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Rationale <p>Depression is a common psychiatric disorder characterized mainly by low mood, anhedonia, and sleep disturbances. In severe cases, it can lead to suicidal tendencies and behaviors. Chronic stress can induce depressive symptoms in some individuals, while others do not respond from stressful experiences, which may represent an intrinsic mechanism underlying resistance to external stressors. The molecular mechanism underlying this resilience remains elusive.</p> Objectives <p>In this study, the molecular differences in the brains between chronic unpredictable mild stress (CUMS) induced depression-like behaviors (CUMS-susceptible) and resilience behaviors (CUMS-resilience) mice were analyzed based on transcriptome sequencing datasets acquired in our prior published work.</p> Methods <p>We performed GO and KEGG functional analyses of differentially expressed genes (DEGs) in distinct brain regions and validated some DEGs in vivo.</p> Results <p>The results showed significant molecular differences in the ventral tegmental area (VTA), amygdala, nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) of CUMS-susceptible and CUMS-resilience mice. Additionally, analysis of DEGs identified four DEGs (<i>Fgfr3</i>, <i>Prodh</i>, <i>Slco1a4</i>, and <i>Gm15446</i>) in the VTA, amygdala, NAc, and mPFC. This suggested that the molecular differences between CUMS-susceptible and CUMS-resilience mice were region-specific.</p> Conclusions <p>Taken together, our studies have revealed a transcription network between depression-like behaviors and resilience behaviors induced by CUMS, and provide new fundamental insights and potential targets for antidepressants discovery.</p>

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Transcriptional profiling reveals brain region-specific changes in gene expression induced by chronic unpredictable mild stress between stress-susceptible and stress-resilient mice

  • 期刊论文

  • 发表日期：

    2026年5月20日

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  • Xiaoyu Chen,
  • Yi Cao,
  • Xianlong Zhao,
  • Yang Li,
  • Zhenhua Song,
  • Juntao Wang,
  • Dong Pan

摘要

Rationale

Depression is a common psychiatric disorder characterized mainly by low mood, anhedonia, and sleep disturbances. In severe cases, it can lead to suicidal tendencies and behaviors. Chronic stress can induce depressive symptoms in some individuals, while others do not respond from stressful experiences, which may represent an intrinsic mechanism underlying resistance to external stressors. The molecular mechanism underlying this resilience remains elusive.

Objectives

In this study, the molecular differences in the brains between chronic unpredictable mild stress (CUMS) induced depression-like behaviors (CUMS-susceptible) and resilience behaviors (CUMS-resilience) mice were analyzed based on transcriptome sequencing datasets acquired in our prior published work.

Methods

We performed GO and KEGG functional analyses of differentially expressed genes (DEGs) in distinct brain regions and validated some DEGs in vivo.

Results

The results showed significant molecular differences in the ventral tegmental area (VTA), amygdala, nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) of CUMS-susceptible and CUMS-resilience mice. Additionally, analysis of DEGs identified four DEGs (Fgfr3, Prodh, Slco1a4, and Gm15446) in the VTA, amygdala, NAc, and mPFC. This suggested that the molecular differences between CUMS-susceptible and CUMS-resilience mice were region-specific.

Conclusions

Taken together, our studies have revealed a transcription network between depression-like behaviors and resilience behaviors induced by CUMS, and provide new fundamental insights and potential targets for antidepressants discovery.