Scholarlink

Background <p>Emerging evidence suggests a connection between mitophagy-a key mitochondrial quality control mechanism-and depression. Furthermore, sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylase, has been implicated in the pathophysiology of depression, though its precise role remains elusive. This study aimed to investigate how SIRT1 modulates depressive-like behaviors in mice and to determine whether mitophagy mediates this process.</p> Methods <p>Male BALB/c mice were administered lipopolysaccharide (LPS) to mimic depressive-like behaviors. The treatment group received a pre-administration of SRT1720 (50&#xa0;mg/kg, i.p.), a specific SIRT1 activator. Depressive-like behaviors were assessed by sucrose preference test (SPT) and forced swimming test (FST). Additionally, hippocampal neuronal and mitochondrial ultrastructure was detected via transmission electron microscopy (TEM), and mitophagy-related protein expression was examined by western blotting.</p> Results <p>Results demonstrated that activation of SIRT1 significantly mitigated LPS-induced depressive-like behaviors in mice. Moreover, it was observed that SIRT1 activation protected against LPS-induced neuronal and mitochondrial damage in the hippocampus. TEM analysis revealed a marked increase in hippocampal autophagosomes following SIRT1 activation, accompanied by significantly elevated expression of LC3II and Parkin, suggesting enhanced mitophagy. In vitro experiment using HT-22 cells provided additional evidence that SIRT1 activation ameliorated LPS-induced mitochondrial dysfunction and promoted mitophagy via Parkin-mediated pathway.</p> Conclusions <p>These findings suggested that activation of SIRT1 could alleviate depressive-like behaviors in mice following LPS challenge, potentially through a Parkin-dependent mitophagy mechanism.</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

SRT1720 ameliorates LPS-induced depressive-like behaviors in mice and activates Parkin-mediated mitophagy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月30日

查看全文
  • Luna Sun,
  • Chaoran Li,
  • Jianli Shi,
  • Wenfeng Zeng,
  • Lingling Wu,
  • Shunlun Wan,
  • Yunxia Wang

摘要

Background

Emerging evidence suggests a connection between mitophagy-a key mitochondrial quality control mechanism-and depression. Furthermore, sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylase, has been implicated in the pathophysiology of depression, though its precise role remains elusive. This study aimed to investigate how SIRT1 modulates depressive-like behaviors in mice and to determine whether mitophagy mediates this process.

Methods

Male BALB/c mice were administered lipopolysaccharide (LPS) to mimic depressive-like behaviors. The treatment group received a pre-administration of SRT1720 (50 mg/kg, i.p.), a specific SIRT1 activator. Depressive-like behaviors were assessed by sucrose preference test (SPT) and forced swimming test (FST). Additionally, hippocampal neuronal and mitochondrial ultrastructure was detected via transmission electron microscopy (TEM), and mitophagy-related protein expression was examined by western blotting.

Results

Results demonstrated that activation of SIRT1 significantly mitigated LPS-induced depressive-like behaviors in mice. Moreover, it was observed that SIRT1 activation protected against LPS-induced neuronal and mitochondrial damage in the hippocampus. TEM analysis revealed a marked increase in hippocampal autophagosomes following SIRT1 activation, accompanied by significantly elevated expression of LC3II and Parkin, suggesting enhanced mitophagy. In vitro experiment using HT-22 cells provided additional evidence that SIRT1 activation ameliorated LPS-induced mitochondrial dysfunction and promoted mitophagy via Parkin-mediated pathway.

Conclusions

These findings suggested that activation of SIRT1 could alleviate depressive-like behaviors in mice following LPS challenge, potentially through a Parkin-dependent mitophagy mechanism.