Doublecortin-like (DCL) expression in focal cortical dysplasia and cortical tubers
Doublecortin-like (DCL) expression in focal cortical dysplasia and cortical tubers
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DOI：
10.1111/j.1528-1167.2009.02191.x
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发表时间：
2009-12-01
期刊：
影响因子：
5.6
通讯作者：
Aronica, Eleonora
中科院分区：
文献类型：
--
作者：
Boer, Karin;Lucassen, Paul J.;Aronica, Eleonora
P>目的：IIB 型局灶性皮质发育不良 (FCD IIB) 和结节性硬化症 (TSC) 患者的皮质结节是皮质发育畸形，常与难治性癫痫相关。它们的组织病理学和分子特征表明皮质发育早期阶段的发育异常，这可能涉及神经祖细胞。我们研究的目的是确定 FCD 和 TSC 中双皮质素样 (DCL) 的表达和细胞特异性分布，DCL 是一种在早期皮质发生过程中关键参与神经元分裂和径向迁移的蛋白质。方法：使用免疫细胞化学、共聚焦分析和蛋白质印迹法，在 FCD IIB (n = 8) 和 TSC（皮质结节；n = 8）癫痫手术病例中研究 DCL。 结果：尸检和手术控制新皮质样本的特征是所有皮质层都有适度的 DCL 免疫反应性 (IR)，但在白质中未检测到 DCL IR。 FCD 中的球囊细胞 (BC) 和 TSC 中的巨细胞 (GC) 表达强 DCL IR。 FCD 和 TSC 中大多数大型发育不良神经元 (DN) 均呈 DCL 阳性。在 FCD 和 TSC 标本中均观察到 DCL 与神经祖细胞或神经母细胞标记物巢蛋白、GFAP δ 和双皮质素的共表达。通过蛋白质印迹分析证实，与对照皮质相比，发育不良皮质内的 DCL 表达增加。讨论：FCD 和 TSC 中 BC/GC 和 DN 出生后显着表达 DCL，支持这种微管相关蛋白在早期人类皮质发育过程中的重要作用，这可能与这些发育性胶质神经元畸形的发病机制有关。
P>Purpose:Focal cortical dysplasia type IIB (FCD IIB) and cortical tubers of patients with tuberous sclerosis complex (TSC) are malformations of cortical development that are frequently associated with intractable epilepsy. Their histopathologic and molecular features suggest developmental abnormalities during the early stages of cortical development, which may involve neural progenitor cells. The aim of our study was to define the expression and cell-specific distribution of doublecortin-like (DCL), a protein critically involved in neuronal division and radial migration during early corticogenesis, in both FCD and TSC.Methods:DCL was studied in epilepsy surgery cases with FCD IIB (n = 8) and TSC (cortical tubers; n = 8) using immunocytochemistry, confocal analysis, and Western blotting.Results:Autopsy and surgical control neocortical specimens were characterized by modest DCL immunoreactivity (IR) throughout all cortical layers, but DCL IR was not detectable in the white matter. Balloon cells (BCs) in FCD and giant cells (GCs) in TSC expressed strong DCL IR. Most of the large dysplastic neurons (DNs) were positive for DCL in both FCD and TSC. Coexpression of DCL with the neural progenitor or neuroblast markers nestin, GFAP delta, and doublecortin was observed in both FCD and TSC specimens. The increased DCL expression within the dysplastic cortex, compared to control cortex, was confirmed by Western blot analysis.Discussion:The prominent postnatal expression of DCL by BCs/GCs and DNs in FCD and TSC supports an important role for this microtubule associated protein, also during early human cortical development, which could be relevant to the pathogenesis of these developmental glioneuronal malformations.