptors, Serotonin)
RN  - 0 (serotonin 6 receptor)
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Electroencephalography/methods
MH  - Epilepsy/drug therapy/metabolism/physiopathology
MH  - Humans
MH  - Male
MH  - Pilocarpine/*pharmacology
MH  - Rats, Sprague-Dawley
MH  - Receptors, Serotonin/*metabolism
MH  - Seizures/drug therapy/*metabolism/physiopathology
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2014/07/19 06:00
MHDA- 2016/03/11 06:00
CRDT- 2014/07/19 06:00
PHST- 2014/04/22 00:00 [received]
PHST- 2014/06/30 00:00 [accepted]
PHST- 2014/07/19 06:00 [entrez]
PHST- 2014/07/19 06:00 [pubmed]
PHST- 2016/03/11 06:00 [medline]
AID - 10.1007/s12035-014-8806-6 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2015;51(3):1292-9. doi: 10.1007/s12035-014-8806-6. Epub 2014 Jul 
      18.