Differential expression patterns of chloride transporters, Na+-K+-2Cl--cotransporter and K+-Cl--cotransporter, in epilepsy-associated malformations of cortical development
Differential expression patterns of chloride transporters, Na+-K+-2Cl--cotransporter and K+-Cl--cotransporter, in epilepsy-associated malformations of cortical development
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DOI：
10.1016/j.neuroscience.2006.11.041
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发表时间：
2007-03-02
期刊：
影响因子：
3.3
通讯作者：
Gorter, J. A.
中科院分区：
文献类型：
--
作者：
Aronica, E.;Boer, K.;Gorter, J. A.
皮质发育畸形是公认的慢性药物难治性癫痫的原因。越来越多的观察表明，阳离子-氯离子共转运蛋白（CCT）在控制神经元功能中的重要作用。其表达的失调可能有助于导致癫痫发作的过度兴奋机制。在本研究中，Na+-K+-2Cl（-）-协同转运蛋白（NKCC 1）和K+-Cl-协同转运蛋白（KCC 2）的表达和细胞特异性分布在不同的发育病变，包括局灶性皮质发育不良（FCD）IIB型（n=9），半侧巨脑畸形（HMEG，n=6）和神经节细胞胶质瘤（GG，n=9）从药物难治性癫痫患者和年龄匹配的对照。在正常对照成人皮质中，NKCC 1显示低神经元和胶质细胞表达水平。相比之下，KCC 2显示出强烈且弥漫的神经毡染色。KCC 2未发现显著的神经胶质免疫反应性（IR）。NKCC 1在大多数FCD、HMEG和GG标本中高度表达。在不同大小的神经元中观察到NKCC 1 IR，包括大的发育不良神经元、气球细胞（在FCD和HMEG病例中）和具有星形胶质细胞形态的神经胶质细胞。与对照组相比，FCD、HMEG和GG标本中KCC 2的免疫反应模式的特征在于神经元染色较少，而体内IR较多。KCC 2 IR在不同大小的神经元中观察到，包括大型发育不良的神经元，但在气球细胞或星形胶质细胞形态的胶质细胞中没有观察到。双标记实验证实了两种CCT的差异细胞分布及其在GABA（A）受体（α 1亚基）阳性发育不良神经元中的表达。CCT的细胞分布，NKCC 1在发育不良的神经元中的高表达和KCC 2的亚细胞分布的改变类似于未成熟的皮质，并表明CCT对皮质发育畸形的高致癫痫性的可能贡献。(c)2006年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Malformations of cortical development are recognized causes of chronic medically intractable epilepsy. An increasing number of observations suggests an important role for cation-chloride co-transporters (CCTs) in controlling neuronal function. Deregulation of their expression may contribute to the mechanisms of hyperexcitability that lead to seizures. In the present study the expression and cell-specific distribution of Na+-K+-2Cl(-)-cotransporter (NKCC1) and K+-Cl--cotransporter (KCC2) were studied immunocytochemically in different developmental lesions, including focal cortical dysplasia (FCD) type IIB (n=9), hemimegalencephaly (HMEG, n=6) and ganglioglioma (GG, n=9) from patients with medically intractable epilepsy and in age-matched controls. In normal control adult cortex, NKCC1 displayed low neuronal and glial expression levels. In contrast KCC2 showed strong and diffuse neuropil staining. Notable glial immunoreactivity (IR) was not found for KCC2. NKCC1 was highly expressed in the majority of FCD, HMEG and GG specimens. NKCC1 IR was observed in neurons of different size, including large dysplastic neurons, in balloon cells (in FCD and HMEG cases) and in glial cells with astrocytic morphology. The immunoreactivity pattern of KCC2 in FCD, HMEG and GG specimens was characterized by less neuropil staining and more intrasomatic IR compared with control. KCC2 IR was observed in neurons of different size, including large dysplastic neurons, but not in balloon cells or in glial cells with astrocytic morphology. Double-labeling experiments confirmed the differential cellular distribution of the two CCTs and their expression in GABA(A) receptor (alpha 1 subunit)-positive dysplastic neurons. The cellular distribution of CCTs, with high expression of NKCC1 in dysplastic neurons and altered subcellular distribution of KCC2 resembles that of immature cortex and suggests a possible contribution of CCTs to the high epileptogenicity of malformations of cortical development. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.