[1]伏鹏飞,温跃桃,王刚,等.FBXL20在颞叶癫痫患者及癫痫大鼠模型中的表达变化[J].第三军医大学学报,2016,38(11):1257-1262.
 Fu Pengfei,Wen Yuetao,Wang Gang,et al.Altered expression of FBXL20 in temporal lobe epilepsy patients and pilocarpine-induced rat model[J].J Third Mil Med Univ,2016,38(11):1257-1262.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
38卷
期数:
2016年第11期
页码:
1257-1262
栏目:
基础医学
出版日期:
2016-06-15

文章信息/Info

Title:
Altered expression of FBXL20 in temporal lobe epilepsy patients and pilocarpine-induced rat model
作者:
伏鹏飞温跃桃王刚高超谢延风詹彦石全红
重庆医科大学附属第一医院神经外科
Author(s):
Fu Pengfei Wen Yuetao Wang Gang Gao Chao Xie Yanfeng Zhan Yan Shi Quanhong

Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

关键词:
FBXL20RIM1颞叶癫痫泛素化突触重塑突触囊泡
Keywords:
FBXL20 RIM1 temporal lobe epilepsy ubiquitination synapse plasticity synaptic vesicle
分类号:
R341; R741.02; R742.1
文献标志码:
A
摘要:

目的      通过研究E3泛素连接酶FBXL20及其下游蛋白-神经元突触膜胞外分泌调节蛋白1(regulating synaptic membrane exocytosis 1,RIM1)在颞叶癫痫患者皮质及匹鲁卡品癫痫大鼠模型皮质、海马组织中的表达变化,探讨FBXL20在癫痫形成中的作用。      方法      以颞叶癫痫患者手术切除病灶标本(n=25)为癫痫组,以脑外伤减压手术所切皮质标本(n=10)为对照组。另取40只健康雄性SD大鼠腹腔注射氯化锂(127 mg/kg),20 h后腹腔注射匹鲁卡品(50 mg/kg),每30分钟重复给予1次匹鲁卡品(10 mg/kg),直到大鼠癫痫发作。2周后出现癫痫自发性发作的大鼠纳入癫痫组;2个月后仍未出现癫痫自发性发作的大鼠纳入对照组。采用免疫荧光对FBXL20的表达进行定位;免疫组化检测FBXL20的表达水平;Western blot检测FBXL20、RIM1的表达水平。      结果      免疫荧光检测结果显示FBXL20主要表达于神经元;免疫组化及Western blot检测结果均显示癫痫患者皮质、癫痫大鼠模型皮质与海马中FBXL20表达较对照组明显下降(P<0.05);同时Western blot检测结果显示RIM1表达较对照组明显升高(P<0.05)。      结论      FBXL20在癫痫患者及大鼠模型中的表达水平明显降低,RIM1表达明显升高,提示FBXL20可能通过调控RIM1参与了癫痫的形成。

Abstract:

Objective      To investigate the role of E3 ubiquitin ligase FBXL20 in the epileptogenesis through detecting the expression level of FBXL20 and its downstream regulating synaptic membrane exocytosis 1 (RIM1) in brain tissue of temporal lobe epilepsy patients and pilocarpine-induced rat model.       Methods      Epilepsy focus resected from temporal lobe epilepsy patients was taken as the epilepsy group (n=25), and the cortex resected from brain trauma patients was taken as the control group (n=10). Forty male, healthy SD rats were injected with pilocarpine (127 mg/kg). The rats with spontaneous seizures in 2 weeks later were selected into the epilepsy model group, while those without spontaneous seizures until 2 months later were selected into the control group. FBXL20 and RIM1 in the human brain cortex and rat cortex and hippocampus were detected by immunofluorescence staining, Western blotting and immunohistochemistry assay.       Results      Immunofluorescence staining showed that FBXL20 mainly located in the neurons. Immunohistochemistry assay and Western blotting showed that the expression of FBXL20 was down-regulated in the epilepsy group (P<0.05). Western blotting indicated that expression of RIM1 was up-regulated in the epilepsy group (P<0.05).       Conclusion      Altered expression of FBXL20 indicates that FBXL20 may be involved in the epileptogenesis.

参考文献/References:

[1]Leach J P, Abassi H. Modern management of epilepsy[J]. Clin Med (Lond), 2013, 13(1): 84-86.
[2]Dulac O, Milh M, Holmes G L. Brain maturation and epilepsy[J]. Handb Clin Neurol, 2013, 111: 441-446. DOI: 10.1016/B978-0-444-52891-9.00047-6
[3]Cousin M A, Robinson P J. Mechanisms of synaptic vesicle recycling illuminated by fluorescent dyes[J]. J Neurochem, 1999, 73(6): 2227-2239.
[4]Martin B S, Huntsman M M. Pathological plasticity in fragile X syndrome[J]. Neural Plast, 2012, 2012: 275630. DOI: 10.1155/2012/275630
[5]Holderith N, Lorincz A, Katona G, et al. Release probability of hippocampal glutamatergic terminals scales with the size of the active zone[J]. Nat Neurosci, 2012, 15(7): 988-997. DOI: 10.1038/nn.3137
[6]Frank C A. How voltage-gated calcium channels gate forms of homeostatic synaptic plasticity[J]. Front Cell Neurosci, 2014, 8: 40. DOI: 10.3389/fncel.2014.00040
[7]Upreti C, Otero R, Partida C, et al. Altered neurotransmitter release, vesicle recycling and presynaptic structure in the pilocarpine model of temporal lobe epilepsy[J]. Brain, 2012, 135(Pt 3): 869-885. DOI: 10.1093/brain/awr341
[8]Janz R, Goda Y, Geppert M, et al. SV2A and SV2B function as redundant Ca2+ regulators in neurotransmitter release[J]. Neuron, 1999, 24(4): 1003-1016.
[9]Nowack A, Malarkey E B, Yao J, et al. Levetiracetam reverses synaptic deficits produced by overexpression of SV2A[J]. PLoS One, 2011, 6(12): e29560. DOI: 10.1371/journal.pone.0029560
[10]Yao I, Takagi H, Ageta H, et al. SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release[J]. Cell, 2007, 130(5): 943-957. DOI: 10.1016/j.cell.2007.06.052
[11]Girach F, Craig T J, Rocca D L, et al. RIM1α SUMOylation is required for fast synaptic vesicle exocytosis[J]. Cell Rep, 2013, 5(5): 1294-1301. DOI: 10.1016/j.celrep.2013.10.039
[12]Pitsch J, Opitz T, Borm V, et al. The presynaptic active zone protein RIM1α controls epileptogenesis following status epilepticus[J]. J Neurosci, 2012, 32(36): 12384-12395. DOI: 10.1523/JNEUROSCI.0223-12.2012
[13]Xu X, Yang X, Xiong Y, et al. Increased expression of receptor for activated C kinase 1 in temporal lobe epilepsy[J]. J Neurochem, 2015, 133(1): 134-143. DOI: 10.1111/jnc.13052
[14]詹傲, 石全红, 张超, 等. Fascin-1在颞叶癫痫大鼠中表达的变化[J]. 第三军医大学学报, 2014, 36(15): 1587-1591. DOI: 10.16016/j.1000-5404.2014.15.023
[15]Covolan L, Mello L E. Temporal profile of neuronal injury following pilocarpine or kainic acid-induced status epilepticus[J]. Epilepsy Res, 2000, 39(2): 133-152.
[16]吴彬, 孙红斌. 海马苔藓纤维出芽与癫痫[J]. 实用医院临床杂志, 2012, 9(1): 133-135. DOI: 10.3969/j.issn.1672-6170.2012.01.051.
[17]Dobie F, Craig A M. A fight for neurotransmission: SCRAPPER trashes RIM[J]. Cell, 2007, 130(5): 775-777. DOI: 10.1016/j.cell.2007.08.020
[18]Han Y, Kaeser P S, Sudhof T C, et al. RIM determines Ca2+ channel density and vesicle docking at the presynaptic active zone[J]. Neuron, 2011, 69(2): 304-316. DOI: 10.1016/j.neuron.2010.12.014
[19]Kiyonaka S, Wakamori M, Miki T, et al. RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels[J]. Nat Neurosci, 2007, 10(6): 691-701. DOI: 10.1038/nn1904
[20]Xanthos D N, Sandkuhler J. Neurogenic neuroinflammation: inflammatory CNS reactions in response to neuronal activity[J]. Nat Rev Neurosci, 2014, 15(1): 43-53. DOI: 10.1038/nrn3617
[21]Setou M, Yao I. SCRAPPER: an F-box protein that regulates synaptic vesicle release via RIM1 degradation[J]. Tanpakushitsu Kakusan Koso, 2008, 53(1): 36-43.
[22]Takagi H, Setou M, Ito S, et al. SCRAPPER regulates the thresholds of long-term potentiation/depression, the bidirectional synaptic plasticity in hippocampal CA3-CA1 synapses[J]. Neural Plast, 2012, 2012: 352829. DOI: 10.1155/2012/352829
[23]Yao I, Takao K, Miyakawa T, et al. Synaptic E3 ligase SCRAPPER in contextual fear conditioning: extensive behavioral phenotyping of Scrapper heterozygote and overexpressing mutant mice[J]. PLoS One, 2011, 6(2): e17317. DOI: 10.1371/journal.pone.0017317

更新日期/Last Update: 2016-05-29