颞叶癫痫新生海马齿状回颗粒细胞增殖发育的克隆性分析
Clonal analysis of newborn hippocampal dentate granule cell proliferation and development in temporal lobe epilepsy
摘要：
海马齿状核颗粒细胞是哺乳动物在整个成年生活中产生的少数神经元细胞类型之一。在正常的大脑中，新的颗粒细胞从颗粒下区的祖细胞产生，并以典型的方式整合。在癫痫的发展过程中，颗粒细胞整合发生了深刻的变化。新细胞迁移到异位位置并发育出定向错误的基底树突。虽然已经确定这些异常细胞是新产生的，但尚不清楚它们是否在整个祖细胞库中普遍存在，或者来源于较少数量的不良行为祖细胞。为了探讨这个问题，我们进行了一项克隆分析研究，在小鼠表达的Brainbow荧光蛋白报告构建在齿状颗粒细胞祖细胞。在匹鲁卡品诱导癫痫持续状态（导致癫痫发展的治疗）后2个月检查小鼠。使脑切片呈半透明，以便可以重建整个脑嵴，并鉴定所有荧光标记的细胞。我们的研究结果表明，少数祖细胞产生的异位细胞的癫痫持续状态后，大多数，这表明无论是受影响的祖细胞或其局部微环境已成为病理。与此相反，颗粒细胞与基底树突均匀分布在克隆组。这表明这些祖细胞可以产生正常细胞，并表明全局因子偶尔破坏一些新细胞的树突发育。总之，这些发现有力地预测了不同的机制调节不同的方面，
英文摘要：
Hippocampal dentate granule cells are among the few neuronal cell types generated throughout adult life in mammals. In the normal brain, new granule cells are generated from progenitors in the subgranular zone and integrate in a typical fashion. During the development of epilepsy, granule cell integration is profoundly altered. The new cells migrate to ectopic locations and develop misoriented basal dendrites. Although it has been established that these abnormal cells are newly generated, it is not known whether they arise ubiquitously throughout the progenitor cell pool or are derived from a smaller number of bad actor progenitors. To explore this question, we conducted a clonal analysis study in mice expressing the Brainbow fluorescent protein reporter construct in dentate granule cell progenitors. Mice were examined 2 months after pilocarpine-induced status epilepticus, a treatment that leads to the development of epilepsy. Brain sections were rendered translucent so that entire hippocampi could be reconstructed and all fluorescently labeled cells identified. Our findings reveal that a small number of progenitors produce the majority of ectopic cells following status epilepticus, indicating that either the affected progenitors or their local microenvironments have become pathological. By contrast, granule cells with basal dendrites were equally distributed among clonal groups. This indicates that these progenitors can produce normal cells and suggests that global factors sporadically disrupt the dendritic development of some new cells. Together, these findings strongly predict that distinct mechanisms regulate different aspects
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