title: Rapamycin suppresses the recurrent excitatory circuits of dentate gyrus in a mouse model of temporal lobe epilepsy.
abstract: 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.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Tang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Long
authors.forename: Chang
authors.initials: C
authors.lastname: Zeng
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Fangfang
authors.initials: F
authors.lastname: Bi
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Qian
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000927:Anticonvulsants; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus