RAGE signaling pathway is involved in CUS-induced depression-like behaviors by regulating the expression of NR2A and NR2B in rat hippocampus DG

作者全名："Zhang, Longjie; Luo, Lan; Xue, Lifen; Ran, Dongzhi; Yang, Fang; Tang, Qiang; Jiang, Wengao"

作者地址："[Zhang, Longjie; Luo, Lan; Xue, Lifen; Ran, Dongzhi; Yang, Fang; Tang, Qiang; Jiang, Wengao] Chongqing Med Univ, Sch Pharm, Key Lab Mol & Biochem Pharmacol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Jiang, WA (通讯作者)，Chongqing Med Univ, Sch Pharm, Key Lab Mol & Biochem Pharmacol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：EXPERIMENTAL NEUROLOGY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000910586600001

JCR分区：Q1

影响因子：5.3

年份：2023

卷号：361

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Major depressive disorder (MDD); Chronic unpredicted stress (CUS); Receptor for advanced glycation end-products; (RAGE); NMDA receptor subtype 2A (NR2A); NMDA receptor subtype 2B (NR2B); hippocampus; Dentate gyrus (DG)

摘要："NMDA receptors play pivotal roles in the neurobiology of chronic stress-induced mood disorders. But the mechanism for chronic stress to disturb the expression of NMDA receptor subunits is still unclear. Recent re-searches indicated the involvement RAGE signaling pathway in regulation of glutamate system functions. In this study, we hypothesized RAGE signaling pathway mediated chronic stress-induced alteration in the expression of NMDA receptor subunits, leading to depressive-like behaviors. CUS decreased the expression of RAGE, NR2A, and NR2B, inhibited the phosphorylation of transcript factor ERK and CREB in rat hippocampus DG. RAGE knockdown in hippocampus DG by RAGE shRNA lentiviral particles induced depressive-like behaviors, reduced the mRNA and protein expression of NR2A and NR2B, and inhibited the phosphorylation of ERK and CREB. RAGE over-expression in hippocampus DG by RAGE adenovirus particles reversed the effects of CUS on depressive-like behaviors, ERK and CREB phosphorylation, and NR2A and NR2B expression. Our findings sug-gests that RAGE signaling pathway at least partially participates in the regulation of NR2A and NR2B expression, which mediates the effects of chronic stress on the depressive-like behaviors. These data provide evidence for RAGE signaling as a possible new pathway through which chronic stress results in the maladaptation of NMDA receptors."

基金机构："National Natural Science Foundation of China; Young Research Fellowship of School of Pharmacy, Chongqing Medical University; CQMU Program for Youth Innovation in Future Medicine; [31600827]; [YXY2019XSGG1]; [W0067]"

基金资助正文："The study was supported by the National Natural Science Foundation of China (Grant No. 31600827) ; and Young Research Fellowship of School of Pharmacy, Chongqing Medical University (Grant No. YXY2019XSGG1) ; CQMU Program for Youth Innovation in Future Medicine (W0067) ."