Altered Protein Profiles During Epileptogenesis in the Pilocarpine Mouse Model of Temporal Lobe Epilepsy.
Altered Protein Profiles During Epileptogenesis in the Pilocarpine Mouse Model of Temporal Lobe Epilepsy.
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DOI：
10.3389/fneur.2021.654606
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发表时间：
2021
影响因子：
3.4
通讯作者：
Brooks-Kayal A
中科院分区：
文献类型：
--
作者：
Ahmed MM;Carrel AJ;Cruz Del Angel Y;Carlsen J;Thomas AX;González MI;Gardiner KJ;Brooks-Kayal A
癫痫的特点是反复发作，自发性癫痫发作，是全球神经系统疾病负担的主要贡献者。虽然癫痫可以由各种脑损伤引起，但在许多情况下，原因是未知的，并且在很大一部分情况下，癫痫发作无法通过现有的治疗来控制。了解癫痫发生的基础或触发的分子改变将有助于确定预防或控制癫痫进展的治疗方法。为此，中等通量技术的反相蛋白质阵列（RPPA）被用来分析获得性癫痫的毛果芸香碱小鼠模型中蛋白质表达的变化。在诱导癫痫持续状态后15分钟至2周的6个时间点，测量了小鼠海马、皮质和小脑中54种蛋白质的水平，这些蛋白质包括主要信号通路和细胞复合物的磷酸化依赖性和磷酸化非依赖性组分。结果说明了通常研究的MTOR途径组分pS 6水平的时间依赖性，并首次显示了MTOR、MAPK、JAK/STAT和凋亡途径、NMDA受体和其他细胞复合物的多个组分在癫痫发生期间的详细反应。还注意到影响神经元和神经胶质的功能相关蛋白质水平之间的相关性的时间和脑区域特异性变化。虽然海马和皮质是匹罗卡品诱导癫痫的主要研究区域，但小脑也显示出显著的时间依赖性分子反应。
Epilepsy is characterized by recurrent, spontaneous seizures and is a major contributor to the global burden of neurological disease. Although epilepsy can result from a variety of brain insults, in many cases the cause is unknown and, in a significant proportion of cases, seizures cannot be controlled by available treatments. Understanding the molecular alterations that underlie or are triggered by epileptogenesis would help to identify therapeutics to prevent or control progression to epilepsy. To this end, the moderate throughput technique of Reverse Phase Protein Arrays (RPPA) was used to profile changes in protein expression in a pilocarpine mouse model of acquired epilepsy. Levels of 54 proteins, comprising phosphorylation-dependent and phosphorylation-independent components of major signaling pathways and cellular complexes, were measured in hippocampus, cortex and cerebellum of mice at six time points, spanning 15 min to 2 weeks after induction of status epilepticus. Results illustrate the time dependence of levels of the commonly studied MTOR pathway component, pS6, and show, for the first time, detailed responses during epileptogenesis of multiple components of the MTOR, MAPK, JAK/STAT and apoptosis pathways, NMDA receptors, and additional cellular complexes. Also noted are time- and brain region- specific changes in correlations among levels of functionally related proteins affecting both neurons and glia. While hippocampus and cortex are primary areas studied in pilocarpine-induced epilepsy, cerebellum also shows significant time-dependent molecular responses.
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影响因子：
5.3
作者：
Li, Yi;Peng, Zechun;Xiao, Bo;Houser, Carolyn R.
通讯作者：
Houser, Carolyn R.
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56.9
作者：
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通讯作者：
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3.5
作者：
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