Predicted molecules and signaling pathways for regulating seizures in the hippocampus in lithium-pilocarpine induced acute epileptic rats: A proteomics study.
Predicted molecules and signaling pathways for regulating seizures in the hippocampus in lithium-pilocarpine induced acute epileptic rats: A proteomics study.
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DOI：
10.3389/fncel.2022.947732
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发表时间：
2022
影响因子：
5.3
通讯作者：
Ma, Huisheng
中科院分区：
文献类型：
--
作者：
Wang, Peng;Yang, Lu;Yang, Rang;Chen, Zhangping;Ren, Xiaofan;Wang, Fangjiao;Jiao, Yan;Ding, Yuxin;Yang, Fengyuan;Sun, Tao;Ma, Huisheng
锂-匹罗卡品诱导的啮齿动物模型中的癫痫发作以高度同构的方式模拟人类癫痫发作。海马体是一个产生和传播癫痫发作的大脑区域。为了了解海马中发生的癫痫发作事件的早期阶段，使用基于串联质量标签的蛋白质组学方法分析了锂-匹罗卡品诱导的急性癫痫大鼠模型中第1天和第3天海马中的总体蛋白质表达水平。我们的研究结果表明，差异表达的蛋白质可能是增强，而不是禁止在调制癫痫发作活动的第1和第3天在锂-毛果芸香碱诱导的癫痫大鼠。差异调节的蛋白质在癫痫大鼠中在第1天和第3天不同，表明锂-匹罗卡品给药后第1天至第3天发生的癫痫发作事件涉及不同的分子和途径。在亚细胞分布方面，结果表明，癫痫发作后的海马细胞功能可能是调节癫痫发作进展的差异方式。基因本体注释结果表明，在锂-匹罗卡品给药后第1天，可能需要调节大分子复合物组装和细胞死亡，而在第3天，可能需要调节蛋白质代谢过程、细胞质和蛋白质结合。锂-匹罗卡品给药后第3天，蛋白质代谢过程而不是大分子复合物组装和细胞死亡受到影响。细胞外基质，受体和质膜的构成改变最强烈的癫痫发作事件的发展。在KEGG途径富集聚类分析中，所鉴定的信号传导途径与持续的血管生成和逃避凋亡以及补体和凝血级联相关。在第3天，与亨廷顿病相关的通路和肿瘤坏死因子信号传导最普遍。这些结果表明，癫痫发作事件发生在第1天调节大分子复合物组装和细胞死亡，并在第3天调节生物蛋白质代谢过程。总之，我们的研究发现，在锂-匹罗卡品诱导的动物模型海马中持续癫痫发作事件的证据有限;然而，评估蛋白质的整体差异表达及其对生物功能的影响可能为未来研究癫痫发生提供新的视角。
Seizures in rodent models that are induced by lithium-pilocarpine mimic human seizures in a highly isomorphic manner. The hippocampus is a brain region that generates and spreads seizures. In order to understand the early phases of seizure events occurring in the hippocampus, global protein expression levels in the hippocampus on day 1 and day 3 were analyzed in lithium-pilocarpine induced acute epileptic rat models using a tandem mass tag-based proteomic approach. Our results showed that differentially expressed proteins were likely to be enhanced rather than prohibited in modulating seizure activity on days 1 and 3 in lithium-pilocarpine induced seizure rats. The differentially regulated proteins differed on days 1 and 3 in the seizure rats, indicating that different molecules and pathways are involved in seizure events occurring from day 1 to day 3 following lithium-pilocarpine administration. In regard to subcellular distribution, the results suggest that post-seizure cellular function in the hippocampus is possibly regulated in a differential manner on seizure progression. Gene ontology annotation results showed that, on day 1 following lithium-pilocarpine administration, it is likely necessary to regulate macromolecular complex assembly, and cell death, while on day 3, it may be necessary to modulate protein metabolic process, cytoplasm, and protein binding. Protein metabolic process rather than macromolecular complex assembly and cell death were affected on day 3 following lithium-pilocarpine administration. The extracellular matrix, receptors, and the constitution of plasma membranes were altered most strongly in the development of seizure events. In a KEGG pathway enrichment cluster analysis, the signaling pathways identified were relevant to sustained angiogenesis and evading apoptosis, and complement and coagulation cascades. On day 3, pathways relevant to Huntington’s disease, and tumor necrosis factor signaling were most prevalent. These results suggest that seizure events occurring in day 1 modulate macromolecular complex assembly and cell death, and in day 3 modulate biological protein metabolic process. In summary, our study found limited evidence for ongoing seizure events in the hippocampus of lithium-pilocarpine induced animal models; nevertheless, evaluating the global differential expression of proteins and their impacts on bio-function may offer new perspectives for studying epileptogenesis in the future.
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影响因子：
3.8
作者：
Begcevic I;Kosanam H;Martínez-Morillo E;Dimitromanolakis A;Diamandis P;Kuzmanov U;Hazrati LN;Diamandis EP
通讯作者：
Diamandis EP
影响因子：
25
作者：
Kim, Seho;Burette, Alain;Kim, Eunjoon
通讯作者：
Kim, Eunjoon
DOI：
10.1073/pnas.0611609104
发表时间：
2007-03-06
影响因子：
11.1
作者：
Huang, Yunfei;Higginson, Daniel S.;Snyder, Solomon H.
通讯作者：
Snyder, Solomon H.
影响因子：
5.6
作者：
CAVALHEIRO, EA;LEITE, JP;TURSKI, L
通讯作者：
TURSKI, L
影响因子：
3.3
作者：
CLIFFORD, DB;OLNEY, JW;ZORUMSKI, CF
通讯作者：
ZORUMSKI, CF