Expression of astrocyte-related receptors in cortical dysplasia with intractable epilepsy.
Expression of astrocyte-related receptors in cortical dysplasia with intractable epilepsy.
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DOI：
10.1097/nen.0000000000000099
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发表时间：
2014-08
影响因子：
3.2
通讯作者：
S. Sukigara;H. Dai;S. Nabatame;T. Otsuki;Sae Hanai;R. Honda;Takashi Saito;E. Nakagawa;T. Kaido;N. Sato;Y. Kaneko;A. Takahashi;K. Sugai;Yuko Saito;M. Sasaki;Y. Goto;S. Koizumi;M. Itoh
中科院分区：
文献类型：
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作者：
S. Sukigara;H. Dai;S. Nabatame;T. Otsuki;Sae Hanai;R. Honda;Takashi Saito;E. Nakagawa;T. Kaido;N. Sato;Y. Kaneko;A. Takahashi;K. Sugai;Yuko Saito;M. Sasaki;Y. Goto;S. Koizumi;M. Itoh
癫痫是一种重要的神经系统疾病，星形胶质细胞在癫痫发生中起着重要作用。为了研究星形细胞相关受体在顽固性癫痫伴局灶性皮质发育不良（FCD）及其他疾病患者中的可能作用，我们检查了31例切除的癫痫灶，包括23例FCD I型、IIa型或IIb型，5例结节性硬化症，3例低度星形细胞瘤。对照样本来自21例无癫痫或神经功能缺损的尸检脑和5例无癫痫的病理性神经胶质瘤患者。对嘌呤能受体P2RY1、P2RY2、P2RY4亚型、钾通道Kv4.2和Kir4.1以及代谢受体mGluR1和mGluR5亚型的抗体进行免疫组化和免疫印迹分析。用抗胶质纤维酸性蛋白、抗neun和抗cd68免疫染色分别鉴定星形胶质细胞、神经元和小胶质细胞。癫痫患者脑样本中大多数胶质纤维酸性蛋白免疫阳性星形胶质细胞为P2RY1-、P2RY2-、P2RY4-、Kv4.2-、Kir4.1-、mGluR1-和mglur5阳性，而对照和病理性胶质细胞病样本中这些星形胶质细胞相关受体的表达水平较低。我们的研究结果表明，尽管这些受体是星形胶质细胞传递、神经元-胶质网络形成和其他生理功能所必需的，但顽固性癫痫患者大脑中的过度表达可能与细胞内和胶质神经元信号通路的激活有关，这些信号通路有助于癫痫的发生。
Epilepsy is one of the major neurologic diseases, and astrocytes play important roles in epileptogenesis. To investigate possible roles of astrocyte-related receptors in patients with intractable epilepsy associated with focal cortical dysplasia (FCD) and other conditions, we examined resected epileptic foci from 31 patients, including 23 with FCD type I, IIa, or IIb, 5 with tuberous sclerosis complex, and 3 with low-grade astrocytoma. Control samples were from 21 autopsied brains of patients without epilepsy or neurologic deficits and 5 patients with pathologic gliosis without epilepsy. Immunohistochemical and immunoblot analyses with antibodies against purinergic receptor subtypes P2RY1, P2RY2, P2RY4, potassium channels Kv4.2 and Kir4.1, and metabotropic receptor subtypes mGluR1 and mGluR5 were performed. Anti-glial fibrillary acidic protein, anti-NeuN, and anti-CD68 immunostaining was used to identify astrocytes, neurons, and microglia, respectively. Most glial fibrillary acidic protein-immunopositive astrocyte cells in the brain samples from patients with epilepsy were P2RY1-, P2RY2-, P2RY4-, Kv4.2-, Kir4.1-, mGluR1-, and mGluR5-positive, whereas samples from controls and pathologic gliosis showed lower expression levels of these astrocyte-related receptors. Our findings suggest that, although these receptors are necessary for astrocyte transmission, formation of the neuron-glia network, and other physiologic functions, overexpression in the brains of patients with intractable epilepsy may be associated with activation of intracellular and glio-neuronal signaling pathways that contribute to epileptogenesis.