{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:35:48Z","timestamp":1792046148368,"version":"4.4.0"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTI2018-097534-B-I00"],"award-info":[{"award-number":["RTI2018-097534-B-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Network for Stress Research","award":["RED2022-134191-T"],"award-info":[{"award-number":["RED2022-134191-T"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19-00170"],"award-info":[{"award-number":["PI19-00170"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Sex Differ"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats: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\u2012dark box, elevated plus maze, and novelty\u2012suppressed feeding tests), depressive-like (tail suspension and social interaction tests), and cognitive (T-maze) behaviors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13293-025-00716-5","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T06:00:37Z","timestamp":1747893637000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sex differences in the modulation of anxiety- and depression-like behaviors by matrix metalloproteinase-9 expression levels in mice"],"prefix":"10.1186","volume":"16","author":[{"given":"J\u00falia","family":"Senserrich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Florensa-Zanuy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Pazos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Adell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athina","family":"Tzinia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuencisla","family":"Pilar-Cu\u00e9llar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"716_CR1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association. Task DSM-5Force. Diagnostic and statistical manual of mental disorders: DSM\u20105\u2122. 5th ed. American Psychiatric Publishing, Inc.; 2013.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"716_CR2","unstructured":"WHO. Depressive disorder (depression). 2023. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/depression. Accessed 5 Sep 2024."},{"key":"716_CR3","unstructured":"WHO. COVID-19 pandemic triggers 25% increase in prevalence of anxiety and depression worldwide. 2022. https:\/\/www.who.int\/news\/item\/02-03-2022-covid-19-pandemic-triggers-25-increase-in-prevalence-of-anxiety-and-depression-worldwide. Accessed 5 Sep 2024."},{"key":"716_CR4","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.122.5.509","author":"JJ Schildkraut","year":"1965","unstructured":"Schildkraut JJ. The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry. 1965. https:\/\/doi.org\/10.1176\/ajp.122.5.509","journal-title":"Am J Psychiatry"},{"key":"716_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/cddiscovery.2017.36","author":"Y Xie","year":"2017","unstructured":"Xie Y, Mustafa A, Yerzhan A, Merzhakupova D, Yerlan P, Orakov N. Nuclear matrix metalloproteinases: functions resemble the evolution from the intracellular to the extracellular compartment. Cell Death Discov. 2017. https:\/\/doi.org\/10.1038\/cddiscovery.2017.36","journal-title":"Cell Death Discov"},{"key":"716_CR6","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051076","author":"H Laronha","year":"2020","unstructured":"Laronha H, Caldeira J. Structure and function of human matrix metalloproteinases. Cells. 2020. https:\/\/doi.org\/10.3390\/cells9051076","journal-title":"Cells"},{"key":"716_CR7","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13415","author":"B Vafadari","year":"2016","unstructured":"Vafadari B, Salamian A, Kaczmarek L. MMP-9 in translation: from molecule to brain physiology, pathology, and therapy. J Neurochem. 2016. https:\/\/doi.org\/10.1111\/jnc.13415","journal-title":"J Neurochem"},{"key":"716_CR8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5346-08.2009","author":"P Michaluk","year":"2009","unstructured":"Michaluk P, Mikasova L, Groc L, Frischknecht R, Choquet D, Kaczmarek L. Matrix metalloproteinase-9 controls NMDA receptor surface diffusion through integrin beta1 signaling. J Neurosci. 2009. https:\/\/doi.org\/10.1523\/JNEUROSCI.5346-08.2009","journal-title":"J Neurosci"},{"key":"716_CR9","doi-asserted-by":"publisher","DOI":"10.20388\/OMP2016.002.0027","author":"L Kaczmarek","year":"2016","unstructured":"Kaczmarek L. MMP-9 in control of synaptic plasticity: a subjective account. Opera Med Physiol. 2016. https:\/\/doi.org\/10.20388\/OMP2016.002.0027.","journal-title":"Opera Med Physiol"},{"key":"716_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402141","author":"P Michaluk","year":"2007","unstructured":"Michaluk P, Kaczmarek L. Matrix metalloproteinase-9 in glutamate-dependent adult brain function and dysfunction. Cell Death Differ. 2007. https:\/\/doi.org\/10.1038\/sj.cdd.4402141","journal-title":"Cell Death Differ"},{"key":"716_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2007.11.001","author":"E Milward","year":"2008","unstructured":"Milward E, Kim KJ, Szklarczyk A, Nguyen T, Melli G, Nayak M, et al. Cleavage of Myelin associated glycoprotein by matrix metalloproteinases. J Neuroimmunol. 2008. https:\/\/doi.org\/10.1016\/j.jneuroim.2007.11.001","journal-title":"J Neuroimmunol"},{"key":"716_CR12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009166","author":"E Domenici","year":"2010","unstructured":"Domenici E, Will\u00e9 DR, Tozzi F, Prokopenko I, Miller S, McKeown A, et al. Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections. PLoS ONE. 2010. https:\/\/doi.org\/10.1371\/journal.pone.0009166","journal-title":"PLoS ONE"},{"key":"716_CR13","doi-asserted-by":"publisher","DOI":"10.12659\/msm.895978","author":"K Bobi\u0144ska","year":"2016","unstructured":"Bobi\u0144ska K, Szemraj J, Czarny P, Ga\u0142ecki P. Expression and activity of metalloproteinases in depression. Med Sci Monit. 2016. https:\/\/doi.org\/10.12659\/msm.895978","journal-title":"Med Sci Monit"},{"key":"716_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2016.03.068","author":"K Bobi\u0144ska","year":"2016","unstructured":"Bobi\u0144ska K, Szemraj J, Czarny P, Ga\u0142ecki P. Role of MMP-2, MMP-7, MMP-9 and TIMP-2 in the development of recurrent depressive disorder. J Affect Disord. 2016. https:\/\/doi.org\/10.1016\/j.jad.2016.03.068","journal-title":"J Affect Disord"},{"key":"716_CR15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042676","author":"T Yoshida","year":"2012","unstructured":"Yoshida T, Ishikawa M, Niitsu T, Nakazato M, Watanabe H, Shiraishi T, et al. Decreased serum levels of mature brain-derived neurotrophic factor (BDNF), but not its precursor ProBDNF, in patients with major depressive disorder. PLoS ONE. 2012. https:\/\/doi.org\/10.1371\/journal.pone.0042676","journal-title":"PLoS ONE"},{"key":"716_CR16","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyw019","author":"C Shibasaki","year":"2016","unstructured":"Shibasaki C, Takebayashi M, Itagaki K, Abe H, Kajitani N, Okada-Tsuchioka M, et al. Altered serum levels of matrix Metalloproteinase-2, -9 in response to electroconvulsive therapy for mood disorders. Int J Neuropsychopharmacol. 2016. https:\/\/doi.org\/10.1093\/ijnp\/pyw019","journal-title":"Int J Neuropsychopharmacol"},{"key":"716_CR17","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-19-0376","author":"B Che","year":"2019","unstructured":"Che B, Zhong C, Ge J, Li R, Zhu Z, Bu X, et al. Serum matrix Metalloproteinase-9 is associated with depression after acute ischemic stroke. Circ J. 2019. https:\/\/doi.org\/10.1253\/circj.CJ-19-0376","journal-title":"Circ J"},{"key":"716_CR18","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2019.83146","author":"ME Talarowska","year":"2019","unstructured":"Talarowska ME, Kowalczyk M, Maes M, Carvalho A, Su KP, Szemraj J, et al. Immune to happiness - inflammatory process indicators and depressive personality traits. Arch Med Sci. 2019. https:\/\/doi.org\/10.5114\/aoms.2019.83146","journal-title":"Arch Med Sci"},{"key":"716_CR19","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyx086","author":"C Shibasaki","year":"2018","unstructured":"Shibasaki C, Itagaki K, Abe H, Kajitani N, Okada-Tsuchioka M, Takebayashi M. Possible association between serum matrix Metalloproteinase-9 (MMP-9) levels and relapse in depressed patients following electroconvulsive therapy (ECT). Int J Neuropsychopharmacol. 2018. https:\/\/doi.org\/10.1093\/ijnp\/pyx086","journal-title":"Int J Neuropsychopharmacol"},{"key":"716_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110532","author":"M Bijata","year":"2022","unstructured":"Bijata M, B\u0105czy\u0144ska E, M\u00fcller FE, Bijata K, Masternak J, Krzystyniak A, et al. Activation of the 5-HT7 receptor and MMP-9 signaling module in the hippocampal CA1 region is necessary for the development of depressive-like behavior. Cell Rep. 2022. https:\/\/doi.org\/10.1016\/j.celrep.2022.110532","journal-title":"Cell Rep"},{"key":"716_CR21","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2387-19.2020","author":"S Alaiyed","year":"2020","unstructured":"Alaiyed S, McCann M, Mahajan G, Rajkowska G, Stockmeier CA, Kellar KJ, et al. Venlafaxine stimulates an MMP-9-Dependent increase in excitatory\/inhibitory balance in a stress model of depression. J Neurosci. 2020. https:\/\/doi.org\/10.1523\/JNEUROSCI.2387-19.2020","journal-title":"J Neurosci"},{"key":"716_CR22","doi-asserted-by":"publisher","DOI":"10.25259\/JNRP-2022-6-34","author":"K Saravanan","year":"2022","unstructured":"Saravanan K, Keshri N, Nandeesha H, Menon V, Goud AC. Matrixmetalloproteinase-9 gene polymorphism (rs 17576) increases the risk of depressive symptoms in bipolar disorder. J Neurosci Rural Pract. 2022. https:\/\/doi.org\/10.25259\/JNRP-2022-6-34","journal-title":"J Neurosci Rural Pract"},{"key":"716_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.12.030","author":"NW McGregor","year":"2018","unstructured":"McGregor NW, Dimatelis JJ, Van Zyl PJ, Hemmings SMJ, Kinnear C, Russell VA, et al. A translational approach to the genetics of anxiety disorders. Behav Brain Res. 2018. https:\/\/doi.org\/10.1016\/j.bbr.2017.12.030","journal-title":"Behav Brain Res"},{"key":"716_CR24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105572","author":"S J\u00f6nsson","year":"2014","unstructured":"J\u00f6nsson S, Lundberg AK, Jonasson L. Overexpression of MMP-9 and its inhibitors in blood mononuclear cells after myocardial infarction\u2013is it associated with depressive symptomatology? PLoS ONE. 2014. https:\/\/doi.org\/10.1371\/journal.pone.0105572","journal-title":"PLoS ONE"},{"key":"716_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2022.110624","author":"S Breviario","year":"2023","unstructured":"Breviario S, Senserrich J, Florensa-Zanuy E, Garro-Mart\u00ednez E, D\u00edaz \u00c1, Castro E, et al. Brain matrix metalloproteinase-9 activity is altered in the corticosterone mouse model of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2023. https:\/\/doi.org\/10.1016\/j.pnpbp.2022.110624","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"716_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5995","author":"MA van der Kooij","year":"2014","unstructured":"van der Kooij MA, Fantin M, Rejmak E, Grosse J, Zanoletti O, Fournier C, et al. Role for MMP-9 in stress-induced downregulation of nectin-3 in hippocampal CA1 and associated behavioural alterations. Nat Commun. 2014. https:\/\/doi.org\/10.1038\/ncomms5995","journal-title":"Nat Commun"},{"key":"716_CR27","doi-asserted-by":"publisher","DOI":"10.1080\/10253890.2020.1793943","author":"GT Shishkina","year":"2020","unstructured":"Shishkina GT, Bannova AV, Komysheva NP, Dygalo NN. Anxiogenic-like effect of chronic lipopolysaccharide is associated with increased expression of matrix metalloproteinase 9 in the rat amygdala. Stress. 2020. https:\/\/doi.org\/10.1080\/10253890.2020.1793943","journal-title":"Stress"},{"key":"716_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01520-y","author":"AN Tartt","year":"2022","unstructured":"Tartt AN, Mariani MB, Hen R, Mann JJ, Boldrini M. Dysregulation of adult hippocampal neuroplasticity in major depression: pathogenesis and therapeutic implications. Mol Psychiatry. 2022. https:\/\/doi.org\/10.1038\/s41380-022-01520-y","journal-title":"Mol Psychiatry"},{"key":"716_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.171","author":"BS McEwen","year":"2016","unstructured":"McEwen BS, Nasca C, Gray JD. Stress effects on neuronal structure: hippocampus, amygdala, and prefrontal cortex. Neuropsychopharmacology. 2016. https:\/\/doi.org\/10.1038\/npp.2015.171","journal-title":"Neuropsychopharmacology"},{"key":"716_CR30","doi-asserted-by":"publisher","DOI":"10.3758\/s13415-021-00973-y","author":"M Ghasemi","year":"2022","unstructured":"Ghasemi M, Navidhamidi M, Rezaei F, Azizikia A, Mehranfard N. Anxiety and hippocampal neuronal activity: relationship and potential mechanisms. Cogn Affect Behav Neurosci. 2022. https:\/\/doi.org\/10.3758\/s13415-021-00973-y","journal-title":"Cogn Affect Behav Neurosci"},{"key":"716_CR31","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.857293","author":"R Fujii","year":"2022","unstructured":"Fujii R, Watanabe K, Okamoto N, Natsuyama T, Tesen H, Igata R, Konishi Y, Ikenouchi A, Kakeda S, Yoshimura R. Hippocampal volume and plasma Brain-Derived neurotrophic factor levels in patients with depression and healthy controls. Front Mol Neurosci. 2022. https:\/\/doi.org\/10.3389\/fnmol.2022.857293","journal-title":"Front Mol Neurosci"},{"key":"716_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2023.148375","author":"B Liu","year":"2023","unstructured":"Liu B, Du Y, Xu C, Liu Q, Zhang L. Antidepressant effects of repeated s-ketamine administration as NMDAR antagonist: involvement of CaMKII\u03b1 and mTOR signaling in the hippocampus of CUMS mice. Brain Res. 2023. https:\/\/doi.org\/10.1016\/j.brainres.2023.148375","journal-title":"Brain Res"},{"key":"716_CR33","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-018-2186-9","author":"X Sun","year":"2018","unstructured":"Sun X, Li X, Pan R, Xu Y, Wang Q, Song M. Total saikosaponins of Bupleurum Yinchowense reduces depressive, anxiety-like behavior and increases synaptic proteins expression in chronic corticosterine-treated mice. BMC Complement Altern Med. 2018. https:\/\/doi.org\/10.1186\/s12906-018-2186-9","journal-title":"BMC Complement Altern Med"},{"key":"716_CR34","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10153377","author":"A Mosio\u0142ek","year":"2021","unstructured":"Mosio\u0142ek A, Mosio\u0142ek J, Jakima S, Pi\u0119ta A, Szulc A. Effects of antidepressant treatment on neurotrophic factors (BDNF and IGF-1) in patients with major depressive disorder (MDD). J Clin Med. 2021. https:\/\/doi.org\/10.3390\/jcm10153377","journal-title":"J Clin Med"},{"key":"716_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2021.05.008","author":"E Castr\u00e9n","year":"2021","unstructured":"Castr\u00e9n E, Monteggia LM. Brain-Derived neurotrophic factor signaling in depression and antidepressant action. Biol Psychiatry. 2021. https:\/\/doi.org\/10.1016\/j.biopsych.2021.05.008","journal-title":"Biol Psychiatry"},{"key":"716_CR36","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145710001306","author":"C Piubelli","year":"2011","unstructured":"Piubelli C, Vighini M, Math\u00e9 AA, Domenici E, Carboni L. Escitalopram affects cytoskeleton and synaptic plasticity pathways in a rat gene-environment interaction model of depression as revealed by proteomics. Part II: environmental challenge. Int J Neuropsychopharmacol. 2011. https:\/\/doi.org\/10.1017\/S1461145710001306","journal-title":"Int J Neuropsychopharmacol"},{"key":"716_CR37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07637.x","author":"A Fragkouli","year":"2012","unstructured":"Fragkouli A, Papatheodoropoulos C, Georgopoulos S, Stamatakis A, Stylianopoulou F, Tsilibary EC, et al. Enhanced neuronal plasticity and elevated endogenous sAPP\u03b1 levels in mice overexpressing MMP9. J Neurochem. 2012. https:\/\/doi.org\/10.1111\/j.1471-4159.2011.07637.x","journal-title":"J Neurochem"},{"key":"716_CR38","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1100-2","author":"R Vidal","year":"2019","unstructured":"Vidal R, Garro-Mart\u00ednez E, D\u00edaz \u00c1, Castro E, Florensa-Zanuy E, Taketo MM, et al. Targeting \u03b2-Catenin in GLAST-Expressing cells: impact on anxiety and Depression-Related behavior and hippocampal proliferation. Mol Neurobiol. 2019. https:\/\/doi.org\/10.1007\/s12035-018-1100-2","journal-title":"Mol Neurobiol"},{"key":"716_CR39","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr351","author":"A Giralt","year":"2011","unstructured":"Giralt A, Saavedra A, Carret\u00f3n O, Xifr\u00f3 X, Alberch J, P\u00e9rez-Navarro E. Increased PKA signaling disrupts recognition memory and Spatial memory: role in Huntington\u2019s disease. Hum Mol Genet. 2011. https:\/\/doi.org\/10.1093\/hmg\/ddr351","journal-title":"Hum Mol Genet"},{"key":"716_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2011.01.019","author":"JP Guilloux","year":"2011","unstructured":"Guilloux JP, Seney M, Edgar N, Sibille E. Integrated behavioral z-scoring increases the sensitivity and reliability of behavioral phenotyping in mice: relevance to emotionality and sex. J Neurosci Methods. 2011. https:\/\/doi.org\/10.1016\/j.jneumeth.2011.01.019","journal-title":"J Neurosci Methods"},{"key":"716_CR41","doi-asserted-by":"publisher","DOI":"10.1126\/science.1190287","author":"N Li","year":"2010","unstructured":"Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010. https:\/\/doi.org\/10.1126\/science.1190287","journal-title":"Science"},{"key":"716_CR42","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5239-12.2013","author":"E Knapska","year":"2013","unstructured":"Knapska E, Lioudyno V, Kiryk A, Mikosz M, G\u00f3rkiewicz T, Michaluk P, et al. Reward learning requires activity of matrix metalloproteinase-9 in the central amygdala. J Neurosci. 2013. https:\/\/doi.org\/10.1523\/JNEUROSCI.5239-12.2013","journal-title":"J Neurosci"},{"key":"716_CR43","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1162-14.2014","author":"H Sidhu","year":"2014","unstructured":"Sidhu H, Dansie LE, Hickmott PW, Ethell DW, Ethell IM. Genetic removal of matrix metalloproteinase 9 rescues the symptoms of fragile X syndrome in a mouse model. J Neurosci. 2014. https:\/\/doi.org\/10.1523\/JNEUROSCI.1162-14.2014","journal-title":"J Neurosci"},{"key":"716_CR44","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-021-00643-2","author":"C Ringland","year":"2021","unstructured":"Ringland C, Schweig JE, Eisenbaum M, Paris D, Ait-Ghezala G, Mullan M, et al. MMP9 modulation improves specific neurobehavioral deficits in a mouse model of Alzheimer\u2019s disease. BMC Neurosci. 2021. https:\/\/doi.org\/10.1186\/s12868-021-00643-2","journal-title":"BMC Neurosci"},{"key":"716_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2016.08.031","author":"NN Burke","year":"2016","unstructured":"Burke NN, Coppinger J, Deaver DR, Roche M, Finn DP, Kelly J. Sex differences and similarities in depressive- and anxiety-like behaviour in the Wistar-Kyoto rat. Physiol Behav. 2016. https:\/\/doi.org\/10.1016\/j.physbeh.2016.08.031","journal-title":"Physiol Behav"},{"key":"716_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2019.112670","author":"JL Scholl","year":"2019","unstructured":"Scholl JL, Afzal A, Fox LC, Watt MJ, Forster GL. Sex differences in anxiety-like behaviors in rats. Physiol Behav. 2019. https:\/\/doi.org\/10.1016\/j.physbeh.2019.112670","journal-title":"Physiol Behav"},{"key":"716_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2021.173168","author":"P Knight","year":"2021","unstructured":"Knight P, Chellian R, Wilson R, Behnood-Rod A, Panunzio S, Bruijnzeel AW. Sex differences in the elevated plus-maze test and large open field test in adult Wistar rats. Pharmacol Biochem Behav. 2021. https:\/\/doi.org\/10.1016\/j.pbb.2021.173168","journal-title":"Pharmacol Biochem Behav"},{"key":"716_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2008.07.005","author":"A Ramos","year":"2008","unstructured":"Ramos A. Animal models of anxiety: do I need multiple tests? Trends Pharmacol Sci. 2008. https:\/\/doi.org\/10.1016\/j.tips.2008.07.005","journal-title":"Trends Pharmacol Sci"},{"key":"716_CR49","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2021.113288","author":"K Kennedy-Wood","year":"2021","unstructured":"Kennedy-Wood K, Ng CAS, Alaiyed S, Foley PL, Conant K. Increased MMP-9 levels with straindependent stress resilience and tunnel handling in mice. Behav Brain Res. 2021. https:\/\/doi.org\/10.1016\/j.bbr.2021.113288","journal-title":"Behav Brain Res"},{"key":"716_CR50","doi-asserted-by":"publisher","DOI":"10.3390\/cells8091018","author":"S Berger","year":"2019","unstructured":"Berger S, Gureczny S, Reisinger SN, Horvath O, Pollak DD. Effect of chronic corticosterone treatment on Depression-Like behavior and sociability in female and male C57BL\/6 N mice. Cells. 2019. https:\/\/doi.org\/10.3390\/cells8091018","journal-title":"Cells"},{"key":"716_CR51","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.107780","author":"CN Yohn","year":"2019","unstructured":"Yohn CN, Ashamalla SA, Bokka L, Gergues MM, Garino A, Samuels BA. Social instability is an effective chronic stress paradigm for both male and female mice. Neuropharmacology. 2019. https:\/\/doi.org\/10.1016\/j.neuropharm.2019.107780","journal-title":"Neuropharmacology"},{"key":"716_CR52","unstructured":"Florensa Zanuy E. Cannabidiol as a fast-acting antidepressant: identification of the molecular mechanisms implicated in its antidepressant effect. MSc thesis, University of Cantabria. 2021. https:\/\/repositorio.unican.es\/xmlui\/handle\/10902\/21656. Accessed 30 Sep 2024."},{"key":"716_CR53","doi-asserted-by":"publisher","DOI":"10.20945\/2359-3997000000400","author":"FB Lorena","year":"2021","unstructured":"Lorena FB, do Nascimento BPP, Camargo ELRA, Bernardi MM, Fukushima AR, do Panizza N. Long-term obesity is associated with depression and neuroinflammation. Arch Endocrinol Metab. 2021. https:\/\/doi.org\/10.20945\/2359-3997000000400","journal-title":"Arch Endocrinol Metab"},{"key":"716_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2021.04.014","author":"CM Chevalier","year":"2021","unstructured":"Chevalier CM, Krampert L, Schreckenbach M, Schubert CF, Reich J, Novak B, et al. MMP9 mRNA is a potential diagnostic and treatment monitoring marker for PTSD: evidence from mice and humans. Eur Neuropsychopharmacol. 2021. https:\/\/doi.org\/10.1016\/j.euroneuro.2021.04.014","journal-title":"Eur Neuropsychopharmacol"},{"key":"716_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.03.023","author":"Y Gong","year":"2018","unstructured":"Gong Y, Tong L, Yang R, Hu W, Xu X, Wang W, et al. Dynamic changes in hippocampal microglia contribute to depressive-like behaviour induced by early social isolation. Neuropharmacology. 2018. https:\/\/doi.org\/10.1016\/j.neuropharm.2018.03.023","journal-title":"Neuropharmacology"},{"key":"716_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.02.149","author":"F Yang","year":"2020","unstructured":"Yang F, Zhu W, Cai X, Zhang W, Yu Z, Li X, et al. Minocycline alleviates NLRP3 inflammasome-dependent pyroptosis in monosodium glutamate-induced depressive rats. Biochem Biophys Res Commun. 2020. https:\/\/doi.org\/10.1016\/j.bbrc.2020.02.149","journal-title":"Biochem Biophys Res Commun"},{"key":"716_CR57","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01821-4","author":"PM Maras","year":"2022","unstructured":"Maras PM, Hebda-Bauer EK, Hagenauer MH, Hilde KL, Blandino P Jr, Watson SJ Jr, et al. Differences in microglia morphological profiles reflect divergent emotional temperaments: insights from a selective breeding model. Transl Psychiatry. 2022. https:\/\/doi.org\/10.1038\/s41398-022-01821-4","journal-title":"Transl Psychiatry"},{"key":"716_CR58","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2016.07.002","author":"A Kupferberg","year":"2016","unstructured":"Kupferberg A, Bicks L, Hasler G. Social functioning in major depressive disorder. Neurosci Biobehav Rev. 2016. https:\/\/doi.org\/10.1016\/j.neubiorev.2016.07.002","journal-title":"Neurosci Biobehav Rev"},{"key":"716_CR59","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.09.012","author":"R Bhandari","year":"2015","unstructured":"Bhandari R, Kuhad A. Neuropsychopharmacotherapeutic efficacy of Curcumin in experimental paradigm of autism spectrum disorders. Life Sci. 2015. (2015). https:\/\/doi.org\/10.1016\/j.lfs.2015.09.012","journal-title":"Life Sci"},{"key":"716_CR60","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2016.12.012","author":"R Bhandari","year":"2017","unstructured":"Bhandari R, Kuhad A. Resveratrol suppresses neuroinflammation in the experimental paradigm of autism spectrum disorders. Neurochem Int. 2017. https:\/\/doi.org\/10.1016\/j.neuint.2016.12.012","journal-title":"Neurochem Int"},{"key":"716_CR61","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000024581","author":"Y Du","year":"2021","unstructured":"Du Y, Wei J, Yang X, Dou Y, Zhao L, Qi X, et al. Plasma metabolites were associated with Spatial working memory in major depressive disorder. Med (Baltim). 2021. https:\/\/doi.org\/10.1097\/MD.0000000000024581","journal-title":"Med (Baltim)"},{"key":"716_CR62","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.09.093","author":"A Vance","year":"2021","unstructured":"Vance A, Winther J. Spatial working memory performance in children and adolescents with major depressive disorder and dysthymic disorder. J Affect Disord. 2021. https:\/\/doi.org\/10.1016\/j.jad.2020.09.093","journal-title":"J Affect Disord"},{"key":"716_CR63","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2011.1864","author":"P Sherchan","year":"2011","unstructured":"Sherchan P, Lekic T, Suzuki H, Hasegawa Y, Rolland W, Duris K, et al. Minocycline improves functional outcomes, memory deficits, and histopathology after endovascular perforation-induced subarachnoid hemorrhage in rats. J Neurotrauma. 2011. https:\/\/doi.org\/10.1089\/neu.2011.1864","journal-title":"J Neurotrauma"},{"key":"716_CR64","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.03.001","author":"JN Crawley","year":"2008","unstructured":"Crawley JN. Behavioral phenotyping strategies for mutant mice. Neuron. 2008. https:\/\/doi.org\/10.1016\/j.neuron.2008.03.001","journal-title":"Neuron"},{"key":"716_CR65","doi-asserted-by":"publisher","DOI":"10.30802\/AALAS-CM-23-000033","author":"MA Suckow","year":"2023","unstructured":"Suckow MA, Tirado-Mu\u00f1iz N. Seasonal variation of laboratory animals as a consideration for research reproducibility. Comp Med. 2023. https:\/\/doi.org\/10.30802\/AALAS-CM-23-000033","journal-title":"Comp Med"},{"key":"716_CR66","doi-asserted-by":"publisher","DOI":"10.1038\/srep16024","author":"XL Liu","year":"2015","unstructured":"Liu XL, Luo L, Mu RH, Liu BB, Geng D, Liu Q, et al. Fluoxetine regulates mTOR signalling in a region-dependent manner in depression-like mice. Sci Rep. 2015. https:\/\/doi.org\/10.1038\/srep16024","journal-title":"Sci Rep"},{"key":"716_CR67","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.10.008","author":"D Xu","year":"2018","unstructured":"Xu D, Sun Y, Wang C, Wang H, Wang Y, Zhao W, et al. Hippocampal mTOR signaling is required for the antidepressant effects of Paroxetine. Neuropharmacology. 2018. https:\/\/doi.org\/10.1016\/j.neuropharm.2017.10.008","journal-title":"Neuropharmacology"},{"key":"716_CR68","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2019.112708","author":"D Xu","year":"2020","unstructured":"Xu D, Wang C, Zhu X, Zhao W, Jiang B, Cui S, et al. The antidepressant-like effects of fluvoxamine in mice involve the mTOR signaling in the hippocampus and prefrontal cortex. Psychiatry Res. 2020. https:\/\/doi.org\/10.1016\/j.psychres.2019.112708","journal-title":"Psychiatry Res"},{"key":"716_CR69","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9580-9","author":"FL Pazini","year":"2016","unstructured":"Pazini FL, Cunha MP, Rosa JM, Colla AR, Lieberknecht V, Oliveira \u00c1, et al. Creatine, similar to ketamine, counteracts Depressive-Like behavior induced by corticosterone via PI3K\/Akt\/mTOR pathway. Mol Neurobiol. 2016. https:\/\/doi.org\/10.1007\/s12035-015-9580-9","journal-title":"Mol Neurobiol"},{"key":"716_CR70","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-65300-w","author":"RF de Almeida","year":"2020","unstructured":"de Almeida RF, Pocharski CB, Rodrigues ALS, Elisabetsky E, Souza DO. Guanosine fast onset antidepressant-like effects in the olfactory bulbectomy mice model. Sci Rep. 2020. https:\/\/doi.org\/10.1038\/s41598-020-65300-w","journal-title":"Sci Rep"},{"key":"716_CR71","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126416","author":"MK Seo","year":"2022","unstructured":"Seo MK, Lee JA, Jeong S, Seog DH, Lee JG, Park SW. Effects of chronic LY341495 on hippocampal mTORC1 signaling in mice with chronic unpredictable Stress-Induced depression. Int J Mol Sci. 2022. https:\/\/doi.org\/10.3390\/ijms23126416","journal-title":"Int J Mol Sci."},{"key":"716_CR72","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-020-05469-0","author":"Y Yao","year":"2020","unstructured":"Yao Y, Ju P, Liu H, Wu X, Niu Z, Zhu Y, et al. Ifenprodil rapidly ameliorates depressive-like behaviors, activates mTOR signaling and modulates Proinflammatory cytokines in the hippocampus of CUMS rats. Psychopharmacology. 2020. https:\/\/doi.org\/10.1007\/s00213-020-05469-0","journal-title":"Psychopharmacology"},{"key":"716_CR73","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2015.00106","author":"KL Janke","year":"2015","unstructured":"Janke KL, Cominski TP, Kuzhikandathil EV, Servatius RJ, Pang KC. Investigating the role of hippocampal BDNF in anxiety vulnerability using classical eyeblink conditioning. Front Psychiatry. 2015. https:\/\/doi.org\/10.3389\/fpsyt.2015.00106","journal-title":"Front Psychiatry"},{"key":"716_CR74","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-01187-5","author":"M Koehl","year":"2021","unstructured":"Koehl M, Ladev\u00e8ze E, Catania C, Cota D, Abrous DN. Inhibition of mTOR signaling by genetic removal of p70 S6 kinase 1 increases anxiety-like behavior in mice. Transl Psychiatry. 2021. https:\/\/doi.org\/10.1038\/s41398-020-01187-5","journal-title":"Transl Psychiatry"},{"key":"716_CR75","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2445com","author":"J Esparza","year":"2004","unstructured":"Esparza J, Kruse M, Lee J, Michaud M, Madri JA. MMP-2 null mice exhibit an early onset and severe experimental autoimmune encephalomyelitis due to an increase in MMP-9 expression and activity. FASEB J. 2004. https:\/\/doi.org\/10.1096\/fj.04-2445com","journal-title":"FASEB J"},{"key":"716_CR76","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.06.021","author":"A Fragkouli","year":"2014","unstructured":"Fragkouli A, Tsilibary EC, Tzinia AK. Neuroprotective role of MMP-9 overexpression in the brain of Alzheimer\u2019s 5xFAD mice. Neurobiol Dis. 2014. https:\/\/doi.org\/10.1016\/j.nbd.2014.06.021","journal-title":"Neurobiol Dis"},{"key":"716_CR77","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2012.07.019","author":"JK Rybakowski","year":"2013","unstructured":"Rybakowski JK, Remlinger-Molenda A, Czech-Kucharska A, Wojcicka M, Michalak M, Losy J. Increased serum matrix metalloproteinase-9 (MMP-9) levels in young patients during bipolar depression. J Affect Disord. 2013. https:\/\/doi.org\/10.1016\/j.jad.2012.07.019","journal-title":"J Affect Disord"},{"key":"716_CR78","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2018.02.003","author":"A Floriou-Servou","year":"2018","unstructured":"Floriou-Servou A, von Ziegler L, Stalder L, Sturman O, Privitera M, Rassi A, Cremonesi A, Th\u00f6ny B, Bohacek J. Distinct proteomic, transcriptomic, and epigenetic stress responses in dorsal and ventral Hippocampus. Biol Psychiatry. 2018. https:\/\/doi.org\/10.1016\/j.biopsych.2018.02.003","journal-title":"Biol Psychiatry"}],"container-title":["Biology of Sex Differences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13293-025-00716-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13293-025-00716-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13293-025-00716-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T06:00:45Z","timestamp":1747893645000},"score":1,"resource":{"primary":{"URL":"https:\/\/bsd.biomedcentral.com\/articles\/10.1186\/s13293-025-00716-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,22]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["716"],"URL":"https:\/\/doi.org\/10.1186\/s13293-025-00716-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-5820273\/v1","asserted-by":"object"}]},"ISSN":["2042-6410"],"issn-type":[{"value":"2042-6410","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,22]]},"assertion":[{"value":"13 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures were carried out with the previous approval of the Animal Care Committee of the University of Cantabria and according to Spanish legislation (RD 53\/2013) and the European Communities Council Directive on \u201cProtection of Animals Used in Experimental and Other Scientific Purposes\u201d (2010\/63\/UE). Authorized project No. PI-03-19.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"34"}}