Sex differences in the modulation of anxiety- and depression-like behaviors by matrix metalloproteinase-9 expression levels in mice
Year: 2025
Type: article
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 depression.
Source: Biology of Sex Differences
Institutions: Universidad de Cantabria, Consejo Superior de Investigaciones Científicas, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Biomedicina y Biotecnología de Cantabria, Sodercan, National Centre of Scientific Research "Demokritos", Institute of Biosciences & Applications
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,290
Awards: G1105844351, G1175115578, G1341303, G1622782223, G2262748287, G2672435700, G300979063, G34346518, G3480869486, G410571670, G425668148, G451917667, G491712853, G5080475149, Receptores AMPA como nuevas dianas moleculares para la obtención de antidepresivos de acción rápida, G5300412236, G5404395142, G5432654084, G5539308778, G5967599077, G624877701, G6298273575, G7084143925, G7805626310, G7863371703, G8181105605, G8497050386, G8696694383, G929308097
OpenAlex ID: W4410587990