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Genetic deletion of microRNA-22 blunts the inflammatory transcriptional response to status epilepticus and exacerbates epilepsy in mice.
Molecular Brain ( IF 3.3 ) Pub Date : 2020-08-21 , DOI: 10.1186/s13041-020-00653-x
Luiz F Almeida Silva 1 , Cristina R Reschke 1, 2 , Ngoc T Nguyen 1, 2 , Elena Langa 1, 2 , Amaya Sanz-Rodriguez 1, 2 , Rogerio R Gerbatin 1, 2 , Fernanda R Temp 1, 3 , Mayara L de Freitas 1, 3 , Ronan M Conroy 4 , Gary P Brennan 1, 2, 5 , Tobias Engel 1, 2 , David C Henshall 1, 2
Affiliation  

MicroRNAs perform important roles in the post-transcriptional regulation of gene expression. Sequencing as well as functional studies using antisense oligonucleotides indicate important roles for microRNAs during the development of epilepsy through targeting transcripts involved in neuronal structure, gliosis and inflammation. MicroRNA-22 (miR-22) has been reported to protect against the development of epileptogenic brain networks through suppression of neuroinflammatory signalling. Here, we used mice with a genetic deletion of miR-22 to extend these insights. Mice lacking miR-22 displayed normal behaviour and brain structure and developed similar status epilepticus after intraamygdala kainic acid compared to wildtype animals. Continuous EEG monitoring after status epilepticus revealed, however, an accelerated and exacerbated epilepsy phenotype whereby spontaneous seizures began sooner, occurred more frequently and were of longer duration in miR-22-deficient mice. RNA sequencing analysis of the hippocampus during the period of epileptogenesis revealed a specific suppression of inflammatory signalling in the hippocampus of miR-22-deficient mice. Taken together, these findings indicate a role for miR-22 in establishing early inflammatory responses to status epilepticus. Inflammatory signalling may serve anti-epileptogenic functions and cautions the timing of anti-inflammatory interventions for the treatment of status epilepticus.

中文翻译:

microRNA-22的基因删除钝化了对癫痫持续状态的炎性转录反应,并加剧了小鼠的癫痫病。

MicroRNA在基因表达的转录后调控中发挥重要作用。使用反义寡核苷酸进行的测序和功能研究表明,microRNA在癫痫发展过程中的重要作用是通过靶向涉及神经元结构,神经胶质化和炎症的转录本。据报道,MicroRNA-22(miR-22)通过抑制神经炎性信号传导来防止癫痫性脑网络的发展。在这里,我们使用具有miR-22基因缺失的小鼠来扩展这些见解。与野生型动物相比,缺乏miR-22的小鼠在杏仁淀粉内海藻酸后表现出正常的行为和大脑结构,并发展出相似的癫痫状态。然而,持续癫痫持续状态监测显示 在miR-22缺陷型小鼠中,癫痫表型加速并加剧,自发性癫痫发作开始得更快,发作频率更高,持续时间更长。癫痫发生期间海马的RNA测序分析揭示了miR-22缺陷小鼠海马中炎症信号的特异性抑制。综上所述,这些发现表明miR-22在建立对癫痫持续状态的早期炎症反应中的作用。炎性信号传导可能起到抗癫痫的作用,并提醒您采取消炎干预措施治疗癫痫持续状态。癫痫发生期间海马的RNA测序分析揭示了miR-22缺陷小鼠海马中炎症信号的特异性抑制。综上所述,这些发现表明miR-22在建立对癫痫持续状态的早期炎症反应中的作用。炎性信号传导可能起到抗癫痫的作用,并提醒您采取消炎性干预措施治疗癫痫持续状态。癫痫发生期间海马的RNA测序分析揭示了miR-22缺陷小鼠海马中炎症信号的特异性抑制。综上所述,这些发现表明miR-22在建立对癫痫持续状态的早期炎症反应中的作用。炎性信号传导可能起到抗癫痫的作用,并提醒您采取消炎干预措施治疗癫痫持续状态。
更新日期:2020-08-21
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