Dysregulation of sodium channel expression in cortical neurons in a rodent model of absence epilepsy
Dysregulation of sodium channel expression in cortical neurons in a rodent model of absence epilepsy
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DOI：
10.1016/j.brainres.2003.11.051
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发表时间：
2004-03-12
期刊：
影响因子：
2.9
通讯作者：
Blumenfeld, H
中科院分区：
文献类型：
--
作者：
Klein, JP;Khera, DS;Blumenfeld, H
由于皮质神经元参与棘波放电 (SWD) 启动，以及电压门控钠通道 (VGSC) 对神经元放电的贡献，我们检测了 WAG/Rij 缺失癫痫大鼠皮质神经元中 VGSC mRNA 和蛋白质表达的变化。将 WAG/Rij 大鼠与年龄匹配的 Wistar 对照大鼠在 2、4 和 6 个月时进行比较。 VGSC mRNA（通过定量 PCR）和蛋白质（通过免疫细胞化学）的连续 EEG 数据。 WAG/Rij 大鼠的 SWD 随着年龄的增长而增加。发现钠通道 Nav 1.1 和 Nav 1.6（而非 Nav 1.2）的 mRNA 水平在面部体感皮层（AP + 0.0，ML + 6.0 mm）内选择性上调。该皮质区域的 II-IV 层皮质神经元中 Nav 1.1 和 Nav 1.6 的蛋白质水平上调。邻近区域或其他大脑区域（包括前额叶和枕叶皮层）没有发现显着变化。在失神性癫痫的 WAG/Rij 模型中，我们确定了皮质的一个特定区域，即面部体感区域皮质外侧凸面的 II-IV 层神经元，其中钠通道 g-cries Nav 1.1 和 Nav 1.6 的 mRNA 和蛋白表达上调。皮质的这个区域与电生理学确定的癫痫发作区域大致匹配。 Nav1.1 和 Nav1.6 表达的变化与年龄依赖性癫痫发作频率和持续时间的增加平行。 (C) 2003 Elsevier B.V. 保留所有权利。
Due to the involvement of cortical neurons in spike-wave discharge (SWD) initiation, and the contribution of voltage-gated sodium channels (VGSCs) to neuronal firing, we examined alterations in the expression of VGSC mRNA and protein in cortical neurons in the WAG/Rij absence epileptic rat. WAG/Rij rats were compared to age-matched Wistar control rats at 2,4, and 6 months. Continuous EEG data for VGSC mRNA (by quantitative PCR) and protein (by immunocytochemistry). SWDs increased with age in WAG/Rij rats. mRNA levels for sodium channels Nav 1.1 and Nav 1.6, but not Nav 1.2, were found to be up-regulated selectively within the facial somatosensory cortex (at AP + 0.0, ML + 6.0 mm). Protein levels for Nav 1.1 and Nav 1.6 were up-regulated in layer II-IV cortical neurons in this region of cortex. No significant changes were seen in adjacent regions or other brain areas, including the pre-frontal and occipital cortex. In the WAG/Rij model of absence epilepsy, we identified a specific region of cortex, in layer II-IV neurons on the lateral convexity of the cortex in the facial somatosensory area, where mRNA and protein expression of sodium channel g-cries Nav 1.1 and Nav 1.6 are up-regulated. This region of cortex approximately matches the electrophysiologically determined region of seizure onset. Changes in the expression of Nav1.1 and Nav1.6 parallel age-dependent increases in seizure frequency and duration. (C) 2003 Elsevier B.V. All rights reserved.