{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:24Z","timestamp":1787028444875,"version":"build-2736575974"},"reference-count":113,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre and Mossakowski Medical Research Institute, Polish Academy of Sciences, MMRI PAS","award":["Grant2017\/25\/B\/NZ4\/01969 for A.A., Grant FBW-012 for M.G-D."],"award-info":[{"award-number":["Grant2017\/25\/B\/NZ4\/01969 for A.A., Grant FBW-012 for M.G-D."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficient social interaction and communication besides repetitive, stereotyped behaviours. A characteristic feature of ASD is altered dendritic spine density and morphology associated with synaptic plasticity disturbances. Since microtubules (MTs) regulate dendritic spine morphology and play an important role in spine development and plasticity the aim of the present study was to investigate the alterations in the content of neuronal \u03b1\/\u03b2-tubulin and Tau protein level as well as phosphorylation state in the valproic acid (VPA)-induced rat model of autism. Our results indicated that maternal exposure to VPA induces: (1) decrease the level of \u03b1\/\u03b2-tubulin along with Tau accumulation in the hippocampus and cerebral cortex; (2) excessive Tau phosphorylation and activation of Tau-kinases: CDK5, ERK1\/2, and p70S6K in the cerebral cortex; (3) up-regulation of mTOR kinase-dependent signalling in the hippocampus and cerebral cortex of adolescent rat offspring. Moreover, immunohistochemical staining showed histopathological changes in neurons (chromatolysis) in both analysed brain structures of rats prenatally exposed to VPA. The observed changes in Tau protein together with an excessive decrease in \u03b1\/\u03b2-tubulin level may suggest destabilization and thus dysfunction of the MT cytoskeleton network, which in consequence may lead to the disturbance in synaptic plasticity and the development of autistic-like behaviours.<\/jats:p>","DOI":"10.3390\/ijms22063209","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T11:13:26Z","timestamp":1616411606000},"page":"3209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Alterations in Tau Protein Level and Phosphorylation State in the Brain of the Autistic-Like Rats Induced by Prenatal Exposure to Valproic Acid"],"prefix":"10.3390","volume":"22","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 Institute, Polish Academy of Sciences, Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6933-7643","authenticated-orcid":false,"given":"Agnieszka","family":"Kolasa-Wo\u0142osiuk","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7604-4371","authenticated-orcid":false,"given":"Magdalena","family":"Cie\u015blik","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Institute, 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, \u017bwirki i Wigury 61, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Friedland","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudingerweg 5, 55128 Mainz, Germany"}],"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 Institute, Polish Academy of Sciences, Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s12264-017-0100-y","article-title":"An Overview of Autism Spectrum Disorder, Heterogeneity and Treatment Options","volume":"33","author":"Masi","year":"2017","journal-title":"Neurosci. 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