ALG13 Deficiency Associated with Increased Seizure Susceptibility and Severity
ALG13 Deficiency Associated with Increased Seizure Susceptibility and Severity
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ALG13 缺乏与癫痫发作易感性和严重程度增加相关
DOI：
10.1016/j.neuroscience.2019.03.009
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发表时间：
2019-06-15
期刊：
影响因子：
3.3
通讯作者：
Sun, Tao
中科院分区：
文献类型：
--
作者：
Gao, Peng;Wang, Feng;Sun, Tao
ALG 13（天冬酰胺连接糖基化13同源物）编码参与N-连接糖基化过程的关键蛋白，并且异常N-连接糖基化被认为是导致神经缺陷和障碍的重要风险因素。然而，ALG 13和癫痫之间的因果关系仍然未知。本研究应用红藻氨酸（KA）诱导的癫痫小鼠模型，以确定ALG 13缺乏是否导致癫痫发作的易感性和严重性增加。本研究发现，ALG 13在中枢神经系统（CNS）的表达具有组织学和细胞学特异性，主要表达于皮层和海马的神经元中，是癫痫的常见发病部位。此外，KA诱导的癫痫发作显著影响野生型（WT）小鼠前脑中ALG 13 mRNA和蛋白的表达水平。KA诱导的癫痫进展在Alg 13基因敲除（KO）小鼠中显著增加，包括延长的电图癫痫发作、显著增加的死亡率和对癫痫发作的反应的严重性。此外，KA诱导的癫痫相关的脑病理变化主要在Alg 13 KO小鼠中加重。本研究还通过显示Alg 13 KO小鼠皮层和海马中过度活跃的mTOR信号通路，初步探讨了ALG 13参与癫痫的可能机制。据我们所知，这份报告是ALG 13与实验动物癫痫之间关联的第一个证据。(C)2019年IBRO。由爱思唯尔有限公司出版。保留所有权利。
ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders. However, the causal relationship between ALG13 and epilepsy remains unknown. This study applied a kainic acid (KA)-induced epileptic mouse model to determine whether ALG13 deficiency resulted in increased susceptibility to and severity of epileptic seizures. This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs. In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice. KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures. Furthermore, KA-induced epilepsy-related pathological changes of the brain were predominantly exacerbated in Alg13 KO mice. This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice. To the best of our knowledge, this report is the first evidence of the association between ALG13 and epilepsy in experimental animals. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.