Ammonium induced dysfunction of 5-HT2B receptor in astrocytes.
Authors of this article are:
Yue T, Li B, Gu L, Huang J, Verkhratsky A, Peng L.
A summary of the article is shown below:
Previously we reported that gene expression of astrocytic 5-HT2B receptors was decreased in brains of depressed animals exposed to chronic mild stress (CMS) (Li et al., 2012) and of Parkinson’s disease (Zhang et al., 2015; Song et al., 2018). Depression is also one of the psychiatric symptoms in hyperammonemia, and astrocyte is a primary target of ammonium in brain in vivo. In the present study, we have used preparations of the brains of urease-treated mice and ammonium-treated astrocytes in culture to study gene expression and function of 5-HT2B receptors. The urease-treated mice showed depressive behaviour. Both mRNA and protein of 5-HT2B receptors were increased in the brains of urease-treated mice and in ammonium-treated cultured astrocytes. Further study revealed that mRNA and protein expression of adenosine deaminase acting on RNA 2 (ADAR2), an enzyme catalyze RNA deamination of adenosine to inosine was increased in the brains of urease-treated mice and in ammonium-treated cultured astrocytes. This increase in ADAR2 induced RNA editing of 5-HT2B receptors. Cultured astrocytes treated with ammonium lost 5-HT induced Ca2+ signalling and ERK1/2 phosphorylation, indicating dysfunction of 5-HT2B receptors. This is in agreement with our previous observation that edited 5-HT2B receptors no longer respond to 5-HT (Hertz et al., 2014). Ammonium effects are inhibited by ADAR2 siRNA in cultured astrocytes, suggesting that increased gene expression and editing and loss of function of 5-HT2B receptors are results of increased activity of ADAR2. In summary, we have demonstrated that functional malfunction of astrocytic 5-HT2B receptors occurs in animal models of major depression, Parkinson depression and hepatic encephalopathy albeit via different mechanisms. Understanding the role of astrocytic 5-HT2B receptors in different pathological contexts may instigate development of novel therapeutic strategies for treating disease-specific depressive behaviour.Copyright © 2019. Published by Elsevier Ltd.
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This article is a good source of information and a good way to become familiar with topics such as: 5-HT(2B) receptor; ADAR2; Ammonium; Astrocytes; Depression; Hyperammonemia.