Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Molecular and Developmental Biology Graduate Program, University of Cincinnati, Cincinnati, Ohio.
Hippocampus. 2013 Dec;23(12):1309-20. doi: 10.1002/hipo.22169. Epub 2013 Aug 26.
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 1 day or 1 month after the last evoked seizure. Interestingly, significant reductions in dendritic spine density were evident 1 day after the last seizure, the magnitude of which had diminished by 1 month. Further, there was an increase in the thickness of the granule cell layer 1 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.
颞叶癫痫与海马齿状回颗粒细胞形态的变化有关。这些变化在许多与大量神经元丢失和自发性复发性癫痫相关的模型中是明显的。相比之下，先前的研究表明，在点燃模型中，有可能给予有限数量的刺激，足以产生终生增强对刺激诱发癫痫的敏感性，而没有相关的自发性癫痫和最小的神经元丢失。在这里，我们研究了是否刺激杏仁核足以引起五次惊厥性发作（Racine 量表的 IV 级或更高），是否会产生类似于与大量细胞丢失相关的癫痫模型中观察到的形态变化。在最后一次诱发的癫痫发作后 1 天或 1 个月，检查了来自 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 1 天，树突棘密度明显降低，1 个月后降低幅度减小。此外，最后一次诱发的癫痫发作后 1 天，颗粒细胞层的厚度增加，一个月后则没有。我们还观察到近端轴突面积增加，一个月后又恢复到对照水平。在任何时间点都没有检测到基底树突数量的差异。这些发现表明，点燃癫痫发生的早期阶段会导致颗粒细胞体层厚度、分子层棘突密度和轴突近端区域的短暂变化，但不会导致颗粒细胞结构的明显重排。
