Comprehensive Analysis of lncRNAs, miRNAs and mRNAs in Mouse Hippocampus With Hepatic Encephalopathy

Abstract

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.

Zhi‐zi‐chi decoction mitigates depression by enhancing lncRNA Six3os1 expression and promoting histone H3K4 methylation at the BDNF promoter

“…Geniposide, an iridoid glycoside derived from Fructus Gardeniae , has been reported to upregulate the expression of long non‐coding RNA (lncRNA) Six3os1 in CUMS‐induced neurons 17 . In NH4Cl‐treated hippocampal neurons, the dendritic spine density and maturity are decreased, while silencing of Six3os1 can reverse this decrease 18 . Additionally, Six3os1 upregulation is capable of ameliorating the oxidative stress of neurons in CUMS‐induced mice with depression‐like behaviours 17 …”

“…17 In NH4Cl-treated hippocampal neurons, the dendritic spine density and maturity are decreased, while silencing of Six3os1 can reverse this decrease. 18 Additionally, Six3os1 upregulation is capable of ameliorating the oxidative stress of neurons in CUMS-induced mice with depression-like behaviours. 17 Six3os1 can bind to lysine (K) methyltransferase 2a (KMT2A), as predicted by the catRAPID website.…”

Experimental hepatic encephalopathy causes early but sustained glial transcriptional changes

“…To illustrate, transcriptome evaluation of brain samples of both HE patients and hyperammonemic models shows relatively little changes compared to control conditions. Moreover, these changes are not consistent between different model systems or even different brain regions within one model system [ 17 – 19 ]. Given the cellular heterogeneity and complexity of the central nervous system (CNS), changes in specific cell types might be masked when assessing crude tissue.…”