Scholarlink

<p>Translocator protein (18&#xa0;kDa) (TSPO) has been implicated in the development of depression and cognitive dysfunction. This study aimed to investigate the anti-depression/anti-anxiety and cognitive enhancing impacts and potential mechanisms of TSPO ligand YL-IPA08 in lipopolysaccharide (LPS)-induced inflammatory model. The effects of YL-IPA08 in LPS induced mice were identified by behavioral tests, and the target of YL-IPA08 was validated using the TSPO antagonist PK11195. The microglia in PFC were analyzed by immunofluorescence, and the inflammatory cytokines (IL-6, IL-1β and TNF-α) and anti-inflammatory factors (IL-4, IL-10, TGF-β1) in PFC was detected by ELISA or WB. Effect of TGF-β1 inhibitor Repsox on the actions of YL-IPA08 in LPS-treated mice was further verified. We found that YL-IPA08 administration ameliorated LPS-induced depression/anxiety-like behaviors and cognitive impairment, which were blocked by PK11195. YL-IPA08 reversed the increased number and inflammatory morphological changes of microglia in PFC of LPS mice by targeting TSPO. YL-IPA08 reversed the increased inflammatory cytokines (IL-6, IL-1β and TNF-α) and decreased anti-inflammatory factors (IL-4, IL-10) in the PFC of LPS mice by TSPO activation. In addition, YL-IPA08 elevated the suppressed levels of TGF-β1 and smad3 (member of TGF-β1 pathway) in PFC of LPS mice by TSPO activation. TGF-β1 inhibitor Repsox blocked the anti-depression/anxiety and cognition enhancing effects of YL-IPA08 in LPS mice. Our data implicated that central inflammation regulation and TSPO-TGF-β1/Smad pathway activation contributed to the anti-depressant/anxiety and cognitive promoting impacts of YL-IPA08.</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

The impact and mechanisms of YL-IPA08, a potent ligand for the translocator protein (18 kDa) on protection against LPS-induced depression and cognitive dysfunction in rodents

  • 期刊论文

  • 发表日期：

    2025年3月6日

查看全文
  • Lin-yu Cui,
  • Jing-yao Duan,
  • Jiao-zhao Yan,
  • Jing-ya Wang,
  • Peng Ren,
  • Li-ming Zhang,
  • Wen-zhi Guo,
  • Wei Dai,
  • Yun-feng Li

摘要

Translocator protein (18 kDa) (TSPO) has been implicated in the development of depression and cognitive dysfunction. This study aimed to investigate the anti-depression/anti-anxiety and cognitive enhancing impacts and potential mechanisms of TSPO ligand YL-IPA08 in lipopolysaccharide (LPS)-induced inflammatory model. The effects of YL-IPA08 in LPS induced mice were identified by behavioral tests, and the target of YL-IPA08 was validated using the TSPO antagonist PK11195. The microglia in PFC were analyzed by immunofluorescence, and the inflammatory cytokines (IL-6, IL-1β and TNF-α) and anti-inflammatory factors (IL-4, IL-10, TGF-β1) in PFC was detected by ELISA or WB. Effect of TGF-β1 inhibitor Repsox on the actions of YL-IPA08 in LPS-treated mice was further verified. We found that YL-IPA08 administration ameliorated LPS-induced depression/anxiety-like behaviors and cognitive impairment, which were blocked by PK11195. YL-IPA08 reversed the increased number and inflammatory morphological changes of microglia in PFC of LPS mice by targeting TSPO. YL-IPA08 reversed the increased inflammatory cytokines (IL-6, IL-1β and TNF-α) and decreased anti-inflammatory factors (IL-4, IL-10) in the PFC of LPS mice by TSPO activation. In addition, YL-IPA08 elevated the suppressed levels of TGF-β1 and smad3 (member of TGF-β1 pathway) in PFC of LPS mice by TSPO activation. TGF-β1 inhibitor Repsox blocked the anti-depression/anxiety and cognition enhancing effects of YL-IPA08 in LPS mice. Our data implicated that central inflammation regulation and TSPO-TGF-β1/Smad pathway activation contributed to the anti-depressant/anxiety and cognitive promoting impacts of YL-IPA08.