Fmr1 KO and fenobam treatment differentially impact distinct synapse populations of mouse neocortex.
Fmr1 KO and fenobam treatment differentially impact distinct synapse populations of mouse neocortex.
复制标题
Fmr1 KO 和非诺班治疗对小鼠新皮质的不同突触群产生不同的影响。
DOI：
10.1016/j.neuron.2014.11.016
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发表时间：
2014
期刊：
影响因子：
16.2
通讯作者：
Mourrain,Philippe
中科院分区：
文献类型：
--
作者：
Wang,GordonX;Smith,StephenJ;Mourrain,Philippe
脆性X综合征（FXS）的认知缺陷归因于大脑大量异质性突触群的分子异常。不幸的是，突触的密度加上它们的分子异质性，在理解FXS中突触变化的具体贡献方面提出了巨大的挑战。我们展示了强大的新方法的大规模分子分析的单个突触，允许量化的突触群体中存在的FXS小鼠模型的皮质中的许多特定的变化。对近100万个突触的分析揭示了分布在6,000多个成对度量中的突触蛋白的明显的定量变化。这些突触改变中的一些，但不是全部，通过用候选治疗剂非诺班（一种mGluR 5拮抗剂）治疗而逆转。这些模式的广泛，但不同的突触蛋白的变化，以响应全球扰动表明，FXS及其治疗必须被理解为一个网络系统在突触水平。
Cognitive deficits in fragile X syndrome (FXS) are attributed to molecular abnormalities of the brain's vast and heterogeneous synapse populations. Unfortunately, the density of synapses coupled with their molecular heterogeneity presents formidable challenges in understanding the specific contribution of synapse changes in FXS. We demonstrate powerful new methods for the large-scale molecular analysis of individual synapses that allow quantification of numerous specific changes in synapse populations present in the cortex of a mouse model of FXS. Analysis of nearly a million individual synapses reveals distinct, quantitative changes in synaptic proteins distributed across over 6,000 pairwise metrics. Some, but not all, of these synaptic alterations are reversed by treatment with the candidate therapeutic fenobam, an mGluR5 antagonist. These patterns of widespread, but diverse synaptic protein changes in response to global perturbation suggest that FXS and its treatment must be understood as a networked system at the synapse level.