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Background <p>The primary protein components of white matter include myelin basic protein (MBP) and 2’,3’-cyclic nucleotide 3’-phosphodiesterase (CNP). Alterations in their expression are significantly implicated in depression. This study investigated changes in MBP and CNP expression associated with depressive-like behaviors induced by chronic unpredictable stress (CUS) and evaluated therapeutic interventions using fluoxetine (FLU), an enriched environment (EE), or their combination.</p> Methods <p>Male Sprague Dawley rats were randomly assigned to a control group and four CUS-exposed groups undergoing 6 weeks of stress. During the final 3 weeks of CUS, rats received daily fluoxetine (CUS + FLU group), were housed in EE (CUS + EE group), or received combined EE and fluoxetine (CUS + FLU + EE group). Depression-like behaviors were assessed through sucrose preference, forced swimming, and open field tests after CUS completion and at the end of weeks 4–6. Protein and mRNA expression levels of MBP and CNP in the prefrontal cortex were quantified via immunohistochemistry, western blot, and qRT-PCR.</p> Results <p>Three weeks following CUS exposure, rats demonstrated significant depression-like behavioral phenotypes. By the fifth week, these behavioral deficits were ameliorated in the CUS + FLU + EE, whereas the CUS + FLU and CUS + EE groups exhibited comparable behavioral recovery by week 6. Parallel molecular analyses revealed diminished protein and mRNA expression levels of MBP and CNP in the prefrontal cortex of CUS-exposed animals, accompanied by a pronounced elevation in IL-1β expression. Therapeutic interventions with FLU, EE, or their combination significantly attenuated these CUS-induced molecular alterations.</p> Conclusions <p>The antidepressant effects correlated with restored MBP, CNP, and IL-1β expression levels, suggesting that MBP/CNP deficiencies in depression may involve IL-1β elevation. In particular, combined enriched environment and fluoxetine accelerated behavioral recovery.</p>

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Combined enriched environment and fluoxetine enhance myelin protein expression in the prefrontal cortex of a chronic unpredictable stress depression model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月11日

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  • Jingyang Gu,
  • Cong Liu,
  • Yan Li,
  • Laipeng Feng,
  • Mengjun Geng,
  • Jiao Dong,
  • Jinhong Han,
  • Liqin Zhao,
  • Qiujing Shao,
  • Hui-Ying Wang,
  • Chang-Hong Wang

摘要

Background

The primary protein components of white matter include myelin basic protein (MBP) and 2’,3’-cyclic nucleotide 3’-phosphodiesterase (CNP). Alterations in their expression are significantly implicated in depression. This study investigated changes in MBP and CNP expression associated with depressive-like behaviors induced by chronic unpredictable stress (CUS) and evaluated therapeutic interventions using fluoxetine (FLU), an enriched environment (EE), or their combination.

Methods

Male Sprague Dawley rats were randomly assigned to a control group and four CUS-exposed groups undergoing 6 weeks of stress. During the final 3 weeks of CUS, rats received daily fluoxetine (CUS + FLU group), were housed in EE (CUS + EE group), or received combined EE and fluoxetine (CUS + FLU + EE group). Depression-like behaviors were assessed through sucrose preference, forced swimming, and open field tests after CUS completion and at the end of weeks 4–6. Protein and mRNA expression levels of MBP and CNP in the prefrontal cortex were quantified via immunohistochemistry, western blot, and qRT-PCR.

Results

Three weeks following CUS exposure, rats demonstrated significant depression-like behavioral phenotypes. By the fifth week, these behavioral deficits were ameliorated in the CUS + FLU + EE, whereas the CUS + FLU and CUS + EE groups exhibited comparable behavioral recovery by week 6. Parallel molecular analyses revealed diminished protein and mRNA expression levels of MBP and CNP in the prefrontal cortex of CUS-exposed animals, accompanied by a pronounced elevation in IL-1β expression. Therapeutic interventions with FLU, EE, or their combination significantly attenuated these CUS-induced molecular alterations.

Conclusions

The antidepressant effects correlated with restored MBP, CNP, and IL-1β expression levels, suggesting that MBP/CNP deficiencies in depression may involve IL-1β elevation. In particular, combined enriched environment and fluoxetine accelerated behavioral recovery.