{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:55:48Z","timestamp":1790258148858,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition currently diagnosed through subjective behavioral assessments. Objective blood-based biomarkers are needed to enable earlier and more accurate identification. In this study, we aimed to identify synapse-related biomarkers associated with ASD and evaluate their potential as serum-based indicators. Methods: RNA sequencing was performed on the cerebellum, hippocampus, and cerebral cortex of a valproic acid-induced rat model of ASD to identify differentially expressed genes (DEGs). Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, were conducted to explore associated pathways. Synapse-related hub genes were selected by comparison with the SFARI autism gene database, and the serum expression of candidate proteins was assessed using Western blotting. Results: A total of 692, 813, and 1059 DEGs were identified in the cerebellum, hippocampus, and cortex, respectively. Enrichment analyses highlighted dendrite development, postsynaptic density, and glutamatergic synapse pathways as significantly affected. Six synaptic hub genes were prioritized, among which serum MAP1A expression was significantly elevated in the ASD rats. Conclusions: These findings suggest that serum MAP1A may represent a potential biomarker reflecting synaptic abnormalities in ASD. Further validation in human cohorts and integration into a multi-marker framework are warranted to account for the heterogeneity of ASD.<\/jats:p>","DOI":"10.3390\/brainsci16050478","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T15:01:18Z","timestamp":1777474878000},"page":"478","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum MAP1A as a Potential Biomarker for Autism Spectrum Disorder"],"prefix":"10.3390","volume":"16","author":[{"given":"Jiwon","family":"Jeong","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Toxicology, College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hyeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Toxicology, College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6042-5949","authenticated-orcid":false,"given":"Dongsun","family":"Park","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Toxicology, College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1111\/jnc.15338","article-title":"Cerebrospinal fluid and serum protein markers in autism: A co-twin study","volume":"158","author":"Smedler","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/1742-2094-7-48","article-title":"Neurotensin is increased in serum of young children with autistic disorder","volume":"7","author":"Angelidou","year":"2010","journal-title":"J. Neuroinflamm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1212\/WNL.0000000000207193","article-title":"Blood Biomarkers in Neurodegenerative Diseases: Implications for the Clinical Neurologist","volume":"101","author":"Alcolea","year":"2023","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/ane.13698","article-title":"Blood biomarkers in ALS: Challenges, applications and novel frontiers","volume":"146","author":"Sturmey","year":"2022","journal-title":"Acta Neurol. Scand."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1093\/schbul\/sbae044","article-title":"Shared Genetic Determinants of Schizophrenia and Autism Spectrum Disorder Implicate Opposite Risk Patterns: A Genome-Wide Analysis of Common Variants","volume":"50","author":"Chen","year":"2024","journal-title":"Schizophr. Bull."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neubiorev.2021.07.014","article-title":"The neuropathology of autism: A systematic review of post-mortem studies of autism and related disorders","volume":"129","author":"Fetit","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Satam, H., Joshi, K., Mangrolia, U., Waghoo, S., Zaidi, G., Rawool, S., Thakare, R.P., Banday, S., Mishra, A.K., and Das, G. (2023). Next-Generation Sequencing Technology: Current Trends and Advancements. Biology, 12.","DOI":"10.3390\/biology12070997"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014A Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1007\/s12035-016-9715-7","article-title":"The Functional and Molecular Properties, Physiological Functions, and Pathophysiological Roles of GluN2A in the Central Nervous System","volume":"54","author":"Sun","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.biopsych.2023.04.014","article-title":"The Neurogenetics of Functional Connectivity Alterations in Autism: Insights From Subtyping in 657 Individuals","volume":"94","author":"Rasero","year":"2023","journal-title":"Biol. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e12959","DOI":"10.1111\/cpr.12959","article-title":"Emerging role of AMPA receptor subunit GluA1 in synaptic plasticity: Implications for Alzheimer\u2019s disease","volume":"54","author":"Qu","year":"2021","journal-title":"Cell Prolif."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.neuron.2013.03.016","article-title":"Modeling autism by SHANK gene mutations in mice","volume":"78","author":"Jiang","year":"2013","journal-title":"Neuron"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108104","DOI":"10.1016\/j.celrep.2020.108104","article-title":"An Epilepsy-Associated GRIN2A Rare Variant Disrupts CaMKII\u03b1 Phosphorylation of GluN2A and NMDA Receptor Trafficking","volume":"32","author":"Nguyen","year":"2020","journal-title":"Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1016\/j.cub.2005.08.069","article-title":"Activity-driven dendritic remodeling requires microtubule-associated protein 1A","volume":"15","author":"Szebenyi","year":"2005","journal-title":"Curr. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nm.4071","article-title":"Advancing the understanding of autism disease mechanisms through genetics","volume":"22","author":"Won","year":"2016","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e497","DOI":"10.1002\/mco2.497","article-title":"Autism spectrum disorder: Pathogenesis, biomarker, and intervention therapy","volume":"5","author":"Zhuang","year":"2024","journal-title":"MedComm"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Favre, M.R., Barkat, T.R., Lamendola, D., Khazen, G., Markram, H., and Markram, K. (2013). General developmental health in the VPA-rat model of autism. Front. Behav. Neurosci., 7.","DOI":"10.3389\/fnbeh.2013.00088"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.expneurol.2017.04.017","article-title":"The valproic acid-induced rodent model of autism","volume":"299","author":"Nicolini","year":"2018","journal-title":"Exp. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000509109","article-title":"A Systematic Review of the Valproic-Acid-Induced Rodent Model of Autism","volume":"42","author":"Chaliha","year":"2020","journal-title":"Dev. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Dougnon, G., and Matsui, H. (2025). Three decades of neuroscience research using animal models of ADHD and ASD: A bibliometric analysis. Front. Psychiatry, 16.","DOI":"10.3389\/fpsyt.2025.1528205"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zikopoulos, B., and Barbas, H. (2013). Altered neural connectivity in excitatory and inhibitory cortical circuits in autism. Front. Hum. Neurosci., 7.","DOI":"10.3389\/fnhum.2013.00609"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mapelli, L., Soda, T., D\u2019Angelo, E., and Prestori, F. (2022). The Cerebellar Involvement in Autism Spectrum Disorders: From the Social Brain to Mouse Models. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073894"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12974-014-0189-0","article-title":"GABAergic\/glutamatergic imbalance relative to excessive neuroinflammation in autism spectrum disorders","volume":"11","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nrn2286","article-title":"Pyramidal neurons: Dendritic structure and synaptic integration","volume":"9","author":"Spruston","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s11689-009-9023-x","article-title":"Common circuit defect of excitatory-inhibitory balance in mouse models of autism","volume":"1","author":"Gogolla","year":"2009","journal-title":"J. Neurodev. Disord."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15539","DOI":"10.1523\/JNEUROSCI.2671-15.2015","article-title":"Defects in Synaptic Plasticity, Reduced NMDA-Receptor Transport, and Instability of Postsynaptic Density Proteins in Mice Lacking Microtubule-Associated Protein 1A","volume":"35","author":"Takei","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4587","DOI":"10.1523\/JNEUROSCI.2757-14.2015","article-title":"Mutations in the microtubule-associated protein 1A (Map1a) gene cause Purkinje cell degeneration","volume":"35","author":"Liu","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13501","DOI":"10.1073\/pnas.0704391104","article-title":"Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid","volume":"104","author":"Rinaldi","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s43042-024-00527-0","article-title":"Identification of circRNA\u2013miRNA\u2013mRNA regulatory network associated to the autism spectrum disorder in children through integrated bioinformatics analysis","volume":"25","author":"Reiisi","year":"2024","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrneurol.2017.188","article-title":"Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders","volume":"14","author":"Sweeney","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nrneurol.2016.68","article-title":"Extracellular vesicles in neurodegenerative disease\u2014Pathogenesis to biomarkers","volume":"12","author":"Thompson","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"147ra111","DOI":"10.1126\/scitranslmed.3003748","article-title":"A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta","volume":"4","author":"Iliff","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1001\/jama.2013.2270","article-title":"Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism","volume":"309","author":"Christensen","year":"2013","journal-title":"JAMA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3178","DOI":"10.1038\/s41380-020-0748-y","article-title":"Autism spectrum heterogeneity: Fact or artifact?","volume":"25","author":"Mottron","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1158\/2767-9764.CRC-22-0190","article-title":"Diagnostic Accuracy of Blood-based Biomarkers for Pancreatic Cancer: A Systematic Review and Meta-analysis","volume":"2","author":"Kane","year":"2022","journal-title":"Cancer Res. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"106561","DOI":"10.4330\/wjc.v17.i7.106561","article-title":"Novel cardiac biomarkers and multiple-marker approach in the early detection, prognosis, and risk stratification of cardiac diseases","volume":"17","author":"Bokhari","year":"2025","journal-title":"World J. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41598-024-83742-4","article-title":"Multi-omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer development","volume":"15","author":"Kane","year":"2025","journal-title":"Sci. Rep."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/5\/478\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T15:23:50Z","timestamp":1777476230000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/5\/478"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["brainsci16050478"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16050478","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]}}}