nrg1erbb4信号在fmr1基因敲除鼠脑组织中改变及意义-change and significance of nrg 1 erbb 4 signal in brain tissue of fm r1 knockout mice.docxVIP

KO2w 和 KO4w 小鼠大脑皮质 NRG1、ErbB4 含量分别较 WT2w 和 WT4w 小鼠减少，差异有 统计学意义；KO2w 和 KO4w 小鼠海马中 NRG1、ErbB4 含量分别较 WT2w 和 WT4w 小鼠减少， 差异有统计学意义。4. KO 与 WT 小鼠脑组织 PV 阳性神经元 ErbB4 表达量的比较KO2w 和 KO4w 小鼠皮质、海马 CA1 及 CA3 区 PV 与 ErbB4 共标记的神经元上，共定 位阳性神经元均较 WT2w 和 WT4w 小鼠减少，差异有统计学意义；而海马齿状回区 PV 与 ErbB4 共表达的神经元与同龄小鼠相比差异无统计学意义。结论：KO2w 和 KO4w 小鼠大脑皮质及海马 NRG1、ErbB4 阳性神经元数量、NRG1、ErbB4 表 达量以及 PV 阳性神经元 ErbB4 表达量均减少，提示 NRG1-ErbB4 信号的降低可能与 KO 小鼠 PV 阳性 GABA 能中间神经元的减少有关，可能在 FXS 癫痫易感性增高中发挥 重要作用。【关键词】脆性 X 综合征；抑制性中间神经元； 脑组织；神经调节蛋白 1；ErbB4The changes and significances of NRG1-ErbB4 signal in brain tissues of Fmr1 knockout micePostgraduate: TAO LU Advisor: Prof. Yonghong YiAbstractThe fragile X syndrome is the most frequent form of inherited mental retardation in humans, with an incidence of 1 in 4000 males and 1 in 8000 females.The molecular basis for this disease is the unstable amplified of a triplet repeat (CGG),in the 5’ untranslated region and abnormal methylation of cytosine nucleotides of fragile X mental retardation gene (FMR1), resulting in gene transcriptional silence and gene product fragile X mental retardation protein (FMRP) reduced or missing.The main clinical manifestations include varying degrees of mental retardation, attention deficit hyperactivity and autism, 20%-25% of patients suffered from epilepsy.Recent studies has shown that the hypofunction of the inhibitory interneurons leads to enhanced excitability in cerebral cortex have linked to the pathogenesis in FXS.We also found the reduced number of GAD and PV positive neurons , as well as decreased current density of type I voltage-gated sodium channel (Nav1.1) on interneuron in Fmr1 knockout mice.Our research group also found the area of PV cells reduce in cortex, temporal cortex, piriform cortex compared to the age-match WT mice in 2 weeks Fmr1 KO mice. There is significant increased in CA2,CA3, striate cortex ,temporal auditory cortex and piriform cortex in KO4w mice comparedwith WT4w.And Our research group also found GABAAR α 5 protein ex