Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice
Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice
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DOI：
10.1093/jnen/64.6.537
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发表时间：
2005-06-01
影响因子：
3.2
通讯作者：
Goto, Y
中科院分区：
文献类型：
--
作者：
Fukuda, T;Itoh, M;Goto, Y
我们检测到Mecp 2-半合子（Mecp 2（-/y））小鼠大脑皮层的形态异常。与野生型雄性小鼠相比，突变体小鼠的体感和运动皮质的皮质厚度在4周龄后没有增加。MecP 2（-/y）小鼠的II/III层和V层中这些区域的神经元密度显著高于野生型小鼠，特别是在4周龄后的II/III层中。在Mecp 2（-/y）小鼠的体感皮层的II/III层中，顶树突的直径较细，树突棘的数量较少。电子显微镜显示，两周大的突变体已经有许多过早的突触后密度。这些结果表明，Mecp 2（-/y）小鼠大脑皮层的神经元成熟延迟，并且最初的神经元变化是由过早的突触发生引起的。具有Mecp 2杂合突变的Rett综合征患者表现出发育障碍，包括皮质功能障碍，如精神发育迟滞、自闭症和癫痫。我们的研究结果提供了证据的相似性Rett综合征的大脑在某些方面，并建议MeCP 2/Mecp 2在突触发生中发挥一定的作用。
We detected morphologic abnormalities in the cerebral cortex of Mecp2-hemizygous (Mecp2(-/y)) mice. The cortical thickness of both somatosensory and motor cortices in mutants did not increase after 4 weeks of age, as compared with that in wild-type male mice. The density of neurons in those areas was significantly higher in layers II/III and V of MecP2(-/y) mice than in wild-type mice, particularly in layers II/III after 4 weeks of age. In layer II/III of the somatosensory cortex of Mecp2(-/y) mice, the diameter of the apical dendrite was thin and the number of dendritic spines was small. Electron microscopy revealed that two-week-old mutants already bad numerous premature postsynaptic densities. These results indicate that Mecp2(-/y) mice suffered delayed neuronal maturation of the cerebral cortex and that the initial neuronal changes were caused by premature synapto-genesis. Rett syndrome patients with a heterozygous mutation of Mecp2 display developmental disorders including cortical malfunctions such as mental retardation, autism, and epilepsy. Our results provide evidence of the similarity with Rett syndrome brains in some respects and suggest that MeCP2/Mecp2 plays some role in synaptogenesis.