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RNA sequencing analysis of cortex and hippocampus in a kainic acid rat model of temporal lobe epilepsy to identify mechanisms and therapeutic targets related to inflammation, immunity and cognition.
International Immunopharmacology ( IF 5.6 ) Pub Date : 2020-07-28 , DOI: 10.1016/j.intimp.2020.106825
Xinyan Dong 1 , Xiaoxu Hao 2 , Peng Xu 3 , Miao Fan 2 , Xuehui Wang 4 , Xin Huang 5 , Peifang Jiang 6 , Linghui Zeng 2 , Yicheng Xie 6
Affiliation  

Temporal lobe epilepsy (TLE) is the most common type of refractory epilepsy, in which inflammation is suggested to cause abnormal neuronal connections and neural networks. However, the expression of inflammatory genes in epilepsy remains incomplete, particularly in the context of the cortex, which is a hub of epileptic transmission but also is essential for mediating sensory, motor and cognitive function. Here, a rat model of epilepsy was established by kainic acid (KA) administration Gene transcriptome was explored in 4 signature phases in the hippocampus and cortex: acute damage (3 h), onset of epileptogenesis (3 d), spontaneous epilepsy (2 w) and cognitive impairment (9 w). Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis was applied to unravel the significantly altered pathways. We found, in both the hippocampus and cortex, the inflammatory gene was up-regulated in the acute phase, followed by a gradual decline; the phagocytosis and glial activation were remarkably increased since day 3; persistently down-regulated synaptic transmission and neuronal development started from the 3 h phase and lasted through the 9 w phase. While, the changed gene expression in the cortex fall into the same categories but were relatively lagging behind that in the hippocampus, also showing less number and distinct genes. Collectively, this study demonstrated the changes of gene transcriptome in the cortex and hippocampus in the signature phases after the KA administration, illustrating the association between epileptogenesis, inflammation genes and cognitive dysfunction, and may benefit identifying novel therapeutic targets for treating TLE and its comorbidities.



中文翻译:

海藻酸大鼠颞叶癫痫模型中皮质和海马的RNA测序分析,以鉴定与炎症,免疫和认知有关的机制和治疗靶标。

颞叶癫痫(TLE)是最常见的难治性癫痫,其中炎症被认为会引起异常的神经元连接和神经网络。然而,炎症基因在癫痫中的表达仍然不完全,特别是在皮质的情况下,皮质是癫痫传播的枢纽,但对于介导感觉,运动和认知功能也是必不可少的。在这里,通过海藻酸(KA)给药建立了癫痫大鼠模型。在海马和皮层的四个特征性阶段探索了基因转录组:急性损伤(3 h),癫痫发生(3 d),自发性癫痫(2 w) )和认知障碍(9 w)。应用了基因本体论(GO)和基因和基因组京都百科全书(KEGG)分析来揭示显着改变的途径。我们找到,在海马和皮层,炎症基因在急性期均上调,然后逐渐下降。从第3天开始,吞噬作用和神经胶质激活显着增加。持续下调的突触传递和神经元发育从3 h阶段开始,一直持续到9 w阶段。同时,皮层中改变的基因表达属于同一类别,但相对落后于海马,也显示出更少的数量和独特的基因。总的来说,这项研究证明了KA给药后,特征性阶段皮质和海马基因转录组的变化,说明了癫痫发生,炎症基因与认知功能障碍之间的关系,

更新日期:2020-07-28
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