Abstract
Background Hyperammonemia can result in various neuropathologies, including sleep disturbance, memory loss, and motor dysfunction in hepatic encephalopathy. Long noncoding RNA (lncRNA) as a group of noncoding RNA longer than 200 nucleotides is emerging as a promising therapeutic target to treat diverse diseases. Although lncRNAs have been linked to the pathogenesis of various diseases, their function in hepatic encephalopathy has not yet been elucidated. Research Design and Methods. To identify the roles of lncRNAs in hepatic encephalopathy brain, we used a bile duct ligation (BDL) mouse model and examined the alteration of neuronal cell death markers and neuronal structure-related proteins in BDL mouse cortex tissue. Furthermore, analysis of the transcriptome of BDL mouse brain cortex tissues revealed several lncRNAs critical to the apoptosis and neuronal structural changes associated with hepatic encephalopathy. Results We confirmed the roles of the lncRNAs, ZFAS1, and GAS5 as strong candidate lncRNAs to regulate neuropathologies in hepatic encephalopathy. Our data revealed the roles of lncRNAs, ZFAS1, and GAS5, on neuronal cell death and neural structure in hyperammonemia in in vivo and in vitro conditions. Conclusion Thus, we suggest that the modulation of these lncRNAs may be beneficial for the treatment of hepatic encephalopathy.
Highlights
Hepatic encephalopathy is considered as a consequence of liver failure, including in cases of severe liver cirrhosis [1]
To confirm whether bile duct ligation (BDL) affects the expression of a neuronal marker protein in cerebral cortex tissue, we first evaluated the expression of NeuN, a neuronal marker to assess a pathological condition of neurons
Hepatic encephalopathy is characterized by aberrant increases in ammonia levels in the blood and brain, which leads to neurological impairment [32] and neuronal cell death [9]
Summary
Hepatic encephalopathy is considered as a consequence of liver failure, including in cases of severe liver cirrhosis [1]. Ammonia levels in the blood and cerebrospinal fluids were elevated in the patients with hepatic encephalopathy [6]. Hyperammonemia can result in various neuropathologies, including sleep disturbance, memory loss, and motor dysfunction in hepatic encephalopathy. To identify the roles of lncRNAs in hepatic encephalopathy brain, we used a bile duct ligation (BDL) mouse model and examined the alteration of neuronal cell death markers and neuronal structure-related proteins in BDL mouse cortex tissue. Analysis of the transcriptome of BDL mouse brain cortex tissues revealed several lncRNAs critical to the apoptosis and neuronal structural changes associated with hepatic encephalopathy. Our data revealed the roles of lncRNAs, ZFAS1, and GAS5, on neuronal cell death and neural structure in hyperammonemia in in vivo and in vitro conditions. We suggest that the modulation of these lncRNAs may be beneficial for the treatment of hepatic encephalopathy
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