Widespread Changes in Dendritic and Axonal Morphology in Mecp2-Mutant Mouse Models of Rett Syndrome: Evidence for Disruption of Neuronal Networks
Widespread Changes in Dendritic and Axonal Morphology in Mecp2-Mutant Mouse Models of Rett Syndrome: Evidence for Disruption of Neuronal Networks
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DOI：
10.1002/cne.22009
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发表时间：
2009-05-20
影响因子：
2.5
通讯作者：
Francke, Uta
中科院分区：
文献类型：
--
作者：
Belichenko, Pavel V.;Wright, Elena E.;Francke, Uta
Rett综合征（RTT）是一种由X连锁基因MECP 2突变引起的神经发育障碍。患有RTT的女孩显示出大脑功能的巨大变化，但相对较少的研究探索了神经回路的结构。检查RTT的两个小鼠模型（Mecp 2B和Mecp 2 J），我们以前记录了大脑解剖结构的变化。在此，我们使用共聚焦显微镜研究MeCP 2缺乏对齿状筋膜（FD），海马CA 1区和运动皮层的树突和轴突的形态学的影响，荧光黄显微注射或碳菁染料示踪。在3周龄时，Mecp 2B小鼠中的大多数（41个中的33个）形态学参数显著改变; Mecp 2 J小鼠中较少（39个中的23个）异常。树突棘的密度和大小以及轴突的密度和方向发生了显著变化。在Mecp 2B小鼠中，FD（类似于11%）、CA 1（14-22%）和运动皮质（类似于16%）中的树突棘密度降低。在Mecp 2B FD中发现脊柱头部尺寸减小（类似于9%）和脊柱颈部长度增加（类似于12%）。此外，运动皮层的轴突也是紊乱的。在Mecp 2 J小鼠中，CA 1的脊柱密度显着降低（14-26%）。在两种模型中，在研究的所有区域均观察到树突状肿胀和伸长的棘颈。在相邻神经元的树突中注意到变化的类型和程度的显著变化。电子显微镜证实异常树突和轴突，并显示异常线粒体。我们的研究结果记录了广泛的树突和轴突的异常，概括了RTT中看到的异常。神经学比较杂志514：240-258，2009. (C)2009威利-利斯公司
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked gene MECP2. Girls with RTT show dramatic changes in brain function, but relatively few studies have explored the structure of neural circuits. Examining two mouse models of RTT (Mecp2B and Mecp2J), we previously documented changes in brain anatomy. Herein, we use con-focal microscopy to study the effects of MeCP2 deficiency on the morphology of dendrites and axons in the fascia dentata (FD), CA1 area of hippocampus, and motor cortex following Lucifer yellow microinjection or carbocyanine dye tracing. At 3 weeks of age, most (33 of 41) morphological parameters were significantly altered in Mecp2B mice; fewer (23 of 39) were abnormal in Mecp2J mice. There were striking changes in the density and size of the dendritic spines and density and orientation of axons. In Mecp2B mice, dendritic spine density was decreased in the FD (similar to 11%), CA1 (14-22%), and motor cortex (similar to 16%). A decreased spine head size (similar to 9%) and an increased spine neck length (similar to 12%) were found in Mecp2B FD. In addition, axons in the motor cortex were disorganized. In Mecp2J mice, spine density was significantly decreased in CA1 (14-26%). In both models, dendritic swelling and elongated spine necks were seen in all areas studied. Marked variation in the type and extent of changes was noted in dendrites of adjacent neurons. Electron microscopy confirmed abnormalities in dendrites and axons and showed abnormal mitochondria. Our findings document widespread abnormalities of dendrites and axons that recapitulate those seen in RTT. J. Comp. Neurol. 514:240-258, 2009. (C) 2009 Wiley-Liss, Inc.