{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T03:51:24Z","timestamp":1794369084067,"version":"4.9.0"},"reference-count":97,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T00:00:00Z","timestamp":1589760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre (http\/\/www.ncn.gov.pl)","award":["2017\/25\/B\/NZ4\/01969"],"award-info":[{"award-number":["2017\/25\/B\/NZ4\/01969"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental conditions categorized as synaptopathies. Environmental risk factors contribute to ASD aetiology. In particular, prenatal exposure to the anti-epileptic drug valproic acid (VPA) may increase the risk of autism. In the present study, we investigated the effect of prenatal exposure to VPA on the synaptic morphology and expression of key synaptic proteins in the hippocampus and cerebral cortex of young-adult male offspring. To characterize the VPA-induced autism model, behavioural outcomes, microglia-related neuroinflammation, and oxidative stress were analysed. Our data showed that prenatal exposure to VPA impaired communication in neonatal rats, reduced their exploratory activity, and led to anxiety-like and repetitive behaviours in the young-adult animals. VPA-induced pathological alterations in the ultrastructures of synapses accompanied by deregulation of key pre- and postsynaptic structural and functional proteins. Moreover, VPA exposure altered the redox status and expression of proinflammatory genes in a brain region-specific manner. The disruption of synaptic structure and plasticity may be the primary insult responsible for autism-related behaviour in the offspring. The vulnerability of specific synaptic proteins to the epigenetic effects of VPA may highlight the potential mechanisms by which prenatal VPA exposure generates behavioural changes.<\/jats:p>","DOI":"10.3390\/ijms21103576","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T02:48:24Z","timestamp":1589942904000},"page":"3576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Prenatal Exposure to Valproic Acid Affects Microglia and Synaptic Ultrastructure in a Brain-Region-Specific Manner in Young-Adult Male Rats: Relevance to Autism Spectrum Disorders"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9777-1378","authenticated-orcid":false,"given":"Magdalena","family":"G\u0105ssowska-Dobrowolska","sequence":"first","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Cie\u015blik","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz Arkadiusz","family":"Czapski","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henryk","family":"J\u0119\u015bko","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Frontczak-Baniewicz","sequence":"additional","affiliation":[{"name":"Electron Microscopy Platform, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Gewartowska","sequence":"additional","affiliation":[{"name":"Electron Microscopy Platform, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5643-6864","authenticated-orcid":false,"given":"Agnieszka","family":"Dominiak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafa\u0142","family":"Polowy","sequence":"additional","affiliation":[{"name":"Behavior and Metabolism Research Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawi\u0144skiego 5 St, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Kuba","family":"Filipkowski","sequence":"additional","affiliation":[{"name":"Behavior and Metabolism Research Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawi\u0144skiego 5 St, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Babiec","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6867-9377","authenticated-orcid":false,"given":"Agata","family":"Adamczyk","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/cshperspect.a009886","article-title":"Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities","volume":"4","author":"Zoghbi","year":"2012","journal-title":"Cold Spring Harb. 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