PMID- 22414694 OWN - NLM STAT- MEDLINE DCOM- 20120516 LR - 20211203 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 420 IP - 1 DP - 2012 Mar 30 TI - Rapamycin suppresses the recurrent excitatory circuits of dentate gyrus in a mouse model of temporal lobe epilepsy. PG - 199-204 LID - 10.1016/j.bbrc.2012.02.143 [doi] AB - Recurrent excitatory circuits and abnormal recurrent excitatory inputs are essential in epileptogenesis. Studies in temporal lobe epilepsy have shown that mossy fiber sprouting, which represents synaptic reorganization, renders the formation of abnormal recurrent excitatory circuits and inputs. The mammalian target of rapamycin (mTOR) pathway has recently been proved important in mossy fiber sprouting. In the present study, rapamycin, a mTOR inhibiter, was injected into the mouse of temporal lobe epilepsy. Electrophysiological and histological properties of the hippocampus were investigated by whole cell patch clamp, extracellular recording and Timm staining. Following the development of epilepsy, frequency of spontaneous excitatory postsynaptic currents (EPSCs) and amplitude of antidromically evoked EPSCs in granule cells were remarkably increased, as well as the epileptiform activity and mossy fiber sprouting were detected, which indicated the formation of abnormal recurrent excitatory circuits. By the use of rapamycin, frequency of spontaneous EPSCs, amplitude of antidromically evoked EPSCs, the epileptiform activity and mossy fiber sprouting were all remarkably suppressed. Our findings suggested an anti-epileptogenic role of rapamycin by suppressing the recurrent excitatory circuits of dentate gyrus. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Tang, Haiyun AU - Tang H AD - Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. FAU - Long, Hongyu AU - Long H FAU - Zeng, Chang AU - Zeng C FAU - Li, Yi AU - Li Y FAU - Bi, Fangfang AU - Bi F FAU - Wang, Jinhui AU - Wang J FAU - Qian, Hao AU - Qian H FAU - Xiao, Bo AU - Xiao B LA - eng PT - Journal Article DEP - 20120303 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Anticonvulsants) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Anticonvulsants/*pharmacology MH - Dentate Gyrus/*drug effects/physiopathology MH - Disease Models, Animal MH - Epilepsy, Temporal Lobe/*physiopathology MH - Excitatory Postsynaptic Potentials/*drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Nerve Fibers/drug effects/physiology MH - Sirolimus/*pharmacology MH - TOR Serine-Threonine Kinases/antagonists & inhibitors EDAT- 2012/03/15 06:00 MHDA- 2012/05/17 06:00 CRDT- 2012/03/15 06:00 PHST- 2012/02/22 00:00 [received] PHST- 2012/02/27 00:00 [accepted] PHST- 2012/03/15 06:00 [entrez] PHST- 2012/03/15 06:00 [pubmed] PHST- 2012/05/17 06:00 [medline] AID - S0006-291X(12)00402-0 [pii] AID - 10.1016/j.bbrc.2012.02.143 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2012 Mar 30;420(1):199-204. doi: 10.1016/j.bbrc.2012.02.143. Epub 2012 Mar 3.