mGluR5拮抗剂对FMR1基因敲除小鼠树突棘的影响及其机制探讨  

Effect of mGluR5 Antagonist on Dendritic Spines in FMR1-knockout Mice and Its Underlying Mechanism

作　　者：范红星[1] 易咏红[1] 孙卫文[1] 徐琳[1] 廖卫平[1] 

机构地区：[1]广州医学院神经科学研究所广州医学院第二附属医院神经内科,广东广州510260

出　　处：《广州医学院学报》2007年第1期6-9,共4页Academic Journal of Guangzhou Medical College

基　　金：国家自然科学基金项目(30370504);广东省自然科学基金重点项目(04105429)

摘　　要：目的:探讨代谢性谷氨酸受体5(mGluR5)拮抗剂2-甲基-6-苯基乙炔嘧啶(MPEP)对脆性X综合征树突棘发育的影响及其机制。方法:新生FMR1基因敲除(KO)小鼠腹腔注射MPEP1次、1周,以同龄KO鼠和野生鼠(WT)注射生理盐水对照。免疫印迹法检测微管相关蛋白1B(MAP1B)含量改变,并以单片Golgi染色方法观察皮质感觉区第Ⅴ层锥体神经元树突棘长度和密度。结果:KO小鼠树突棘长度和密度都显著高于WT小鼠,MAP1B含量也明显增高。MPEP干预1周MAP1B表达显著减少,树突棘长度、密度明显降低。MPEP1次干预明显减少MAP1B,对树突棘无影响。结论:脆性X综合征树突棘的发育异常与mGluR5信号的过度激活有关,MAP1B的过表达可能是主要环节。　Objective：To investigate the effect of MPEP,an antagonist of the metabotropic glutamate receptor 5（mGluR5）,on development of dendritic spines in FMR1-knockout mice.Methods：Single dose of MPEP were administered intraperitoneally into neonatal FMR1-knockout mice,while FMR1-knockout and wild type control mice were injected intraperitoneally with normal saline.Subsequently,western blotting was used to determine the level of MAP1B and single-section Golgi-Cox technique was used to examine the length and density of spines of layer V neurons in the somatosensory cortex.Results：FMR1-knockout mice exhibited significantly more and longer dendritic spines than wild type mice.In addition,the expression of MAP1B was more intensive in FMR1-knockout mice than in control mice.MPEP reduced the mean length and density of spines,and the level of MAP1B after 1-week treatment in FMR1-knockout mice.MPEP significantly decreased expression of MAP1B,but had no effect on spines after single dosage.Conclusion：The developmental defects of dendritic spines in fragile X syndrome may result from overactive mGluR5 signaling in FMR1-knockout mice,in which the over-expression of MAP1B may be playing a primary role.

关 键 词：脆性X综合征 树突棘 代谢性谷氨酸受体5 2-甲基-6-苯基乙炔嘧啶 微管相关蛋白1B 小鼠 

分 类 号：R965[医药卫生—药理学]