{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T05:20:54Z","timestamp":1772342454100,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971285"],"award-info":[{"award-number":["81971285"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2020JM-305"],"award-info":[{"award-number":["2020JM-305"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["GK202005001"],"award-info":[{"award-number":["GK202005001"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["GK202105001"],"award-info":[{"award-number":["GK202105001"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["GK202103155"],"award-info":[{"award-number":["GK202103155"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Autism spectrum disorders (ASD) represent a group of neurodevelopmental defects characterized by social deficits and repetitive behaviors. Alteration in Glycosylation patterns could influence the nervous system development and contribute to the molecular mechanism of ASD. Interaction of environmental factors with susceptible genes may affect expressions of glycosylation-related genes and thus result in abnormal glycosylation patterns. Here, we used an environmental factor-induced model of autism by a single intraperitoneal injection of 400 mg\/kg valproic acid (VPA) to female rats at day 12.5 post-conception. Following confirmation of reduced sociability and increased self-grooming behaviors in VPA-treated offspring, we analyzed the alterations in the expression profile of glycan patterns and glycan-related genes by lectin microarrays and RNA-seq, respectively. Lectin microarrays detected 14 significantly regulated lectins in VPA rats, with an up-regulation of high-mannose with antennary and down-regulation of Sia\u03b12-3 Gal\/GalNAc. Based on the KEGG and CAZy resources, we assembled a comprehensive list of 961 glycan-related genes to focus our analysis on specific genes. Of those, transcription results revealed that there were 107 differentially expressed glycan-related genes (DEGGs) after VPA treatment. Functional analysis of DEGGs encoding anabolic enzymes revealed that the process trimming to form core structure and glycan extension from core structure primarily changed, which is consistent with the changes in glycan patterns. In addition, the DEGGs encoding glycoconjugates were mainly related to extracellular matrix and axon guidance. This study provides insights into the underlying molecular mechanism of aberrant glycosylation after prenatal VPA exposure, which may serve as potential biomarkers for the autism diagnosis.<\/jats:p>","DOI":"10.3389\/fncel.2022.1057857","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T07:12:15Z","timestamp":1670483535000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Altered expression of glycan patterns and glycan-related genes in the medial prefrontal cortex of the valproic acid rat model of autism"],"prefix":"10.3389","volume":"16","author":[{"given":"Yingxun","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Di","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoqiang","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoming","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingfang","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","year":"2013","journal-title":"Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"B2","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1093\/cercor\/bhw349","article-title":"The Number of Chandelier and Basket Cells Are Differentially Decreased in Prefrontal Cortex in Autism.","volume":"28","author":"Ariza","year":"2018","journal-title":"Cereb. Cortex"},{"key":"B3","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.neubiorev.2011.06.008","article-title":"BTBR T+tf\/J mice: Autism-relevant behaviors and reduced fractone-associated heparan sulfate.","volume":"36","author":"Blanchard","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B4","doi-asserted-by":"publisher","first-page":"104266","DOI":"10.1016\/j.jprot.2021.104266","article-title":"Integrating transcriptomics, proteomics, glycomics and glycoproteomics to characterize paclitaxel resistance in breast cancer cells.","volume":"243","author":"Cao","year":"2021","journal-title":"J. Proteomics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1159\/000375489","article-title":"Differential Local Connectivity and Neuroinflammation Profiles in the Medial Prefrontal Cortex and Hippocampus in the Valproic Acid Rat Model of Autism.","volume":"37","author":"Codagnone","year":"2015","journal-title":"Dev. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"415","DOI":"10.9758\/cpn.2019.17.3.415","article-title":"Levels of Salivary Sialic Acid in Children with Autism Spectrum Disorder; Could It Be Related to Stereotypes and Hyperactivity?","volume":"17","author":"Demirci","year":"2019","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4544","DOI":"10.1039\/D0FO02926B","article-title":"Maternal folic acid supplementation prevents autistic behaviors in a rat model induced by prenatal exposure to valproic acid.","volume":"12","author":"Di","year":"2021","journal-title":"Food Funct"},{"key":"B8","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.mam.2016.07.001","article-title":"Glycan susceptibility factors in autism spectrum disorders.","volume":"51","author":"Dwyer","year":"2016","journal-title":"Mol. Aspects Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1146\/annurev-neuro-071714-034019","article-title":"Neurological aspects of human glycosylation disorders.","volume":"38","author":"Freeze","year":"2015","journal-title":"Annu. Rev. Neurosci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.neures.2009.05.002","article-title":"Valproic acid induces up- or down-regulation of gene expression responsible for the neuronal excitation and inhibition in rat cortical neurons through its epigenetic actions.","volume":"65","author":"Fukuchi","year":"2009","journal-title":"Neurosci. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1007\/s12035-020-01878-6","article-title":"Differential expression of hippocampal circular rnas in the btbr mouse model for autism spectrum disorder.","volume":"57","author":"Gasparini","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/nature12605","article-title":"LARGE glycans on dystroglycan function as a tunable matrix scaffold to prevent dystrophy.","volume":"503","author":"Goddeeris","year":"2013","journal-title":"Nature"},{"key":"B13","doi-asserted-by":"publisher","first-page":"5052","DOI":"10.1073\/pnas.1117881109","article-title":"Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate.","volume":"109","author":"Irie","year":"2012","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: New perspectives on genomes, pathways, diseases and drugs.","volume":"45","author":"Kanehisa","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"422","DOI":"10.3389\/fncel.2018.00422","article-title":"Molecular pathology and pharmacological treatment of autism spectrum disorder-like phenotypes using rodent models.","volume":"12","author":"Kuo","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1002\/aur.1338","article-title":"Altered peripheral and central inflammatory responses in a mouse model of autism.","volume":"7","author":"Lucchina","year":"2014","journal-title":"Autism Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"W501","DOI":"10.1093\/nar\/gkx372","article-title":"Pathview web: User friendly pathway visualization and data integration.","volume":"45","author":"Luo","year":"2017","journal-title":"Nucleic Acids Research"},{"key":"B18","doi-asserted-by":"publisher","first-page":"285","DOI":"10.5607\/en.2015.24.4.285","article-title":"Exploring the validity of valproic acid animal model of autism.","volume":"24","author":"Mabunga","year":"2015","journal-title":"Exp. Neurobiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.neuroscience.2018.11.016","article-title":"Auditory midbrain hypoplasia and dysmorphology after prenatal valproic acid exposure.","volume":"396","author":"Mansour","year":"2019","journal-title":"Neuroscience"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e13002","DOI":"10.1371\/journal.pone.0013002","article-title":"Glycogene expression alterations associated with pancreatic cancer epithelial-mesenchymal transition in complementary model systems.","volume":"5","author":"Maupin","year":"2010","journal-title":"PLoS One"},{"key":"B21","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1001\/jamapsychiatry.2017.4685","article-title":"The emerging clinical neuroscience of autism spectrum disorder: A review.","volume":"75","author":"Muhle","year":"2018","journal-title":"JAMA Psychiatry"},{"key":"B22","doi-asserted-by":"publisher","first-page":"5143","DOI":"10.3390\/ijms22105143","article-title":"Glycosylation in axonal guidance.","volume":"22","author":"Mutalik","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"17298","DOI":"10.1074\/jbc.M801964200","article-title":"Regulation of glycan structures in animal tissues: Transcript profiling of glycan-related genes.","volume":"283","author":"Nairn","year":"2008","journal-title":"Journal of Biological Chemistry"},{"key":"B24","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1093\/glycob\/cwz045","article-title":"Updates to the symbol nomenclature for glycans guidelines.","volume":"29","author":"Neelamegham","year":"2019","journal-title":"Glycobiology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e13190","DOI":"10.1111\/acel.13190","article-title":"Glycome profiling by lectin microarray reveals dynamic glycan alterations during epidermal stem cell aging.","volume":"19","author":"Oinam","year":"2020","journal-title":"Aging Cell"},{"key":"B26","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.pnpbp.2017.04.009","article-title":"Altered expression of circadian rhythm and extracellular matrix genes in the medial prefrontal cortex of a valproic acid rat model of autism.","volume":"77","author":"Olde Loohuis","year":"2017","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B27","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.bbr.2012.12.062","article-title":"Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles.","volume":"243","author":"Pearson","year":"2013","journal-title":"Behav. Brain Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"46041","DOI":"10.1038\/srep46041","article-title":"Serum glycopattern and Maackia amurensis lectin-II binding glycoproteins in autism spectrum disorder.","volume":"7","author":"Qin","year":"2017","journal-title":"Sci. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41576-018-0066-2","article-title":"Autism spectrum disorder: Insights into convergent mechanisms from transcriptomics.","volume":"20","author":"Quesnel-Vallieres","year":"2019","journal-title":"Nat Rev Genet"},{"key":"B30","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3389\/neuro.04.004.2008","article-title":"Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic Acid animal model of autism.","volume":"2","author":"Rinaldi","year":"2008","journal-title":"Front. Neural Circ."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1744806918783931","DOI":"10.1177\/1744806918783931","article-title":"Plastic change of prefrontal cortex mediates anxiety-like behaviors associated with chronic pain in neuropathic rats.","volume":"14","author":"Sang","year":"2018","journal-title":"Mol. Pain"},{"key":"B32","doi-asserted-by":"publisher","first-page":"4075","DOI":"10.3390\/ijms23084075","article-title":"Resveratrol prevents cytoarchitectural and interneuronal alterations in the valproic acid rat model of autism.","volume":"23","author":"Santos-Terra","year":"2022","journal-title":"Int. J. Mol. Sci"},{"key":"B33","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1038\/s41580-020-00294-x","article-title":"Global view of human protein glycosylation pathways and functions.","volume":"21","author":"Schjoldager","year":"2020","journal-title":"Nat. Rev Mol. Cell Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"107477","DOI":"10.1016\/j.neuropharm.2018.12.024","article-title":"Prenatal valproate in rodents as a tool to understand the neural underpinnings of social dysfunctions in autism spectrum disorder.","volume":"159","author":"Tartaglione","year":"2019","journal-title":"Neuropharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e5324","DOI":"10.1371\/journal.pone.0005324","article-title":"Gene-network analysis identifies susceptibility genes related to glycobiology in autism.","volume":"4","author":"van der Zwaag","year":"2009","journal-title":"PLoS One"},{"key":"B36","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1007\/s00401-017-1736-4","article-title":"Autism spectrum disorder: Neuropathology and animal models.","volume":"134","author":"Varghese","year":"2017","journal-title":"Acta Neuropathologica"},{"key":"B37","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jprot.2016.05.013","article-title":"Maternal alterations in the proteome of the medial prefrontal cortex in rat.","volume":"153","author":"V\u00f6lgyi","year":"2017","journal-title":"J. Proteomics"},{"key":"B38","doi-asserted-by":"publisher","first-page":"112836","DOI":"10.1016\/j.bbr.2020.112836","article-title":"Abnormal reinforcement learning in a mice model of autism induced by prenatal exposure to valproic acid.","volume":"395","author":"Wu","year":"2020","journal-title":"Behav. Brain Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e21013","DOI":"10.1097\/MD.0000000000021013","article-title":"The level of GNE and its relationship with behavioral phenotypes in children with autism spectrum disorder.","volume":"99","author":"Yang","year":"2020","journal-title":"Medicine"},{"key":"B40","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.brainres.2017.10.027","article-title":"Sialic acid and anti-ganglioside antibody levels in children with autism spectrum disorders.","volume":"1678","author":"Yang","year":"2018","journal-title":"Brain Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"5277","DOI":"10.1021\/pr300484j","article-title":"Analysis of glycan-related genes expression and glycan profiles in mice with liver fibrosis.","volume":"11","author":"Yu","year":"2012","journal-title":"J. Proteome Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.reprotox.2018.01.008","article-title":"Transcriptional and splicing dysregulation in the prefrontal cortex in valproic acid rat model of autism.","volume":"77","author":"Zhang","year":"2018","journal-title":"Reprod. Toxicol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1007\/s11033-016-4015-x","article-title":"Validation of reference genes for quantitative real-time PCR in valproic acid rat models of autism.","volume":"43","author":"Zhou","year":"2016","journal-title":"Mol. Biol. Rep."}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2022.1057857\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T07:12:18Z","timestamp":1670483538000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2022.1057857\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":43,"alternative-id":["10.3389\/fncel.2022.1057857"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2022.1057857","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,8]]},"article-number":"1057857"}}