Granule cell dispersion is not accompanied by enhanced neurogenesis in temporal lobe epilepsy patients
Granule cell dispersion is not accompanied by enhanced neurogenesis in temporal lobe epilepsy patients
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DOI：
10.1016/j.expneurol.2006.08.023
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发表时间：
2007-02-01
影响因子：
5.3
通讯作者：
Haas, Carola A.
中科院分区：
文献类型：
--
作者：
Fahrner, Alexander;Kann, Gunda;Haas, Carola A.
齿状回中的颗粒细胞分散 (GCD) 是阿蒙角硬化症 (AHS) 的常见特征，通常与颞叶癫痫 (TLE) 相关。据推测，GCD 可能是由新生颗粒细胞的异常迁移引起的。为了检验这一假设，我们在手术切除的 TLE 患者和对照海马中使用了增殖和神经发生标记物、免疫细胞化学方法以及定量蛋白质印迹和实时 RT-PCR 分析。 1 岁以下时，在 TLE 患者的齿状回颗粒下区中检测到 Ki-67 免疫阳性细胞核，但在 TLE 患者的齿状中未检测到，与年龄无关。在对照组和 TLE 患者中，增殖标志物微型染色体维持蛋白 2 (mcm2) 和双皮质素 (DCX) 的表达随着年龄的增长而显着下降，但这两种蛋白的表达与 AHS 和 GCD 的程度无关。定量实时 RT-PCR 在基因表达水平上证实了这些发现。相比之下，神经胶质原纤维酸性蛋白 (GFAP) 和波形蛋白的免疫细胞化学以及高尔基体染色显示 GCD 区域呈放射状排列的神经胶质网络。 GFAP阳性纤维长度随着GCD的严重程度显着增加。这些结果表明，癫痫活动不会刺激人类齿状回的神经发生，并且 GCD 可能不是由新生成的颗粒细胞的错位引起的，而是由成熟颗粒细胞沿着放射状胶质支架的异常迁移引起的。 (c) 2006 Elsevier Inc. 保留所有权利。
Granule cell dispersion (GCD) in the dentate gyrus is a frequent feature of Ammon's horn sclerosis (AHS) which is often associated with temporal lobe epilepsy (TLE). It has been hypothesized that GCD may be caused by an abnormal migration of newly born granule cells. To test this hypothesis, we used markers of proliferation and neurogenesis and immunocytochemical methods as well as quantitative Western blot and real-time' RT-PCR analyses, in surgically resected hippocampi from TLE patients and controls. Below the age of 1 year, Ki-67-immunopositive nuclei were detected in the subgranular zone of the dentate gyrus, but not in the dentate of TLE patients independent of age. The expression of the proliferation marker minichromosome maintenance protein 2 (mcm2) and of doublecortin (DCX) decreased significantly with age in controls and in TLE patients, but the expression of both proteins was independent of the degree of AHS and GCD. Quantitative real-time RT-PCR confirmed these findings at the level of gene expression. In contrast, immumocytochemistry for glial fibrillary acidic protein (GFAP) and vimentin as well as Golgi staining revealed a radially aligned glial network in the region of GCD. GFAP-positive fiber length significantly increased with the severity of GCD. These results indicate that epileptic activity does not stimulate neurogenesis in the human dentate gyrus and that GCD probably does not result from a malpositioning of newly generated granule cells, but rather from an abnormal migration of mature granule cells along a radial glial scaffold. (c) 2006 Elsevier Inc. All rights reserved.