Protective role of TRPV2 in synaptic plasticity through the ERK1/ 2-CREB-BDNF pathway in chronic unpredictable mild stress rats

被引：4

作者：

Zhou, Yitong ^{[1
]}

Cong, Ting ^{[2
]}

Chen, Jun ^{[3
]}

Chu, Zhenchen ^{[4
]}

Sun, Ye ^{[1
]}

Zhao, Danmei ^{[1
]}

Chen, Xue ^{[1
]}

Li, Liya ^{[1
]}

Liu, Yingxin ^{[5
]}

Cheng, Jiani ^{[1
]}

Li, Qiwei ^{[1
]}

Yin, Shengming ^{[5
]}

Xiao, Zhaoyang ^{[1
]}

机构：

[1] Dalian Med Univ, Affliated Hosp 2, Dept Anesthesiol, 467 Zhongshan Rd, Dalian 116027, Liaoning, Peoples R China

[2] Qingdao Univ, Affiliated Hosp, Dept Anesthesiol, Qingdao 266000, Shandong, Peoples R China

[3] Dalian Med Univ, Lab Anim Ctr, Dalian 116044, Liaoning, Peoples R China

[4] Qingdao Municipal Hosp, Dept Orthoped, Qingdao 266011, Shandong, Peoples R China

[5] Dalian Med Univ, Basic Med Coll, Dept Physiol, 9,West Sect,Lvshun South Rd, Dalian 116044, Liaoning, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2024年 / 721卷

基金：

中国国家自然科学基金;

关键词：

Depression; CUMS; TRPV2; Synaptic plasticity; ERK1/2-CREB-BDNF signaling pathway; L-KYNURENINE; BDNF; CREB; ACTIVATION; OUTGROWTH; NEURONS; SYSTEM;

D O I：

10.1016/j.bbrc.2024.150128

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Purpose: Chronic stress is a significant risk factor for mood disorders such as depression, where synaptic plasticity plays a central role in pathogenesis. Transient Receptor Potential Vanilloid Type-2 (TRPV2) Ion Channels are implicated in hypothalamic-pituitary-adrenal axis disorders. Previous proteomic analysis indicated a reduction in TRPV2 levels in the chronic unpredictable mild stress (CUMS) rat model, yet its role in synaptic plasticity during depression remains to be elucidated. This study aims to investigate TRPV2's role in depression and its underlying mechanisms. Methods: In vivo and in vitro experiments were conducted using the TRPV2-specific agonist probenecid and ERK1/2 inhibitors SCH772984. In vivo, rats underwent six weeks of CUMS before probenecid administration. Depressive-like behaviors were assessed through behavioral tests. ELISA kits measured 5-HT, DA, NE levels in rat hippocampal tissues. Hippocampal morphology was examined via Nissl staining. In vitro, rat hippocampal neuron cell lines were treated with ERK1/2 inhibitors SCH772984 and probenecid. Western blot, immunofluorescence, immunohistochemical staining, and RT-qPCR assessed TRPV2 expression, neurogenesis-related proteins, synaptic markers, and ERK1/2-CREB-BDNF signaling proteins. Results: Decreased hippocampal TRPV2 levels were observed in CUMS rats. Probenecid treatment mitigated depressive-like behavior and enhanced hippocampal 5-HT, NE, and DA levels in CUMS rats. TRPV2 activation countered CUMS-induced synaptic plasticity inhibition. Probenecid activated the ERK1/2-CREB-BDNF pathway, suggesting TRPV2's involvement in this pathway via ERK1/2. Conclusion: These findings indicate that TRPV2 activation offers protective effects against depressive-like behaviors and enhances hippocampal synaptic plasticity in CUMS rats via the ERK1/2-CREB-BDNF pathway. TRPV2 emerges as a potential therapeutic target for depression.

引用

页数：11