{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T08:48:46Z","timestamp":1791535726775,"version":"4.3.4"},"reference-count":84,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T00:00:00Z","timestamp":1649289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institutos Nacionais de Ci\u00eancia e Tecnologia","award":["465489\/2014-1"],"award-info":[{"award-number":["465489\/2014-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by several alterations, including disorganized brain cytoarchitecture and excitatory\/inhibitory (E\/I) imbalance. We aimed to analyze aspects associated with the inhibitory components in ASD, using bioinformatics to develop notions about embryonic life and tissue analysis for postnatal life. We analyzed microarray and RNAseq datasets of embryos from different ASD models, demonstrating that regions involved in neuronal development are affected. We evaluated the effect of prenatal treatment with resveratrol (RSV) on the neuronal organization and quantity of parvalbumin-positive (PV+), somatostatin-positive (SOM+), and calbindin-positive (CB+) GABAergic interneurons, besides the levels of synaptic proteins and GABA receptors in the medial prefrontal cortex (mPFC) and hippocampus (HC) of the ASD model induced by valproic acid (VPA). VPA increased the total number of neurons in the mPFC, while it reduced the number of SOM+ neurons, as well as the proportion of SOM+, PV+, and CB+ neurons (subregion-specific manner), with preventive effects of RSV. In summary, metabolic alterations or gene expression impairments could be induced by VPA, leading to extensive damage in the late developmental stages. By contrast, due to its antioxidant, neuroprotective, and opposite action on histone properties, RSV may avoid damages induced by VPA.<\/jats:p>","DOI":"10.3390\/ijms23084075","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T13:39:51Z","timestamp":1649338791000},"page":"4075","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Resveratrol Prevents Cytoarchitectural and Interneuronal Alterations in the Valproic Acid Rat Model of Autism"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8079-452X","authenticated-orcid":false,"given":"J\u00falio","family":"Santos-Terra","sequence":"first","affiliation":[{"name":"Translational Research Group in Autism Spectrum Disorder\u2014GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"National Institute of Science and Technology in Neuroimmunomodulation\u2014INCT-NIM, Rio de Janeiro 21040-900, Brazil"},{"name":"Autism Wellbeing and Research Development\u2014AWARD\u2014Initiative BR-UK-CA, Porto Alegre 90040-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6423-1938","authenticated-orcid":false,"given":"Iohanna","family":"Deckmann","sequence":"additional","affiliation":[{"name":"Translational Research Group in Autism Spectrum Disorder\u2014GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"National Institute of Science and Technology in Neuroimmunomodulation\u2014INCT-NIM, Rio de Janeiro 21040-900, Brazil"},{"name":"Autism Wellbeing and Research Development\u2014AWARD\u2014Initiative BR-UK-CA, Porto Alegre 90040-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Carello-Collar","sequence":"additional","affiliation":[{"name":"Translational Research Group in Autism Spectrum Disorder\u2014GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"National Institute of Science and Technology in Neuroimmunomodulation\u2014INCT-NIM, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9323-3556","authenticated-orcid":false,"given":"Gustavo Della-Flora","family":"Nunes","sequence":"additional","affiliation":[{"name":"Translational Research Group in Autism Spectrum Disorder\u2014GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"National Institute of Science and Technology in Neuroimmunomodulation\u2014INCT-NIM, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0956-557X","authenticated-orcid":false,"given":"Guilherme","family":"Bauer-Negrini","sequence":"additional","affiliation":[{"name":"Translational Research Group in Autism Spectrum Disorder\u2014GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"National Institute of Science and Technology in Neuroimmunomodulation\u2014INCT-NIM, Rio de Janeiro 21040-900, Brazil"},{"name":"Autism Wellbeing and Research Development\u2014AWARD\u2014Initiative BR-UK-CA, Porto Alegre 90040-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Brum","family":"Schwingel","sequence":"additional","affiliation":[{"name":"Translational Research Group in Autism Spectrum Disorder\u2014GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"National Institute of Science and Technology in Neuroimmunomodulation\u2014INCT-NIM, Rio de Janeiro 21040-900, Brazil"},{"name":"Autism Wellbeing and Research Development\u2014AWARD\u2014Initiative BR-UK-CA, Porto Alegre 90040-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mellanie","family":"Fontes-Dutra","sequence":"additional","affiliation":[{"name":"Translational Research Group in Autism Spectrum Disorder\u2014GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"National Institute of Science and Technology in Neuroimmunomodulation\u2014INCT-NIM, Rio de Janeiro 21040-900, Brazil"},{"name":"Autism Wellbeing and Research Development\u2014AWARD\u2014Initiative BR-UK-CA, Porto Alegre 90040-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudimar","family":"Riesgo","sequence":"additional","affiliation":[{"name":"Translational Research Group in Autism Spectrum Disorder\u2014GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"National Institute of Science and Technology in Neuroimmunomodulation\u2014INCT-NIM, Rio de Janeiro 21040-900, Brazil"},{"name":"Autism Wellbeing and Research Development\u2014AWARD\u2014Initiative BR-UK-CA, Porto Alegre 90040-060, Brazil"},{"name":"Child Neurology Unit, Department of Pediatrics, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre 90035-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8838-1300","authenticated-orcid":false,"given":"Carmem","family":"Gottfried","sequence":"additional","affiliation":[{"name":"Translational Research Group in Autism Spectrum Disorder\u2014GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil"},{"name":"National Institute of Science and Technology in Neuroimmunomodulation\u2014INCT-NIM, Rio de Janeiro 21040-900, Brazil"},{"name":"Autism Wellbeing and Research Development\u2014AWARD\u2014Initiative BR-UK-CA, Porto Alegre 90040-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (DSM-5), American Psychiatric Association. American Psychiatric DSM 5.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.ss6904a1","article-title":"Prevalence of autism spectrum disorder among children aged 8 Years-Autism and developmental disabilities monitoring network, 11 Sites, United States, 2016","volume":"69","author":"Maenner","year":"2020","journal-title":"MMWR Surveill. Summ."},{"key":"ref_3","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. Bull."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"k1674","DOI":"10.1136\/bmj.k1674","article-title":"Autism spectrum disorder: Advances in diagnosis and evaluation","volume":"361","author":"Zwaigenbaum","year":"2018","journal-title":"BMJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.chc.2020.01.001","article-title":"Diagnosis of Autism Spectrum Disorder Across the Lifespan","volume":"29","author":"Shulman","year":"2020","journal-title":"Child Adolesc. Psychiatr. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1017\/S003329171400172X","article-title":"The epidemiology and global burden of autism spectrum disorders","volume":"45","author":"Baxter","year":"2015","journal-title":"Psychol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1203\/PDR.0b013e31819e7168","article-title":"The Role of Epilepsy and Epileptiform EEGs in Autism Spectrum Disorders","volume":"65","author":"Spence","year":"2009","journal-title":"Pediatr. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1192\/bjp.bp.109.076877","article-title":"Epilepsy in autism: Features and correlates","volume":"198","author":"Bolton","year":"2011","journal-title":"Br. J. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.yebeh.2019.07.037","article-title":"The co-occurrence of epilepsy and autism: A systematic review","volume":"98","author":"Lukmanji","year":"2019","journal-title":"Epilepsy Behav."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.neuron.2015.07.033","article-title":"Excitatory\/Inhibitory Balance and Circuit Homeostasis in Autism Spectrum Disorders","volume":"87","author":"Nelson","year":"2015","journal-title":"Neuron"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/ejn.13595","article-title":"Neurobiological bases of autism-epilepsy comorbidity: A focus on excitation\/inhibition imbalance","volume":"47","author":"Bozzi","year":"2018","journal-title":"Eur. J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.12688\/f1000research.12155.1","article-title":"Inhibitory control of the excitatory\/inhibitory balance in psychiatric disorders","volume":"7","author":"Selten","year":"2018","journal-title":"F1000Research"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuropharm.2014.09.011","article-title":"Tasks for inhibitory interneurons in intact brain circuits","volume":"88","author":"Roux","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1152\/physrev.00007.2017","article-title":"Hippocampal GABAergic Inhibitory Interneurons","volume":"97","author":"Pelkey","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/nrn1519","article-title":"Interneurons of the neocortical inhibitory system","volume":"5","author":"Markram","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.neuron.2016.06.033","article-title":"GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits","volume":"91","author":"Tremblay","year":"2016","journal-title":"Neuron"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nrn3444","article-title":"New insights into the classification and nomenclature of cortical GABAergic interneurons","volume":"14","author":"Defelipe","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/2045-3701-3-19","article-title":"Development and specification of GABAergic cortical interneurons","volume":"3","author":"Kelsom","year":"2013","journal-title":"Cell Biosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nn.3051","article-title":"Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex","volume":"15","author":"Gentet","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e27868","DOI":"10.7554\/eLife.27868","article-title":"Parvalbumin-positive interneurons mediate neocortical-hippocampal interactions that are necessary for memory consolidation","volume":"6","author":"Xia","year":"2017","journal-title":"eLife"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1038\/s41593-020-0647-1","article-title":"Cross-hemispheric gamma synchrony between prefrontal parvalbumin interneurons supports behavioral adaptation during rule shift learning","volume":"23","author":"Cho","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1152\/jn.90752.2008","article-title":"Imbalance of Neocortical Excitation and Inhibition and Altered UP States Reflect Network Hyperexcitability in the Mouse Model of Fragile X Syndrome","volume":"100","author":"Gibson","year":"2008","journal-title":"J. Neurophysiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nn.4471","article-title":"Modulation of excitation on parvalbumin interneurons by neuroligin-3 regulates the hippocampal network","volume":"20","author":"Polepalli","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5036","DOI":"10.1038\/ncomms6036","article-title":"Conditional deletion of Mecp2 in parvalbumin-expressing GABAergic cells results in the absence of critical period plasticity","volume":"5","author":"He","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/nn1754","article-title":"Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy","volume":"9","author":"Yu","year":"2006","journal-title":"Nat. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s10803-008-0646-7","article-title":"GABAAreceptor downregulation in brains of subjects with autism","volume":"39","author":"Fatemi","year":"2009","journal-title":"J. Autism Dev. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.neuron.2014.07.040","article-title":"Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits","volume":"83","author":"Tang","year":"2014","journal-title":"Neuron"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/ajmg.a.37977","article-title":"Neuroligin 2 nonsense variant associated with anxiety, autism, intellectual disability, hyperphagia, and obesity","volume":"173","author":"Parente","year":"2017","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3389\/fncel.2018.00470","article-title":"Synaptopathology involved in autism spectrum disorder","volume":"12","author":"Guang","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.bbi.2018.05.005","article-title":"Maternal immune activation with staphylococcal enterotoxin A produces unique behavioral changes in C57BL\/6 mouse offspring","volume":"75","author":"Glass","year":"2019","journal-title":"Brain. Behav. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3389\/fnbeh.2018.00230","article-title":"Increasing role of maternal immune activation in neurodevelopmental disorders","volume":"12","author":"Pancaro","year":"2018","journal-title":"Front. Behav. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.bbi.2012.01.015","article-title":"Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response","volume":"26","author":"Oskvig","year":"2012","journal-title":"Brain. Behav. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2018.12.002","article-title":"Brain changes in a maternal immune activation model of neurodevelopmental brain disorders","volume":"175","author":"Bergdolt","year":"2019","journal-title":"Prog. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fontes-Dutra, M., Rabelo, B., Santos-Terra, J., Deckmann, I., Schwingel, G.B., and Gottfried, C. (2020). Maternal Immune Activation and Neuropsychiatric Disorders: The Intricate Puzzle of Autism Spectrum Disorder. Perinatal Inflammation and Adult Psychopathology, Springer.","DOI":"10.1007\/978-3-030-39335-9_11"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.neulet.2014.09.039","article-title":"Resveratrol prevents social deficts in animal model of autism induced by valproic acid","volume":"583","author":"Zanatta","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fnsyn.2018.00009","article-title":"Resveratrol prevents cellular and behavioral sensory alterations in the animal model of autism induced by valproic acid","volume":"10","author":"Deckmann","year":"2018","journal-title":"Front. Synaptic Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.bbr.2019.01.034","article-title":"Abnormal empathy-like pro-social behaviour in the valproic acid model of autism spectrum disorder","volume":"364","author":"Hirsch","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.fct.2018.02.061","article-title":"Behavioral alterations in autism model induced by valproic acid and translational analysis of circulating microRNA","volume":"115","author":"Hirsch","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Gottfried, C., Bambini-Junior, V., Baronio, D., Zanatta, G., Bristot, R., Vaccaro, T., and Riesgo, R. (2013). Valproic Acid in Autism Spectrum Disorder: From an Environmental Risk Factor to a Reliable Animal Model. Recent Advances in Autism Spectrum Disorders, IntechOpen.","DOI":"10.5772\/54824"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s12640-016-9660-2","article-title":"Maternal Exposure to Valproic Acid Primarily Targets Interneurons Followed by Late Effects on Neurogenesis in the Hippocampal Dentate Gyrus in Rat Offspring","volume":"31","author":"Watanabe","year":"2017","journal-title":"Neurotox. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"147593","DOI":"10.1016\/j.brainres.2021.147593","article-title":"Resveratrol prevents long-term structural hippocampal alterations and modulates interneuron organization in an animal model of ASD","volume":"1768","author":"Deckmann","year":"2021","journal-title":"Brain Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1159\/000492113","article-title":"Neuroimmune Alterations in Autism: A Translational Analysis Focusing on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid","volume":"25","author":"Deckmann","year":"2018","journal-title":"Neuroimmunomodulation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1159\/000491395","article-title":"Reduced CD4 T Lymphocytes in Lymph Nodes of the Mouse Model of Autism Induced by Valproic Acid","volume":"25","author":"Baronio","year":"2018","journal-title":"Neuroimmunomodulation"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Cristiano, C., Volpicelli, F., Crispino, M., Lacivita, E., Russo, R., Leopoldo, M., Calignano, A., and Perrone-Capano, C. (2022). Behavioral, Anti-Inflammatory, and Neuroprotective Effects of a Novel FPR2 Agonist in Two Mouse Models of Autism. Pharmaceuticals, 15.","DOI":"10.3390\/ph15020161"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s11011-016-9927-6","article-title":"Neurobehavioural evaluation of resveratrol in murine models of anxiety and schizophrenia","volume":"32","author":"Magaji","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref_46","first-page":"799","article-title":"Resveratrol adjunct to methylphenidate improves symptoms of attention-deficit\/hyperactivity disorder: A randomized, double-blinded, placebo-controlled clinical trial","volume":"30","author":"Moradi","year":"2020","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.1749-6632.2010.05857.x","article-title":"Resveratrol modulates astroglial functions: Neuroprotective hypothesis","volume":"1215","author":"Gottfried","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"108013","DOI":"10.1016\/j.pharmthera.2021.108013","article-title":"Polyphenols and neuroprotection: Therapeutic implications for cognitive decline","volume":"232","author":"Caruso","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00401-006-0085-5","article-title":"Minicolumnar abnormalities in autism","volume":"112","author":"Casanova","year":"2006","journal-title":"Acta Neuropathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1056\/NEJMoa1307491","article-title":"Patches of Disorganization in the Neocortex of Children with Autism","volume":"370","author":"Stoner","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9228","DOI":"10.1523\/JNEUROSCI.3340-04.2004","article-title":"Autism and abnormal development of brain connectivity","volume":"24","author":"Belmonte","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e13374","DOI":"10.7554\/eLife.13374","article-title":"Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation","volume":"5","author":"Zheng","year":"2016","journal-title":"eLife"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11785","DOI":"10.1038\/s41598-020-68725-5","article-title":"Valproate inhibits mitochondrial bioenergetics and increases glycolysis in Saccharomyces cerevisiae","volume":"10","author":"Salsaa","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1124\/mol.111.072314","article-title":"Valproic Acid Increases Formation of Reactive Oxygen Species and Induces Apoptosis in Postimplantation Embryos: A Role for Oxidative Stress in Valproic Acid-Induced Neural Tube Defects","volume":"80","author":"Tung","year":"2011","journal-title":"Mol. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6969","DOI":"10.1093\/emboj\/20.24.6969","article-title":"Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells","volume":"20","author":"Minucci","year":"2001","journal-title":"EMBO J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"36734","DOI":"10.1074\/jbc.M101287200","article-title":"Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen","volume":"276","author":"Phiel","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"17187","DOI":"10.1074\/jbc.M501250200","article-title":"Mechanism of human SIRT1 activation by resveratrol","volume":"280","author":"Borra","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1001\/jama.2011.1638","article-title":"Neuron Number and Size in Prefrontal Cortex of Children With Autism","volume":"306","author":"Courchesne","year":"2011","journal-title":"JAMA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1093\/cercor\/bhy339","article-title":"Objective Morphological Classification of Neocortical Pyramidal Cells","volume":"29","author":"Kanari","year":"2019","journal-title":"Cereb. Cortex"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Wu, Y.K., Fujishima, K., and Kengaku, M. (2015). Differentiation of Apical and Basal Dendrites in Pyramidal Cells and Granule Cells in Dissociated Hippocampal Cultures. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118482"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"10908","DOI":"10.1523\/JNEUROSCI.0229-16.2016","article-title":"In Utero Exposure to Valproic Acid Induces Neocortical Dysgenesis via Dysregulation of Neural Progenitor Cell Proliferation\/Differentiation","volume":"36","author":"Fujimura","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.neuron.2005.09.034","article-title":"The temporal and spatial origins of cortical interneurons predict their physiological subtype","volume":"48","author":"Butt","year":"2005","journal-title":"Neuron"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.ijdevneu.2013.01.006","article-title":"The effects of prenatal exposure to valproic acid on the initial development of serotonergic neurons","volume":"31","author":"Oyabu","year":"2013","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"150","DOI":"10.3389\/fnmol.2016.00150","article-title":"Prenatal Valproate Exposure Differentially Affects Parvalbumin-Expressing Neurons and Related Circuits in the Cortex and Striatum of Mice","volume":"9","author":"Lauber","year":"2016","journal-title":"Front. Mol. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/aur.88","article-title":"Decreased GABA A receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism","volume":"2","author":"Oblak","year":"2009","journal-title":"Autism Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.neuron.2009.01.034","article-title":"KCC2 Expression Promotes the Termination of Cortical Interneuron Migration in a Voltage-Sensitive Calcium-Dependent Manner","volume":"62","author":"Bortone","year":"2009","journal-title":"Neuron"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.gde.2012.04.003","article-title":"Notch signaling and neural connectivity","volume":"22","author":"Giniger","year":"2012","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1111\/j.1471-4159.2006.03783.x","article-title":"Notch and NGF\/p75NTR control dendrite morphology and the balance of excitatory\/inhibitory synaptic input to hippocampal neurones through Neurogenin 3","volume":"97","author":"Arevalo","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_69","first-page":"2933","article-title":"Intermittent activation of notch signaling promotes bone formation","volume":"9","author":"Ji","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.neuron.2018.09.029","article-title":"Somatostatin Interneurons Facilitate Hippocampal-Prefrontal Synchrony and Prefrontal Spatial Encoding","volume":"100","author":"Abbas","year":"2018","journal-title":"Neuron"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.stemcr.2015.10.012","article-title":"Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid","volume":"5","author":"Juliandi","year":"2015","journal-title":"Stem Cell Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1177\/1535759719835366","article-title":"Valproic Acid Leads New Neurons Down the Wrong Path","volume":"19","author":"Danzer","year":"2019","journal-title":"Epilepsy Curr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"17807","DOI":"10.1038\/srep17807","article-title":"Resveratrol Treatment after Status Epilepticus Restrains Neurodegeneration and Abnormal Neurogenesis with Suppression of Oxidative Stress and Inflammation","volume":"5","author":"Mishra","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_74","unstructured":"Paxinos, G., and Watson, C. (2004). The Rat Brain in Stereotaxic Coordinates\u2014The New Coronal Set, Academic Press. [5th ed.]."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1002\/jdn.10137","article-title":"Resveratrol prevents brain edema, blood\u2013brain barrier permeability, and altered aquaporin profile in autism animal model","volume":"81","author":"Deckmann","year":"2021","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1007\/s00204-014-1279-6","article-title":"From transient transcriptome responses to disturbed neurodevelopment: Role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects","volume":"88","author":"Balmer","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41378-020-0165-z","article-title":"Neurodevelopmental impairment induced by prenatal valproic acid exposure shown with the human cortical organoid-on-a-chip model","volume":"6","author":"Cui","year":"2020","journal-title":"Microsyst. Nanoeng."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41593-020-00762-9","article-title":"Maternal immune activation in mice disrupts proteostasis in the fetal brain","volume":"24","author":"Kalish","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e60100","DOI":"10.7554\/eLife.60100","article-title":"Sequential perturbations to mouse corticogenesis following in utero maternal immune activation","volume":"10","author":"Canales","year":"2021","journal-title":"eLife"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3448","DOI":"10.1093\/bioinformatics\/bti551","article-title":"BiNGO: A Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks","volume":"21","author":"Maere","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1242\/dmm.005439","article-title":"SFARI Gene: An evolving database for the autism research community","volume":"3","author":"Packer","year":"2010","journal-title":"Dis. Model. Mech."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/8\/4075\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:49:39Z","timestamp":1760136579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/8\/4075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,7]]},"references-count":84,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijms23084075"],"URL":"https:\/\/doi.org\/10.3390\/ijms23084075","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,7]]}}}