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

作者全名："Huang, Boyue; Huang, Zhizhen; Wang, Hongkai; Zhu, Guoqi; Liao, Hui; Wang, Zhiwen; Yang, Baoxue; Ran, Jianhua"

作者地址："[Huang, Boyue; Zhu, Guoqi; Liao, Hui; Wang, Zhiwen; Ran, Jianhua] Chongqing Med Univ, Basic Med Coll, Dept Anat, Chongqing, Peoples R China; [Huang, Boyue; Zhu, Guoqi; Liao, Hui; Wang, Zhiwen; Ran, Jianhua] Chongqing Med Univ, Basic Med Coll, Lab Neurosci & Tissue Engn, Chongqing, Peoples R China; [Huang, Boyue; Huang, Zhizhen; Yang, Baoxue] Peking Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing, Peoples R China; [Huang, Boyue; Huang, Zhizhen; Yang, Baoxue] Peking Univ, State Key Lab Vasc Homeostasis & Remodeling, Beijing, Peoples R China; [Wang, Hongkai] Northwestern Univ, Dept Phys Med & Rehabil, Lab Regenerat Rehabil, Shirley Ryan Abil Lab,Feinberg Sch Med 2,Interdept, Evanston, IL USA; [Ran, Jianhua] Chongqing Med Univ, Key Lab Major Brain Dis & Aging Res, Minist Educ, Chongqing, Peoples R China; [Ran, Jianhua] Chongqing Med Univ, Inst Brain Sci & Dis, Chongqing, Peoples R China"

通信作者："Ran, JH (通讯作者)，Chongqing Med Univ, Basic Med Coll, Dept Anat, Chongqing, Peoples R China.; Ran, JH (通讯作者)，Chongqing Med Univ, Basic Med Coll, Lab Neurosci & Tissue Engn, Chongqing, Peoples R China.; Yang, BX (通讯作者)，Peking Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing, Peoples R China.; Yang, BX (通讯作者)，Peking Univ, State Key Lab Vasc Homeostasis & Remodeling, Beijing, Peoples R China."

来源：EUROPEAN JOURNAL OF PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001077221300001

JCR分区：Q1

影响因子：5

年份：2023

卷号：957

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Urea; Chronic kidney disease; Anxiety; Oligodendrocytes; Amygdala

摘要："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 downregulation of Egr1 induced compensatory proliferation of oligodendrocyte progenitor cells (OPC). Myelinrelated 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."

基金机构："National Natural Science Foundation of China [82273999, 81620108029, 81330074, 81770738, 82370739, 81974083]; Chongqing Postdoctoral Science Foundation of Chongqing Science and Technology Commission [CSTB2022NSCQ-BHX0714]; Postdoctoral Fellowship Program of Chongqing Medical University; Beijing Natural Science Foundation [7212151]; Central Research Institute Fund of Chinese Academy of Medical Sciences [2022-JKCS-15]"

基金资助正文："This work was supported by grants from the National Natural Science Foundation of China grants 82273999, 81620108029, 81330074, 81770738, 82370739 and 81974083; Chongqing Postdoctoral Science Foundation of Chongqing Science and Technology Commission (CSTB2022NSCQ-BHX0714); the Postdoctoral Fellowship Program of Chongqing Medical University; the Beijing Natural Science Foundation grant 7212151; and a grant from the non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2022-JKCS-15)."