A novel structure associated with aging is augmented in the DPP6-KO mouse brain.
A novel structure associated with aging is augmented in the DPP6-KO mouse brain.
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DOI：
10.1186/s40478-020-01065-7
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发表时间：
2020-11-23
影响因子：
7.1
通讯作者：
Hoffman DA
中科院分区：
文献类型：
--
作者：
Lin L;Petralia RS;Lake R;Wang YX;Hoffman DA
除了作为A型电压门控K+通道的辅助亚单位外，我们已经报道了单一跨膜蛋白DPP6(DPP6)影响神经元和突触的发育。DPP6-KO小鼠在海马区依赖的学习和记忆方面受到损害，并且表现出较小的脑体积。使用免疫荧光和电子显微镜，我们在这里报告了在海马区CA1区的一个新的结构，与同龄的WT小鼠相比，在老年DPP6-KO小鼠中显著更常见，并且这些结构在DPP6-KO小鼠中被观察到更早的发育。这些新结构以大斑点的形式出现，与NeuN、突触素和嗜铬粒蛋白A共定位，它们还部分标记了MAP2，并在其外围标记了突触素-1和VGluT1。电子显微镜显示，这些结构是异常的、扩大的突触前肿胀，主要充满纤维物质，偶尔有外围突触前活动区形成突触。然后，免疫荧光成像显示，与WT相比，在老年DPP6-KO小鼠的这些新结构中，发现了一些衰老尤其是阿尔茨海默病的标志物水平更高。总之，这些结果表明，衰老的DPP6-KO小鼠具有与阿尔茨海默病的几个标志物相关的新的、异常的突触前结构的数量增加。
In addition to its role as an auxiliary subunit of A-type voltage-gated K+ channels, we have previously reported that the single transmembrane protein Dipeptidyl Peptidase Like 6 (DPP6) impacts neuronal and synaptic development. DPP6-KO mice are impaired in hippocampal-dependent learning and memory and exhibit smaller brain size. Using immunofluorescence and electron microscopy, we report here a novel structure in hippocampal area CA1 that was significantly more prevalent in aging DPP6-KO mice compared to WT mice of the same age and that these structures were observed earlier in development in DPP6-KO mice. These novel structures appeared as clusters of large puncta that colocalized NeuN, synaptophysin, and chromogranin A. They also partially labeled for MAP2, and with synapsin-1 and VGluT1 labeling on their periphery. Electron microscopy revealed that these structures are abnormal, enlarged presynaptic swellings filled with mainly fibrous material with occasional peripheral, presynaptic active zones forming synapses. Immunofluorescence imaging then showed that a number of markers for aging and especially Alzheimer’s disease were found as higher levels in these novel structures in aging DPP6-KO mice compared to WT. Together these results indicate that aging DPP6-KO mice have increased numbers of novel, abnormal presynaptic structures associated with several markers of Alzheimer’s disease.
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影响因子：
3.9
作者：
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通讯作者：
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影响因子：
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通讯作者：
De Klippel, Nina