High urea induces anxiety disorders associated with chronic kidney disease by promoting abnormal proliferation of OPC in amygdala

• Published in: European journal of pharmacology 2023-10, Vol.957, p.175905-175905, Article 175905
• Main Authors: Huang, Boyue, Huang, Zhizhen, Wang, Hongkai, Zhu, Guoqi, Liao, Hui, Wang, Zhiwen, Yang, Baoxue, Ran, Jianhua
• Format: Article
• Language: English
• Subjects: Amygdala; Anxiety; Chronic kidney disease; Oligodendrocytes; Urea
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2023.175905

Chronic kidney disease (CKD) with anxiety disorder is of a great concern due to its high morbidity and mortality. Urea, as an important toxin in CKD, is not only a pathological factor for complications in patients with CKD, but also is accumulated in the brain of aging and neurodegenerative diseases. However, the pathological role and underlying regulatory mechanism of urea in CKD related mood disorders have not been well established. We previously reported a depression phenotype in mice with abnormal urea metabolism. Since patients with depression are more likely to suffer from anxiety, we speculate that high urea may be an important factor causing anxiety in CKD patients. In adenine-induced CKD mouse model and UT-B−/− mouse model, multiple behavioral studies confirmed that high urea induces anxiety-like behavior. Single-cell transcriptome revealed that down-regulation of Egr1 induced compensatory proliferation of oligodendrocyte progenitor cells (OPC). Myelin-related signaling pathways of oligodendrocytes (OL) were change significant in the urea accumulation amygdala. The study showed that high urea downregulated Egr1 with subsequent upregulation of ERK pathways in OPCs. These data indicate that the pathological role and molecular mechanism of high urea in CKD-related anxiety, and provide objective serological indicator and a potential new drug target for the prevention and treatment of anxiety in CKD patients. [Display omitted] •Urea is a serological indicator of Chronic kidney disease comorbid anxiety disorder.•Oligodendrocyte cell lines, mainly in the amygdala, proliferate abnormally in high urea mice.•The abnormal Oligodendrocyte precursor cells proliferation was mediated by the Egr1-ERK signaling pathway.