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Comparison of slow and fast neocortical neuron migration using a new in vitro model

机译:使用新的体外模型比较新皮层神经元的慢速和快速迁移

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Background Mutations, toxic insults and radiation exposure are known to slow or arrest the migration of cortical neurons, in most cases by unknown mechanisms. The movement of migrating neurons is saltatory, reflecting the intermittent movement of the nucleus (nucleokinesis) within the confines of the plasma membrane. Each nucleokinetic movement is analogous to a step. Thus, average migration speed could be reduced by lowering step frequency and/or step distance. Results To assess the kinetic features of cortical neuron migration we developed a cell culture system that supports fiber-guided migration. In this system, the majority of fiber-apposed cells were neurons, expressed age-appropriate cortical-layer specific markers and migrated during a 30 min imaging period. Comparison of the slowest and fastest quartiles of cells revealed a 5-fold difference in average speed. The major determinant of average speed in slower cells (6–26 μm/hr) was step frequency, while step distance was the critical determinant of average speed in faster cells (>26 μm/hr). Surprisingly, step distance was largely determined by the average duration of the step, rather than the speed of nucleokinesis during the step, which differed by only 1.3-fold between the slowest and fastest quartiles. Conclusion Saltatory event frequency and duration, not nucleokinetic speed, are the major determinants of average migration speed in healthy neurons. Alteration of either saltatory event frequency or duration should be considered along with nucleokinetic abnormalities as possible contributors to pathological conditions.
机译:背景技术已知,在大多数情况下,通过未知机制,突变,毒性侮辱和辐射暴露会减缓或阻止皮质神经元的迁移。迁移的神经元的运动是咸的,反映了质膜范围内核的间歇性运动(核分裂)。每个核动力学运动都类似于一个步骤。因此,可以通过降低步进频率和/或步进距离来降低平均迁移速度。结果为了评估皮质神经元迁移的动力学特征,我们开发了一种支持纤维引导的迁移的细胞培养系统。在该系统中,大多数纤维附着的细胞是神经元,表达适合年龄的皮质层特异性标记,并在30分钟的成像期间迁移。比较最慢和最快的四分位数的细胞,发现平均速度相差5倍。较慢电池的平均速度(6-26μm/ hr)的主要决定因素是步频,而步距是较快电池的平均速度(> 26μm/ hr)的关键决定因素。令人惊讶的是,步距很大程度上取决于步的平均持续时间,而不是步中的核分裂速度,最慢和最快四分位数之间的差异仅为1.3倍。结论盐碱化事件的频率和持续时间,而不是核动力学速度,是健康神经元平均迁移速度的主要决定因素。应考虑盐变事件频率或持续时间的改变以及核动力学异常,这可能是导致病理状况的原因。

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