Scholarlink

<p>Rheumatoid arthritis with depressive symptoms is frequently encountered in clinic. In this study, we investigated the molecular mechanisms responsible for comorbid depression with rheumatoid arthritis in collagen-induced arthritis (CIA) model mice. We showed that depression-like behaviors were developed at 5 weeks after establishing CIA model. Furthermore, we found that in the hippocampus of CIA mice, G-protein coupled receptor kinase 2 (GRK2) was significantly upregulated, while the expression of its target, corticotropin releasing hormone receptor 1 (CRHR1) was notably decreased, as was the downstream cAMP/PKA/CREB/BDNF signaling. We demonstrated that GRK2 could directly interact with CRHR1, suppressing CRHR1-dependent signaling. Knockdown of hippocampal GRK2 or pharmacological inhibition with CP-25 (35 mg·kg<sup>−1</sup>·d<sup>−1</sup>, i.g. for 21 days) could alleviate the depression-like behaviors in CIA mice, whereas GRK2 overexpression induced depression-like behaviors in naive mice. Our study identifies hippocampal GRK2 as a regulator of depression-like behaviors associated with rheumatoid arthritis in CIA model mice, suggesting both a therapeutic target and potential treatment strategy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

G-protein coupled receptor kinase 2 mediates rheumatoid arthritis-induced depression-like behaviors via the hippocampal CRHR1 signaling pathway

  • 期刊论文

  • 发表日期：

    2025年7月21日

查看全文
  • Qian Meng,
  • Meng-hui Guo,
  • Rui Zhang,
  • Jing Wei,
  • Qian Chen,
  • Xue-chun Zhao,
  • Cai-qi Xu,
  • Yao-yao Wu,
  • Jia-jie Kuai,
  • Jie-min Zhao,
  • Yu-jing Wu,
  • Chong-huan Ye,
  • Hong-rui Wei,
  • Xia Zhu,
  • Yan Jin,
  • Zhi Zhang,
  • Wei Wei

摘要

Rheumatoid arthritis with depressive symptoms is frequently encountered in clinic. In this study, we investigated the molecular mechanisms responsible for comorbid depression with rheumatoid arthritis in collagen-induced arthritis (CIA) model mice. We showed that depression-like behaviors were developed at 5 weeks after establishing CIA model. Furthermore, we found that in the hippocampus of CIA mice, G-protein coupled receptor kinase 2 (GRK2) was significantly upregulated, while the expression of its target, corticotropin releasing hormone receptor 1 (CRHR1) was notably decreased, as was the downstream cAMP/PKA/CREB/BDNF signaling. We demonstrated that GRK2 could directly interact with CRHR1, suppressing CRHR1-dependent signaling. Knockdown of hippocampal GRK2 or pharmacological inhibition with CP-25 (35 mg·kg−1·d−1, i.g. for 21 days) could alleviate the depression-like behaviors in CIA mice, whereas GRK2 overexpression induced depression-like behaviors in naive mice. Our study identifies hippocampal GRK2 as a regulator of depression-like behaviors associated with rheumatoid arthritis in CIA model mice, suggesting both a therapeutic target and potential treatment strategy.