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Dynamic Change of Shanks Gene mRNA Expression and DNA Methylation in Epileptic Rat Model and Human Patients.
Molecular Neurobiology ( IF 4.6 ) Pub Date : 2020-06-21 , DOI: 10.1007/s12035-020-01968-5
Yujiao Fu 1, 2 , Du Liu 1, 2, 3 , Jialing Guo 1, 2 , Hongyu Long 1, 2 , Wenbiao Xiao 1, 2 , Wei Xiao 1, 2 , Li Feng 1, 2 , Zhaohui Luo 1, 2 , Bo Xiao 1, 2
Affiliation  

Synaptic protein shanks (SH3 and multiple ankyrin repeat domains protein, Shank) have emerged as an important mediator of synaptic remodeling. Synaptic remodeling is a common pathogenic process in various neurological disorders including epilepsy. However, the expression and function of shanks gene in epileptogenesis has not been investigated to date. Herein, we investigated the expression of shanks (shank1/2/3) mRNA expression in both epileptic rats and epilepsy patients. Furthermore, methyl target sequencing was applied to explore the relationship between shank mRNA expression and DNA methylation in both rats and human patients. In general rat model, shank1/2/3 mRNA was downregulated at acute stage, upregulated at latent stage, and returned to the basal level at chronic stage. Ten CpG sites of shank1 was found differentially methylated, out of which 6 were hypermethylated. Seventeen CpG sites of shank3 were differentially methylated, out of which 8 were hypermethylated. In human epilepsy patients, decreased shank2 mRNA was detected from the brain tissue, with DNA hypermethylation dominant from both brain (18 out of 30) and blood tissue (58 out of 80), indicating the regulation role of DNA methylation on shank2 expression. In conclusion, our finding suggests the participation of the shanks gene in the pathophysiology of seizure, out of which 2 shank3 CpG sites (Chr7: 130473419, and Chr7: 130473405) may play an important role in shank3 expression at both the acute and latent stages in the SE rat model.



中文翻译:

癫痫大鼠模型和人类患者Shanks基因mRNA表达和DNA甲基化的动态变化。

突触蛋白小腿(SH3和多个锚蛋白重复域蛋白Shank)已成为突触重塑的重要介体。突触重塑是包括癫痫在内的各种神经系统疾病的常见致病过程。然而,迄今为止尚未研究小腿基因在癫痫发生中的表达和功能。在本文中,我们调查了癫痫大鼠和癫痫患者小腿(shank1 / 2/3)mRNA的表达。此外,使用甲基靶标测序来研究大鼠和人类患者小腿mRNA表达与DNA甲基化之间的关系。在普通大鼠模型中,shank1 / 2/3 mRNA在急性期下调,在潜伏期上调,并在慢性期恢复到基础水平。发现shank1的10个CpG位点差异甲基化,其中6个是高甲基化的。shank3的17个CpG位点被差异甲基化,其中8个被高度甲基化。在人类癫痫患者中,从脑组织中检测到shank2 mRNA的下降,而大脑(30个中的18个)和血液组织(80个中的58个)均以DNA高甲基化为主,表明DNA甲基化对shank2表达的调节作用。总之,我们的发现表明,shanks基因参与了癫痫发作的病理生理,其中两个shank3 CpG位点(Chr7:130473419和Chr7:130473405)可能在急性和潜伏期均在shank3表达中起重要作用。在SE大鼠模型中。从脑组织中检测到shank2 mRNA的水平降低,而大脑(30个中的18个)和血液组织(80个中的58个)的DNA高甲基化占主导,表明DNA甲基化对shank2表达的调节作用。总之,我们的发现表明,shanks基因参与了癫痫发作的病理生理,其中两个shank3 CpG位点(Chr7:130473419和Chr7:130473405)可能在急性和潜伏期均在shank3表达中起重要作用。在SE大鼠模型中。从脑组织中检测到shank2 mRNA的水平降低,而大脑(30个中的18个)和血液组织(80个中的58个)的DNA高甲基化占主导,表明DNA甲基化对shank2表达的调节作用。总之,我们的发现表明,shanks基因参与了癫痫发作的病理生理,其中两个shank3 CpG位点(Chr7:130473419和Chr7:130473405)可能在急性和潜伏期均在shank3表达中起重要作用。在SE大鼠模型中。

更新日期:2020-06-22
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