Scholarlink

<p>Depression associated with peripheral inflammation is characterized by severe symptoms and high relapse rates, highlighting the urgent need for rapid-acting antidepressants. Here, we demonstrate that muscone, the principal bioactive component of musk, exerts rapid antidepressant effects in murine models of peripheral inflammation-induced depression [lipopolysaccharide (LPS) challenge; dextran sulfate sodium-induced colitis] rather than in chronic restraint stress-induced depression. Acute muscone administration did not possess innate anti-inflammatory activity but selectively suppressed the hyperactivation of glutamatergic neurons within the anterior cingulate cortex (ACC), a crucial mood-regulatory hub. Chemogenetic activation or inhibition of ACC glutamatergic neurons abolished or mimicked the anti-depressive behavioral effects of muscone. Mechanistically, muscone induced presynaptic inhibition of excitatory transmission in ACC glutamatergic neurons through activation of the cannabinoid CB1 receptor. These findings identify muscone as a promising rapid-onset therapeutic candidate for treating inflammation-associated depression.</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

Muscone Exerts Rapid Antidepressant Effects Through Modulating Glutamatergic Neural Transmission in the Anterior Cingulate Cortex Against Peripheral Inflammation-induced Depression

  • 期刊论文

  • 发表日期：

    2026年5月21日

查看全文
  • Xiaoyun Qiu,
  • Xiaojie Zhang,
  • Yuanzhi Yang,
  • Minjuan Sun,
  • Xiaoli Da,
  • Jiaying Liu,
  • Rui Wang,
  • Jingjia Liang,
  • Xuhong Jiang,
  • Gang Tian,
  • Qiyuan Shan,
  • Yu Du,
  • Lihong Li,
  • Li Cheng,
  • Yi Wang,
  • Zhong Chen,
  • Cenglin Xu

摘要

Depression associated with peripheral inflammation is characterized by severe symptoms and high relapse rates, highlighting the urgent need for rapid-acting antidepressants. Here, we demonstrate that muscone, the principal bioactive component of musk, exerts rapid antidepressant effects in murine models of peripheral inflammation-induced depression [lipopolysaccharide (LPS) challenge; dextran sulfate sodium-induced colitis] rather than in chronic restraint stress-induced depression. Acute muscone administration did not possess innate anti-inflammatory activity but selectively suppressed the hyperactivation of glutamatergic neurons within the anterior cingulate cortex (ACC), a crucial mood-regulatory hub. Chemogenetic activation or inhibition of ACC glutamatergic neurons abolished or mimicked the anti-depressive behavioral effects of muscone. Mechanistically, muscone induced presynaptic inhibition of excitatory transmission in ACC glutamatergic neurons through activation of the cannabinoid CB1 receptor. These findings identify muscone as a promising rapid-onset therapeutic candidate for treating inflammation-associated depression.