@article{10902/37474,
year = {2025},
url = {https://hdl.handle.net/10902/37474},
abstract = {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 depressio},
organization = {This research was funded by the Ministerio de Ciencia, Innovación y
Universidades (RTI2018-097534-B-I00), Centro de Investigación Biomédica en
Red de Salud Mental (CIBERSAM), the Instituto de Salud Carlos III (FIS Grant
PI19-00170), which were co-funded by the European Regional Development
Fund (‘A way to build Europe’), and the Spanish Network for Stress Research
RED2022-134191-T financed by MCIN/AEI/10.13039/501100011033.},
publisher = {Biology of Sex Differences, 2025, 16(1), 34},
title = {Sex differences in the modulation of anxiety- and depression-like behaviors by matrix metalloproteinase-9 expression levels in mice.},
author = {Senserrich Guerrero, Julia and Castro Fernández, María Elena and Florensa Zanuy, Eva Ariadna and Díaz Martínez, Álvaro Marcelino and Pazos Carro, Ángel and Adell Calduch, Albert and Tzinia, Athina and Pilar Cuéllar, María Fuencisla},
}