Xu Xin, Yang Xiaoyan, Xiong Yan, Gu Juan, He Changlong, Hu Yida, Xiao Fei, Chen Guojun, Wang Xuefeng
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, China.
J Neurochem. 2015 Apr;133(1):134-43. doi: 10.1111/jnc.13052. Epub 2015 Feb 26.
Mesial temporal lobe epilepsy (MTLE) is characterized by spontaneous recurrent complex partial seizures. Increased neurogenesis and neuronal plasticity have been reported in animal models of MTLE, but not in detail in human MTLE cases. Here, we showed that receptor for activated C kinase 1 (RACK1) was expressed in the hippocampus and temporal cortex of the MTLE human brain. Interestingly, most of the cells expressing RACK1 in the epileptic temporal cortices co-expressed both polysialylated neural cell adhesion molecules, the migrating neuroblast marker, and the beta-tubulin isotype III, an early neuronal marker, suggesting that these cells may be post-mitotic neurons in the early phase of neuronal development. A subpopulation of RACK1-positive cells also co-express neuronal nuclei, a mature neuronal marker, suggesting that epilepsy may promote the generation of new neurons. Moreover, in the epileptic temporal cortices, the co-expression of both axonal and dendritic markers in the majority of RACK1-positive cells hints at enhanced neuronal plasticity. The expression of b-tubulin II (TUBB2B) associated with neuronal migration and positioning, was decreased. This study is the first to successfully identify a single population of cells expressing RACK1 in the human temporal cortex and the brain of the animal model, which can be up-regulated in epilepsy. Therefore, it is possible that these cells are functionally relevant to the pathophysiology of epilepsy.
内侧颞叶癫痫(MTLE)的特征是自发复发性复杂部分性发作。在MTLE动物模型中已报道神经发生增加和神经元可塑性增强,但在人类MTLE病例中尚未详细报道。在此,我们表明活化C激酶1受体(RACK1)在MTLE人脑的海马体和颞叶皮质中表达。有趣的是,癫痫性颞叶皮质中大多数表达RACK1的细胞同时共表达多唾液酸化神经细胞粘附分子、迁移神经母细胞标志物和β-微管蛋白同种型III(一种早期神经元标志物),这表明这些细胞可能是神经元发育早期的有丝分裂后神经元。RACK1阳性细胞的一个亚群也共表达神经元细胞核(一种成熟神经元标志物),这表明癫痫可能促进新神经元的生成。此外,在癫痫性颞叶皮质中,大多数RACK1阳性细胞中轴突和树突标志物的共表达暗示神经元可塑性增强。与神经元迁移和定位相关的β-微管蛋白II(TUBB2B)的表达降低。本研究首次成功鉴定出在人类颞叶皮质和动物模型大脑中表达RACK1的单一细胞群,其在癫痫中可上调。因此,这些细胞可能在功能上与癫痫的病理生理学相关。