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Background <p>Major depressive disorder is one of the main causes of disability worldwide, but its etiopathology remains largely unknown, although several hypotheses have been proposed. Recent studies suggest a potential role for matrix metalloproteinase 9 (MMP-9) in depression, as it is overexpressed in the plasma of depressed patients and normalizes following chronic antidepressant treatment. This study aimed to characterize anxiety and depression-like behaviors in transgenic MMP-9 mice, as well as the expression of different neuroplasticity markers associated with depression, in both sexes.</p> Methods <p>In this study, we characterized the behavioral phenotypes of both MMP-9 knockout and MMP-9-overexpressing male and female mice. Here, we used a battery of tests to assess anxiety (open field, light‒dark box, elevated plus maze, and novelty‒suppressed feeding tests), depressive-like (tail suspension and social interaction tests), and cognitive (T-maze) behaviors.</p> Results <p>MMP-9 knockout female mice displayed increased innate anxiety (open field test), decreased behavioral despair (tail suspension test). Compared with control mice, female MMP-9 knockout mice presented increased levels of different neuroplasticity markers in the hippocampus. With respect to MMP-9-overexpressing mice, females presented decreased innate anxiety (elevated plus maze). Male MMP-9-overexpressing mice presented greater conflict-based anxiety (novelty-suppressed feeding test) than control mice did.</p> Conclusions <p>MMP-9 activity modifies anxiety- and depression-like behaviors, as well as neuroplasticity markers, in female but not in male mice. These findings reinforce the sex differences in the etiopathology of depression.</p>

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Sex differences in the modulation of anxiety- and depression-like behaviors by matrix metalloproteinase-9 expression levels in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月22日

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  • Júlia Senserrich,
  • Elena Castro,
  • Eva Florensa-Zanuy,
  • Álvaro Díaz,
  • Ángel Pazos,
  • Albert Adell,
  • Athina Tzinia,
  • Fuencisla Pilar-Cuéllar

摘要

Background

Major depressive disorder is one of the main causes of disability worldwide, but its etiopathology remains largely unknown, although several hypotheses have been proposed. Recent studies suggest a potential role for matrix metalloproteinase 9 (MMP-9) in depression, as it is overexpressed in the plasma of depressed patients and normalizes following chronic antidepressant treatment. This study aimed to characterize anxiety and depression-like behaviors in transgenic MMP-9 mice, as well as the expression of different neuroplasticity markers associated with depression, in both sexes.

Methods

In this study, we characterized the behavioral phenotypes of both MMP-9 knockout and MMP-9-overexpressing male and female mice. Here, we used a battery of tests to assess anxiety (open field, light‒dark box, elevated plus maze, and novelty‒suppressed feeding tests), depressive-like (tail suspension and social interaction tests), and cognitive (T-maze) behaviors.

Results

MMP-9 knockout female mice displayed increased innate anxiety (open field test), decreased behavioral despair (tail suspension test). Compared with control mice, female MMP-9 knockout mice presented increased levels of different neuroplasticity markers in the hippocampus. With respect to MMP-9-overexpressing mice, females presented decreased innate anxiety (elevated plus maze). Male MMP-9-overexpressing mice presented greater conflict-based anxiety (novelty-suppressed feeding test) than control mice did.

Conclusions

MMP-9 activity modifies anxiety- and depression-like behaviors, as well as neuroplasticity markers, in female but not in male mice. These findings reinforce the sex differences in the etiopathology of depression.