期刊文献+

难治性癫痫模型大鼠脑组织中srGAP2分子的表达 被引量:2

Abnormal expression of srGAP2 in the brain of rats with refractory epilepsy
暂未订购
导出
摘要 背景:众多研究结果显示srGAP2分子在突起生长和突触可塑性起到关键的作用,但具体机制不明。目的:检测srGAP2在致痫大鼠模型中的表达,探讨srGAP2与难治性癫痫发病机制的相关性。方法:选取雄性SD大鼠56只随机分为7组,其中随机选取6组建立癫痫模型,构成实验组,剩余1组作为对照组。分别选取癫痫发作后的6h、1d、1周、2周、1个月、2个月等6个时间点的颞叶脑组织作为研究对象,并与对照组进行比较。利用免疫组织化学、免疫荧光以及免疫印迹3种方法检测srGAP2在致痫动物模型以及对照组的脑组织中的表达及变化规律。结果与结论:实验组中srGAP2除在皮质区表达增高外,还在海马区高表达,与对照组相比各时间点srGAP2在颞叶癫痫动物组中的表达含量逐渐升高,且在2周左右达高峰并维持,到2个月左右降至接近对照组水平。结果提示srGAP2可能通过促进苔藓纤维出芽,进而导致脑组织中异常神经网络的建立,并最终在难治性癫痫的发生发展中起到重要作用。 BACKGROUND: Many studies show srGAP2 molecules play a key role in neurite outgrowth and synaptic plasticity, but the exact mechanism is unknown. OBJECTIVE: To study the possible correlation between srGAP2 expression and epilepsy pathogenesis through testing the expression of srGAP2 in epileptic rats. METHODS: Fifty-six Sprague-Dawley male rats were divided randomly into seven groups, including six groups with epilepsy induced by lithium-pilocarpine management and one control group. The samples oftemporal lobe tissue were taken from rats at 6 hours, 1 day, 1 week, 2 Weeks, 1 month, and 2 months after seizures, and from controls group. Using immunohistochemistry, immunefluorescence, and western-blot methods, we tested the expression of srGAP2 in experimental animals and control groups. RESULTS AND CONCLUSION: Western blotting of rat brain tissue showed that srGAP2 was up-regulated in the cortex and hippocampus of the epileptic rats as compared with the control rats. The maximal expression was seen at about 2 weeks, and relatively high expression maintained until 1 month. The expression then returned down, and approached normal levels at 2 months. These results were consistent with the immunohistochemical and immunofluorescence results. These data implicate srGAP2 may promote mossy fiber sprouting, and participate in the abnormal development of synapses. The result suggests that this protein may play an important role in the pathogenesis of intractable epilepsy.
出处 《中国组织工程研究》 CAS CSCD 2013年第7期1207-1211,共5页 Chinese Journal of Tissue Engineering Research
关键词 组织构建 组织构建实验造模 难治性癫痫 srGAP2 苔藓纤维出芽 癫痫模型 脑组织 细胞生物 分子生物学 组织构建图片文章 tissue construction experimental modeling in tissue construction refractory epilepsy srGAP2 mossy fiber sprouting epilepsy models brain tissue cellular biology molecular biology tissue constructionphotographs-containing paper
  • 相关文献

参考文献16

  • 1Ribak CE,Seress L,Weber P. Alumina gel injections into the temporal lobe of rhesus monkeys cause complex partial seizures and morphological changes found in human temporal lobe epilepsy[J].{H}Journal of Comparative Neurology,1998,(02):266-290.
  • 2Nadler JV,Okazaki MM,Gruenthal M. Kainic acid seizures and neuronal cel death:insights from studies of selective lesions and Drugs[J].{H}Advances in Experimental Medicine and Biology,1986.673-686.
  • 3Post RM,Weiss SR. Convergences in course of il ness and treatments of the epilepsies and recurrent affective disorders[J].{H}CLINCAL EEG AND NEUROSCIENCE,2004,(01):14-24.
  • 4朱遂强,杨嘉君,杜鹏,王开颜,阮旭中.戊四氮点燃过程中大鼠海马苔藓纤维发芽变化的研究[J].中国康复,2004,19(1):6-8. 被引量:4
  • 5Lynch M,Sutula T. Recurrent excitatory connectivity in the dentate gyrus of kindled and kainic acid-treated rats[J].{H}Journal of Neurophysiology,2000,(02):693-704.
  • 6Soderling SH,Guire ES,Kaech S. A WAVE-1 and WRP signaling complex regulates spine density,synaptic plasticity,and memory[J].{H}Journal of Neuroscience,2007,(02):355-365.
  • 7Racine RJ. Modification of seizure activity by electrical stimulation[J].{H}NEUROPHYSIOLOGY,1972,(03):281-294.
  • 8Sabrice Guerrier,Jaeda Coutinho-Budd,Takayuki Sassa. The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis[J].Cel,2009,(05):990-1004.
  • 9Saitsu H,Osaka H,Sugiyama S. Early infantile epileptic encephalopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2(SRGAP2)[J].American Journal of Medical Genetics Part,2011,(01):199-205.
  • 10Ayala R,Shu T,Tsai LH. Trekking across the brain:the journey of neuronal migration[J].Cel,2007.29-43.

二级参考文献6

  • 1[1]Gorm Danscher and J ens Zimmer. An important Timm sulphide silver method for light and electron microscopic localization of heavy metals in biological tissue[J]. Histochemistry, 1978, 55: 7- 40.
  • 2[2]Gregory L, Homes MS, Yehezkel B, et al. Mossy fiber sprouting after recurrent seizures during early development in rats[J]. J Comp Neurol, 1999, 404:537-553.
  • 3[3]Pierce JP, Milner, FA. Parallel increases in the synaptic and surface areas of mossy fiber terminals following seizure induction[J]. J Neurosi, 2001, 20: 77-86.
  • 4[4]Sutala Z,Acsady L,Kamondi A, et al. Network properties of dentate gyrus in epileptic rats with hilar neuron loss and granule cell axon reorganization [J]. J Neurophysiol, 1997, 77: 2685 - 2711.
  • 5[5]Mathern GW, BereramⅢ EH, Babb TL. In contrast to kindled seizures, the frequency of spontaneous epilepsy in the limbic status model correlates with greater aberrant fascia dentate excitatory and inhibitory axon sprouting and increased staining for NMDA, AMPA and GABA receptors [J]. Neuroscicnc, 1999, 35:1003-1019.
  • 6[6]Zhang Xia, Cui Sbu-Sen, Amy E, et al. Relations between brain pathlogy and temporal lobe epilepsy[J]. J Neurosci, 2002, 22: 6052- 6061.

共引文献3

同被引文献18

  • 1Saitsu H, OsakaH, Sugiyama S. Early infantile epileptic eneepha- lopathy associatedwith the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2) [ J]. Am J Med Genet A. 2012, 158 : 199 - 205.
  • 2Dennis MY, Nuttle X, Sudmant PH. et al. Evolution of human-spe- cific neural SRGAP 2 genes by incomplete segmental duplication [J]. Cell, 2012, 149:912 -922.
  • 3Ribak CE, Seress L, Weber P, et al. Alumina gel injections into the temporal lobe of rhesus monkeys cause complex partial seizures and morphological changes found in human temporal lobe epilepsy [J]. J Comp Neurol, 1998, 401:266 -290.
  • 4Guerrier S, Coutinho-Budd J, Sassa T, et al. The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migra- tion and morphogenesis[ J]. Cell, 2009, 138: 990- 1004.
  • 5Chattier C, Polleux F. How human-specific SRGAP2 gone duplica- tions control human brain development [ J ]. Med Sci (Paris), 2012, 28:911 -914.
  • 6Chattier C, Joshi K, Coutinho-Budd J. Inhibition of SRGAP2 func-tion by its human-specific paralogs induces neoteny during spine maturation[ J]. Cell, 2012, 149:923 - 935.
  • 7Saitsu H, Osaka H, Sugiyama S. Early infantile epileptic encepha- lopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2 ( SRGAP2 ) [ J ]. Am J Med Genet A, 2012, 158 : 199 - 205.
  • 8Mason FM, Heimsath EG, Higgs HN, et al. Bi-modal regulation of a formin by srGAP2[J]. J Bid Chem, 2011,286:6577 -6586.
  • 9Guo S, Bao S. srGAP2 arginine methylation regulates cell migration and cell spreading through promoting dimerization [ J ]. Biol Chem, 2010, 28:35133 - 35141.
  • 10Bacon C, Endris V, Rappold G, et al. Dynamic expression of the Slit-Robo GTPase activating protein genes during development of the murine nervous system [ J ]. J Comp Neurel, 2009, 513:224 -236.

引证文献2

二级引证文献1

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部