Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome
Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome
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DOI：
10.1016/j.nbd.2005.07.005
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发表时间：
2006-01-01
影响因子：
6.1
通讯作者：
Fitzsimonds, RM
中科院分区：
文献类型：
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作者：
Asaka, Y;Jugloff, DGM;Fitzsimonds, RM
瑞特综合征是一种由编码转录抑制因子甲基-CpG结合蛋白2（MeCP2）的基因突变引起的X连锁神经发育障碍。在此我们证明，瑞特综合征的Meep2基因敲除小鼠模型在由强直刺激或θ节律刺激诱导的海马CA1区长时程增强方面表现出年龄依赖性损伤。在有行为症状的Mecp2基因敲除小鼠中，重复低频刺激诱导的长时程抑制也不存在。对有行为症状的Meep2基因敲除小鼠进行的免疫印迹分析显示，N -甲基-D -天冬氨酸受体亚单位NR2A和NR2B的表达发生改变。突触前功能也受到影响，这表现为双脉冲易化作用显著降低。有趣的是，Meep2基因敲除小鼠的基础神经传递特性正常，这与我们观察到的包括谷氨酸受体亚单位GluR1和GluR2、PSD95、突触素 - 1、小突触泡蛋白 - 2、突触结合蛋白 - 1、微管相关蛋白2、βIII - 微管蛋白和神经丝蛋白200在内的突触和细胞骨架蛋白的表达水平没有显著改变是一致的。总之，这些数据首次证明Meep2表达缺失伴随着兴奋性突触可塑性的年龄依赖性改变，这可能导致瑞特综合征潜在的认知和功能缺陷。（c）2005年爱思唯尔公司。保留所有权利。
Rett syndrome is an X-linked neurodevelopmental disorder caused by mutations in the gene encoding the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2). Here we demonstrate that the Meep2-null mouse model of Rett syndrome shows an age-dependent impairment in hippocampal CA1 long-term potentiation induced by tetanic or theta-burst stimulation. Long-term depression induced by repetitive low-frequency stimulation is also absent in behaviorally symptomatic Mecp2-null mice. Immunoblot analyses from behaviorally symptomatic Meep2-null mice reveal altered expression of N-methyl-D-aspartate receptor subunits NR2A and NR2B. Presynaptic function is also affected, as demonstrated by a significant reduction in paired-pulse facilitation. Interestingly, the properties of basal neurotransmission are normal in the Meep2-null mice, consistent with our observations that the levels of expression of synaptic and cytoskeletal proteins, including glutamate receptor subunits GluR1 and GluR2, PSD95, synaptophysin-1, synaptobrevin-2, synaptotagmin-1, MAP2, beta III-tubulin and NF200, are not significantly altered. Together, these data provide the first evidence that the loss of Meep2 expression is accompanied by age-dependent alterations in excitatory synaptic plasticity that are likely to contribute to the cognitive and functional deficits underlying Rett syndrome. (c) 2005 Elsevier Inc. All rights reserved.