{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:56:17Z","timestamp":1790211377956,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T00:00:00Z","timestamp":1718755200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371030"],"award-info":[{"award-number":["32371030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071395"],"award-info":[{"award-number":["82071395"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101466"],"award-info":[{"award-number":["82101466"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Discovery"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by impaired social interactions and communication, repetitive, or stereotyped behavior. Docosahexaenoic acid (DHA), an essential polyunsaturated fatty acid, has been demonstrated to exert anti\u2010oxidative stress and anti\u2010inflammatory properties, while also promoting myelin development and neural differentiation and development. However, it remains uncertain whether DHA can ameliorate autistic\u2010like behaviors, and if so, the underlying mechanisms are still unclear. Here, we established a neonatal maternal separation (NMS) rat model and treated it with DHA (80\u00a0mg\/kg\/day, i.p.). The results showed DHA treatment significantly alleviated autism\u2010like behaviors in the NMS rats during their juvenile period. Subsequently, we employed network pharmacology analysis and molecular docking methods to screen potential targets of DHA in ASD therapy. Through Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Wikipedia enrichment analysis, we identified anti\u2010oxidative stress, anti\u2010inflammatory and JNK signaling pathway that might be associated with DHA\u2010mediated improvement of autistic\u2010like behaviors. Furthermore, western blotting assays showed DHA significantly downregulated the expression levels of p\u2010JNK and c\u2010JUN, while upregulating the expression levels of NRF2, HO\u20101, SOD1, and CAT. In addition, enzyme\u2010linked immunosorbent assay results showed DHA effectively reduced the production of pro\u2010inflammatory factors, such as TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2. Collectively, our study predicted and validated that DHA exhibits the potential to improve autistic\u2010like behaviors induced by NMS in rats by suppressing JNK activation and inhibiting oxidative stress and inflammatory response. These findings suggest that DHA may be a potential therapeutic agent for the treatment of ASD.<\/jats:p>","DOI":"10.1002\/pdi3.91","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T09:07:50Z","timestamp":1718788070000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Docosahexaenoic acid ameliorates autistic\u2010like behaviors by inhibiting oxidative stress and inflammatory response in neonatal maternal separation rats"],"prefix":"10.1002","volume":"3","author":[{"given":"Boqing","family":"Xu","sequence":"first","affiliation":[{"name":"Growth, Development, and Mental Health of Children and Adolescence Center Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and Disorders Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yuan","sequence":"additional","affiliation":[{"name":"Growth, Development, and Mental Health of Children and Adolescence Center Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and Disorders Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohuan","family":"Li","sequence":"additional","affiliation":[{"name":"Growth, Development, and Mental Health of Children and Adolescence Center Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and Disorders Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyang","family":"Yu","sequence":"additional","affiliation":[{"name":"Growth, Development, and Mental Health of Children and Adolescence Center Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and Disorders Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfang","family":"Dai","sequence":"additional","affiliation":[{"name":"Growth, Development, and Mental Health of Children and Adolescence Center Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and Disorders Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Department of Children Health Care Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifang","family":"Dong","sequence":"additional","affiliation":[{"name":"Growth, Development, and Mental Health of Children and Adolescence Center Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and Disorders Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.042457199"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2020-0923"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/10538711003615038"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-01742-2"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065487"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2012.61"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2009.03.011"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12014-017-9138-0"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066418"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/cap.2015.0159"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093293"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-8994(97)00045-3"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(98)00021-6"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.05.024"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199808000-00011"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2104689118"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14194136"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000482"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu5072777"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/phrs.1999.0495"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2022.04.015"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20174240"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/1028415X.2019.1580918"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)32132-5"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300218200"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05433-7"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2021.131755"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.118"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109381"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2017.12.001"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2008.07.003"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1021"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpbi.5"},{"issue":"1","key":"e_1_2_11_36_1","first-page":"D845","article-title":"The DisGeNET knowledge platform for disease genomics: 2019 update","volume":"48","author":"Pi\u00f1ero J","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac194"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbac261"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1038"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-010-9352-6"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5196302"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2022.800079"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2020.153241"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3729"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2013.08.004"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2015.11.009"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.859198"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2022.12.001"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.111826"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12123615"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23094635"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06335.x"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2023.101254"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502903102"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00272"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3141"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20123038"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.07.017"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2016.08.005"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.34067\/KID.0000000000000152"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2017.04.009"}],"container-title":["Pediatric Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pdi3.91","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T19:17:40Z","timestamp":1767122260000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pdi3.91"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,19]]},"references-count":63,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/pdi3.91"],"URL":"https:\/\/doi.org\/10.1002\/pdi3.91","archive":["Portico"],"relation":{},"ISSN":["2835-558X","2835-5598"],"issn-type":[{"value":"2835-558X","type":"print"},{"value":"2835-5598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,19]]},"assertion":[{"value":"2024-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e91"}}