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(miRNAs) play a crucial role in the regulation of gene expression levels and have been implicated in the pathogenesis of autism spectrum disorder (ASD) and schizophrenia (SCZ). In this study, we examined the adult expression profiles of specific miRNAs in the prefrontal cortex (PFC) of a neurodevelopmental mouse model for ASD and SCZ that mimics perinatal pathology, such as NMDA receptor hypofunction, and exhibits behavioral and neurophysiological phenotypes related to these disorders during adulthood. To model the early neuropathogenesis of the disorders, mouse pups were administered subcutaneously with ketamine (30 mg\/Kg) at postnatal days 7, 9, and 11. We focused on a set of miRNAs most frequently altered in ASD (miR-451a and miR-486-3p) and in SCZ (miR-132-3p and miR-137-3p) according to human studies. Additionally, we explored miRNAs whose alterations have been identified in both disorders (miR-21-5p, miR-92a-2-5p, miR-144-3p, and miR-146a-5p). We placed particular emphasis on studying the sexual dimorphism in the dynamics of these miRNAs. Our findings revealed significant alterations in the PFC of this ASD- and SCZ-like mouse model. Specifically, we observed upregulated miR-451a and downregulated miR-137-3p. Furthermore, we identified sexual dimorphism in the expression of miR-132-3p, miR-137-3p, and miR-92a-2-5p. From a translational perspective, our results emphasize the potential involvement of miR-92a-2-5p, miR-132-3p, miR-137-3p, and miR-451a in the pathophysiology of ASD and SCZ and strengthen their potential as biomarkers and therapeutic targets of such disorders.<\/jats:p>","DOI":"10.3390\/ijms25052786","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T03:37:57Z","timestamp":1709091477000},"page":"2786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exploratory Analysis of MicroRNA Alterations in a Neurodevelopmental Mouse Model for Autism Spectrum Disorder and Schizophrenia"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6091-2824","authenticated-orcid":false,"given":"Susana","family":"Garc\u00eda-Cerro","sequence":"first","affiliation":[{"name":"Translational Psychiatry Group, Ibis-Biomedicine Institute of Sevilla-CSIC, Manuel Siurot AV, 41013 Seville, Spain"},{"name":"Spanish Network for Research in Mental Health (CIBERSAM), Monforte de Lemos AV, 3-5, 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4794-8249","authenticated-orcid":false,"given":"Ana","family":"G\u00f3mez-Garrido","sequence":"additional","affiliation":[{"name":"Translational Psychiatry Group, Ibis-Biomedicine Institute of Sevilla-CSIC, Manuel Siurot AV, 41013 Seville, Spain"},{"name":"Spanish Network for Research in Mental Health (CIBERSAM), Monforte de Lemos AV, 3-5, 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-5362","authenticated-orcid":false,"given":"Gon\u00e7alo","family":"Garcia","sequence":"additional","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Lab, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"given":"Benedicto","family":"Crespo-Facorro","sequence":"additional","affiliation":[{"name":"Translational Psychiatry Group, Ibis-Biomedicine Institute of Sevilla-CSIC, Manuel Siurot AV, 41013 Seville, Spain"},{"name":"Spanish Network for Research in Mental Health (CIBERSAM), Monforte de Lemos AV, 3-5, 28029 Madrid, Spain"},{"name":"Mental Health Unit, Virgen del Rocio University Hospital, Manuel Siurot AV, 41013 Seville, Spain"},{"name":"Department of Psychiatry, Faculty of Medicine, University of Seville, S\u00e1nchez Pizju\u00e1n AV, 41013 Seville, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3024-9777","authenticated-orcid":false,"given":"Dora","family":"Brites","sequence":"additional","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Lab, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1242\/dev.144337","article-title":"MicroRNAs in Neural Development: From Master Regulators to Fine-Tuners","volume":"144","author":"Rajman","year":"2017","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.expneurol.2014.08.005","article-title":"MicroRNAs: Small Molecules with Big Roles in Neurodevelopment and Diseases","volume":"268","author":"Sun","year":"2015","journal-title":"Exp. 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