Morphological changes among hippocampal dentate granule cells exposed to early kindling-epileptogenesis.

Morphological changes among hippocampal dentate granule cells exposed to early kindling-epileptogenesis.
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DOI:
10.1002/hipo.22169
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发表时间:
2013-12
期刊:
影响因子:
3.5
通讯作者:
Danzer, Steve C.
Danzer, Steve C.
中科院分区:
医学3区
文献类型:
--
作者:
Singh, Shatrunjai P.;He, Xiaoping;McNamara, James O.;Danzer, Steve C.

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颞叶癫痫与海马齿状回颗粒细胞形态学改变相关。这些变化在与大量神经元丢失和自发性复发性癫痫发作相关的许多模型中是明显的。相比之下,以前的研究表明,在点燃模型中,有可能给予有限数量的刺激,足以产生终身增强的敏感性刺激诱发癫痫发作,而没有相关的自发性癫痫发作和最小的神经元损失。在这里,我们研究是否刺激杏仁核足以引起五个惊厥发作(IV级或以上的拉辛的规模)产生形态学的变化与大量细胞丢失相关的癫痫模型中观察到的相似。在最后一次诱发癫痫发作后一天或一个月检查来自Thy-1 GFP小鼠的GFP表达颗粒细胞的形态。有趣的是,最后一次癫痫发作后一天,树枝状棘密度明显降低,其幅度在一个月后就减弱了。此外,在最后一次诱发癫痫发作后一天,颗粒细胞层的厚度增加,一个月后没有。我们还观察到近端轴突面积增加,一个月后再次恢复到对照水平。在任一时间点均未检测到基底树突数量的差异。这些结果表明,点燃癫痫发生的早期阶段产生短暂的颗粒细胞体层厚度,分子层棘密度和轴突近端面积的变化,但不产生显着的颗粒细胞结构的重排。
Temporal lobe epilepsy is associated with changes in the morphology of hippocampal dentate granule cells. These changes are evident in numerous models that are associated with substantial neuron loss and spontaneous recurrent seizures. By contrast, previous studies have shown that in the kindling model, it is possible to administer a limited number of stimulations sufficient to produce a lifelong enhanced sensitivity to stimulus evoked seizures without associated spontaneous seizures and minimal neuronal loss. Here we examined whether stimulation of the amygdala sufficient to evoke five convulsive seizures (class IV or greater on Racine’s scale) produce morphological changes similar to those observed in models of epilepsy associated with substantial cell loss. The morphology of GFP-expressing granule cells from Thy-1 GFP mice was examined either one day or one month after the last evoked seizure. Interestingly, significant reductions in dendritic spine density were evident one day after the last seizure, the magnitude of which had diminished by one month. Further, there was an increase in the thickness of the granule cell layer one day after the last evoked seizure, which was absent a month later. We also observed an increase in the area of the proximal axon, which again returned to control levels a month later. No differences in the number of basal dendrites were detected at either time point. These findings demonstrate that the early stages of kindling epileptogenesis produce transient changes in the granule cell body layer thickness, molecular layer spine density and axon proximal area, but do not produce striking rearrangements of granule cell structure.
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