神经调节蛋白1受体ErbB4在FMR1基因敲除小鼠脑组织中的表达变化及意义  

Changes of neuregulin 1 receptor ErbB4 and their significance in FMR1 gene knockout mouse

作　　者：卢韬[1] 欧阳梅 易咏红[3] 

机构地区：[1]广西医科大学第四附属医院神经内科,柳州545005 [2]广东三九脑科医院神经内科,广州510510 [3]广州医科大学第二附属医院神经科学研究所,广州510260

出　　处：《中华神经医学杂志》2017年第11期1134-1138,共5页Chinese Journal of Neuromedicine

基　　金：广东省自然科学基金重点项目（04105429）

摘　　要：目的探讨神经调节蛋白I（NRGl）受体ErbB4在脆性x智力障碍I（FMRl）基因敲除型（K0）小鼠大脑皮质及海马中的表达变化，从而分析其在脆性x综合征（FXS）癫痫易感性增高的发病机制中的作用。方法取出生后2周、4周雄性FMRJKO小鼠各3只分别设为2周KO组、4周KO组，取同龄雄性野生型（WT）／b鼠各3只分别设为2周WT组、4周wT组。应用免疫组化染色及Westemblotting检测小鼠大脑皮质及海马ErbB4阳性神经元及蛋白的表达，应用免疫荧光双标染色、激光共聚焦显微镜观察小鼠大脑皮质及海马微白蛋白（PVl阳性中间神经元中ErbB4的表达。结果免疫组化染色及Westernblotting检测显示，2周KO组与2周WT组比较、4周KO组与4周wT组相比，小鼠大脑皮质、海马ErbB4阳性神经元数量及蛋白表达量均明显减少，差异均有统计学意义（p〈0．05）。免疫荧光双标染色显示，2周KO组与2周wT组比较、4周K0组与4周wT组相比，小鼠大脑皮质及海马CAl区、CA3区PV与ErbB4共表达神经元数量明显减少，差异均有统计学意义（P〈0．05）。结论ErbB4表达量减少与FMRlKO小鼠PV阳性中间神经元减少有关，其参与了FXS癫痫易感性增高的发病机制。Objective To study the expression changes ofneuregulin 1 （NRGI） receptor ErbB4 in the cortex and hippocampus of fragile X mental retardation 1 （FMR1） gene knockout （KO） mice, and explore the role of ErbB4 in epilepsy susceptibility in fragile X syndrome （FXS）. Methods Two weeks old male FMR1 KO mice （n=3）, 4 weeks old FMR1 KO mice （n=3） and 2 weeks old male wild type （WT） mice （n=3）, 4 weeks old WT mice （n=3） were chosen in our study. Immunohistochemical staining and Western blotting were performed to detect the ErbB4 positive neurons and protein expression in the cerebral cortex and hippocampus of each group. Double-labeling immunofluorescence and laser confocal microscope were used to observe the ErbB4 protein expression in the parvalbumin （PV） inter-neurons of cortex and hippocampus. Results As compared with those in the 2 and 4 weeks old WT mice, the number of ErbB4 positive neurons was significantly smaller and ErbB4 protein expressions in the cerebral cortex and hippocampus of 2 and 4 weeks old KO mice were significantly decreased （P〈0.05）. The number of PV and ErbB4 co-expression neurons in cortex and CA1 and CA3 hippocampus of 2 and 4 weeks old KO mice was significantly smaller than that in the 2 and 4 weeks old WT mice （P〈 0.05）. Conclusion The decreased ErbB4 expression is related to the decreased number of PV positive inter-neurons in the FMR1 KO mice, which is involved in the pathogenesis of FXS epilepsy susceptibility.

关 键 词：脆性X综合征 ERBB4 中间神经元 微白蛋白 癫痫 

分 类 号：R749[医药卫生—神经病学与精神病学]