Zhang Huijie, Zhang Wenjun, Yu Guangyin, Li Fang, Hui Yuqing, Cha Shuhan, Chen Meiying, Zhu Wei, Zhang Jifeng, Guo Guoqing, Gong Xiaobing
Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, China.
Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Front Genet. 2022 May 5;13:868716. doi: 10.3389/fgene.2022.868716. eCollection 2022.
Hepatic encephalopathy (HE) often presents with varying degrees of cognitive impairment. However, the molecular mechanism of its cognitive impairment has not been fully elucidated. Whole transcriptome analysis of hippocampus between normal and HE mice was performed by using RNA sequencing. 229 lncRNAs, 49 miRNAs and 363 mRNAs were differentially expressed in HE mice. The lncRNA-miRNA-mRNA interaction networks were established, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Dysregulated RNAs in interaction networks were mainly involved in synaptic plasticity and the regulation of learning and memory. In NH4Cl-treated hippocampal neurons, the dendritic spine density and maturity decreased significantly, the amplitude and frequency of mIPSC increased, while the amplitude and frequency of mEPSC decreased. These manifestations can be reversed by silencing SIX3OS1. Further research on these no-coding RNAs may lead to new therapies for the treatment and management of brain dysfunction caused by HE.
肝性脑病（HE）常伴有不同程度的认知障碍。然而，其认知障碍的分子机制尚未完全阐明。通过RNA测序对正常小鼠和HE小鼠的海马进行全转录组分析。在HE小鼠中，有229个长链非编码RNA（lncRNA）、49个微小RNA（miRNA）和363个信使RNA（mRNA）差异表达。构建了lncRNA-miRNA-mRNA相互作用网络，并进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析。相互作用网络中失调的RNA主要参与突触可塑性以及学习和记忆的调节。在氯化铵处理的海马神经元中，树突棘密度和成熟度显著降低，微小抑制性突触后电流（mIPSC）的幅度和频率增加，而微小兴奋性突触后电流（mEPSC）的幅度和频率降低。沉默SIX3OS1可逆转这些表现。对这些非编码RNA的进一步研究可能会为治疗和管理由HE引起的脑功能障碍带来新的疗法。
