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Impaired Cortical Cytoarchitecture and Reduced Excitability of Deep-Layer Neurons in the Offspring of Diabetic Rats
Frontiers in Cell and Developmental Biology ( IF 5.5 ) Pub Date : 2020-08-17 , DOI: 10.3389/fcell.2020.564561
Rocío Valle-Bautista , Berenice Márquez-Valadez , América D. Fragoso-Cabrera , Guadalupe García-López , Néstor Fabián Díaz , Gabriel Herrera-López , Ernesto Griego , Emilio J. Galván , José-Antonio Arias-Montaño , Anayansi Molina-Hernández

Maternal diabetes has been related to low verbal task scores, impaired fine and gross motor skills, and poor performance in graphic and visuospatial tasks during childhood. The primary motor cortex is important for controlling motor functions, and embryos exposed to high glucose show changes in cell proliferation, migration, and differentiation during corticogenesis. However, the existing studies do not discriminate between embryos with or without neural tube defects, making it difficult to conclude whether the reported changes are related to neural tube defects or other anomalies. Furthermore, postnatal effects on central nervous system cytoarchitecture and function have been scarcely addressed. Through molecular, biochemical, morphological, and electrophysiological approaches, we provide evidence of impaired primary motor cerebral cortex lamination and neuronal function in pups from diabetic rats, showing an altered distribution of SATB2, FOXP2, and TBR1, impaired cell migration and polarity, and decreased excitability of deep-layer cortical neurons, suggesting abnormalities in cortico-cortical and extra-cortical innervation. Furthermore, phase-plot analysis of action potentials suggests changes in the activity of potassium channels. These results indicate that high-glucose insult during development promotes complex changes in migration, neurogenesis, cell polarity establishment, and dendritic arborization, which in turn lead to reduced excitability of deep-layer cortical neurons.



中文翻译:

糖尿病大鼠后代的皮质细胞结构受损和深层神经元兴奋性降低

孕产妇糖尿病与口头任务评分低,精细和粗略的运动技能受损以及儿童时期图形和视觉空间任务表现不佳有关。初级运动皮层对于控制运动功能很重要,暴露于高葡萄糖的胚胎在皮质发生过程中显示出细胞增殖,迁移和分化的变化。但是,现有研究没有区分具有或没有神经管缺陷的胚胎,因此很难下结论所报告的变化是否与神经管缺陷或其他异常有关。此外,几乎没有解决产后对中枢神经系统细胞结构和功能的影响。通过分子,生化,形态学和电生理学方法,我们提供了糖尿病大鼠幼犬原发性运动大脑皮层层压和神经元功能受损的证据,表明SATB2,FOXP2和TBR1的分布发生了改变,细胞迁移和极性受损,深层皮层神经元的兴奋性降低,提示皮质皮质和皮质外神经。此外,动作电位的相图分析表明钾通道活性的变化。这些结果表明,发育过程中的高葡萄糖损伤会促进迁移,神经发生,细胞极性建立和树突状乔化的复杂变化,进而导致深层皮层神经元的兴奋性降低。细胞迁移和极性受损,深层皮层神经元兴奋性降低,提示皮层和皮层神经支配异常。此外,动作电位的相图分析表明钾通道活性的变化。这些结果表明,发育过程中的高葡萄糖损伤会促进迁移,神经发生,细胞极性建立和树突状乔化的复杂变化,进而导致深层皮层神经元的兴奋性降低。细胞迁移和极性受损,深层皮层神经元兴奋性降低,提示皮层和皮层神经支配异常。此外,动作电位的相图分析表明钾通道活性的变化。这些结果表明,发育过程中的高葡萄糖损伤会促进迁移,神经发生,细胞极性建立和树突状乔化的复杂变化,进而导致深层皮层神经元的兴奋性降低。

更新日期:2020-09-18
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