{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T17:02:48Z","timestamp":1772211768091,"version":"3.50.1"},"reference-count":109,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010783","name":"Slovensk\u00e1 Akad\u00e9mia Vied","doi-asserted-by":"publisher","award":["VEGA 2\/0124\/19"],"award-info":[{"award-number":["VEGA 2\/0124\/19"]}],"id":[{"id":"10.13039\/100010783","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010783","name":"Slovensk\u00e1 Akad\u00e9mia Vied","doi-asserted-by":"publisher","award":["APVV-19-0435"],"award-info":[{"award-number":["APVV-19-0435"]}],"id":[{"id":"10.13039\/100010783","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Hormonal fluctuations, such as the perinatal period, may increase susceptibility of women to depression, which in turn exert a negative impact on child\u2019s neurodevelopment, becoming a risk factor in development of neuropsychiatric disorders. Moreover, the use of antidepressants during this critical period presents a serious health concern for both the mother and the child, due to the consequences of treatment in terms of the reliability and safety for the proper neurodevelopment of the organism being not well known. Atypical antidepressants, such as mirtazapine, that targets both serotonergic and noradrenergic systems in the central nervous system (CNS), represent a novel focus of research due to its unique pharmacological profile. The aim of this work was to study the effects of maternal depression and\/or perinatal antidepressant mirtazapine treatment on the neurobehavioral development of the offspring. Pre-gestationally chronically stressed or non-stressed Wistar rat dams were treated with either mirtazapine (10 mg\/kg\/day) or vehicle during pregnancy and lactation followed by analysis of offspring\u2019s behavior at juvenile and adolescent age. We found mirtazapine induced significant alterations of nursing behavior. In offspring, pregestational stress (PS) had an anxiogenic effect on adolescent males (p\u22640.05) and increased their active behavior in forced swim test (p\u22640.01). Interaction between pregestational stress and mirtazapine treatment variously induced anxiolytic changes of juvenile (p\u22640.05) and adolescent (p\u22640.05) females and impairment of spatial memory (p\u22640.01) in adolescent females as well. Hippocampal density of synaptophysin, pre-synaptic protein marker, was decreased mainly by mirtazapine treatment. In conclusion, our results show mirtazapine induced significant alterations in maternal behavior and several sex- and age-dependent changes in neurobehavioral development of offspring caused by both prenatal mirtazapine treatment and\/or chronic pregestational stress.<\/jats:p>","DOI":"10.1371\/journal.pone.0255546","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T13:50:27Z","timestamp":1643896227000},"page":"e0255546","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sex- and age- dependent effect of pre-gestational chronic stress and mirtazapine treatment on neurobehavioral development of Wistar rat offspring"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9061-1099","authenticated-orcid":true,"given":"Mireia","family":"Vi\u00f1as-Noguera","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krist\u00edna","family":"Csatl\u00f3sov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"\u0160imon\u010di\u010dov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ezster","family":"B\u00f6gi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard","family":"Ujh\u00e1zy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Dubovick\u00fd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krist\u00edna","family":"Belovi\u010dov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"issue":"10","key":"pone.0255546.ref001","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1007\/s00213-019-05326-9","article-title":"Stress, sex hormones, inflammation, and major depressive disorder: Extending Social Signal Transduction Theory of Depression to account for sex differences in mood disorders","volume":"236","author":"GM Slavich","year":"2019","journal-title":"Psychopharmacology (Berl)"},{"key":"pone.0255546.ref002","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.neuroscience.2015.01.048","article-title":"Effects of stress early in gestation on hippocampal neurogenesis and glucocorticoid receptor density in pregnant rats","volume":"290","author":"JL Pawluski","year":"2015","journal-title":"Neuroscience"},{"issue":"1","key":"pone.0255546.ref003","first-page":"1","article-title":"The BDNF-FoxO1 Axis in the medial prefrontal cortex modulates depressive-like behaviors induced by chronic unpredictable stress in postpartum female mice","volume":"13","author":"J Liu","year":"2020","journal-title":"Mol Brain"},{"issue":"7","key":"pone.0255546.ref004","first-page":"341","article-title":"Physiology of pregnancy. 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