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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2023

Open Access 01-12-2023 | Hepatic Encephalopathy | Research

Circular RNA Tmcc1 improves astrocytic glutamate metabolism and spatial memory via NF-κB and CREB signaling in a bile duct ligation mouse model: transcriptional and cellular analyses

Authors: Danbi Jo, Yeong-Hwan Lim, Yoon Seok Jung, Young-Kook Kim, Juhyun Song

Published in: Journal of Neuroinflammation | Issue 1/2023

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Abstract

Background

Hepatic encephalopathy-induced hyperammonemia alters astrocytic glutamate metabolism in the brain, which is involved in cognitive decline. To identify specific therapeutic strategies for the treatment of hepatic encephalopathy, various molecular signaling studies, such as non-coding RNA functional study, have been conducted. However, despite several reports of circular RNAs (circRNAs) in the brain, few studies of circRNAs in hepatic encephalopathy-induced neuropathophysiological diseases have been conducted.

Methods

In this study, we performed RNA sequencing to identify whether the candidate circRNA cirTmcc1 is specifically expressed in the brain cortex in a bile duct ligation (BDL) mouse model of hepatic encephalopathy.

Results

Based on transcriptional and cellular analysis, we investigated the circTmcc1-dysregulation-induced changes in the expression of several genes that are associated with intracellular metabolism and astrocyte function. We found that the circTmcc1 binds with the NF-κB p65-CREB transcriptional complex and regulates the expression of the astrocyte transporter EAAT2. Furthermore, circTmcc1 contributed to the secretion of proinflammatory mediators and glutamate metabolism in astrocytes and subsequently modulated an improvement in spatial memory by mediating neuronal synaptic plasticity.

Conclusions

Thus, circTmcc1 may be a promising circRNA candidate for targeted interventions to prevent and treat the neuropathophysiological complications that occur due to hepatic encephalopathy.
Appendix
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Metadata
Title
Circular RNA Tmcc1 improves astrocytic glutamate metabolism and spatial memory via NF-κB and CREB signaling in a bile duct ligation mouse model: transcriptional and cellular analyses
Authors
Danbi Jo
Yeong-Hwan Lim
Yoon Seok Jung
Young-Kook Kim
Juhyun Song
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2023
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-023-02806-w

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