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<p>Affective empathy describes the capacity to share others’ emotions, yet the molecular mechanisms governing individual differences in empathic sensitivity remain poorly understood. Using a male mouse model of social transmission of depression (STD), we demonstrated that STD‑sensitive observer mice exhibit heightened neuronal excitability and upregulated major urinary protein 1 (MUP1) expression in the medial prefrontal cortex (mPFC) compared with STD‑insensitive observer mice. Mechanistically, MUP1 drives the STD‑sensitive phenotype by modulating astrocytic glutamate transporter 1 (GLT1) to augment mPFC neuronal excitability. Via virtual screening, we identified two small‑molecule compounds (C25 and C11) that bidirectionally modulate STD‑related behaviors. In summary, our work establishes MUP1 as a master modulator of STD vulnerability, deciphers mechanisms driving heterogeneous affective empathy across individuals, and unveils actionable therapeutic candidates for empathy-related psychiatric illnesses.</p>

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Major urinary protein 1 modulates neuronal excitability in the medial prefrontal cortex in a male mouse model of affective empathy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月17日

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  • Kun Zhang,
  • Dake Song,
  • Yingying Zhang,
  • Le Yang,
  • Ban Feng,
  • Ruixia Liu,
  • Hengxin Gong,
  • Longbiao Cui,
  • Shanbo Ma,
  • Yanwei Chen,
  • Min Wang,
  • Xinshang Wang,
  • Yumei Wu,
  • Ting Bai,
  • Kun Xia,
  • Minggao Zhao,
  • Shuibing Liu

摘要

Affective empathy describes the capacity to share others’ emotions, yet the molecular mechanisms governing individual differences in empathic sensitivity remain poorly understood. Using a male mouse model of social transmission of depression (STD), we demonstrated that STD‑sensitive observer mice exhibit heightened neuronal excitability and upregulated major urinary protein 1 (MUP1) expression in the medial prefrontal cortex (mPFC) compared with STD‑insensitive observer mice. Mechanistically, MUP1 drives the STD‑sensitive phenotype by modulating astrocytic glutamate transporter 1 (GLT1) to augment mPFC neuronal excitability. Via virtual screening, we identified two small‑molecule compounds (C25 and C11) that bidirectionally modulate STD‑related behaviors. In summary, our work establishes MUP1 as a master modulator of STD vulnerability, deciphers mechanisms driving heterogeneous affective empathy across individuals, and unveils actionable therapeutic candidates for empathy-related psychiatric illnesses.