中文摘要：

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。

英文摘要：

　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.