title: Upregulated dynamin 1 in an acute seizure model and in epileptic patients.
abstract: Dynamin 1 is a neuron-specific guanosine triphosphatase (GTPase) that is an essential component of membrane fission during synaptic vesicle recycling and endocytosis. This study evaluated the dynamin 1 expression pattern in the acute lithium-pilocarpine rat model and in patients with temporal lobe epilepsy (TLE) and investigated whether altering the dynamin 1 expression pattern affects epileptic seizures in vivo and in vitro. The immunofluorescence, western blot analysis, and reverse transcription-PCR results show that the dynamin 1 expression level increased significantly in experimental rats from day 1 to day 7 after the onset of seizures and was significantly higher in TLE patients. The behavioral study revealed that inhibiting dynamin 1 increased the latency time of the first seizure and decreased the frequency and severity of the seizures. In addition, electrophysiological recordings from brain slices showed that inhibiting dynamin 1 reduces the frequency of Mg-free induced seizure-like activity. The anticonvulsant effect of dynasore was more effective at 10 µM than at 1 µM or 160 µM. These results indicate that the altered level of dynamin 1 may contribute to the development of epileptic seizures and that the targeted regulation of dynamin 1 activity may control epileptic seizures.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Neurology, Chongqing, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Li
authors.forename: Xiao-Ni
authors.initials: XN
authors.lastname: Chen
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Fan
authors.forename: Yu-Jiao
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Gu
authors.forename: Xin-Wei
authors.initials: XW
authors.lastname: Fu
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Wang
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D058256:Brain Waves; D034284:Dynamin I / Q000235:genetics / Q000378:metabolism*; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use; D008094:Lithium / Q000633:toxicity; D008297:Male; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012640:Seizures / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation
chemical_list: D000927:Anticonvulsants; D006835:Hydrazones; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D010862:Pilocarpine; D008094:Lithium; D034284:Dynamin I
keywords: dynamin 1; dynasore; endocytosis; epilepsy