{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T07:04:29Z","timestamp":1785135869350,"version":"3.55.0"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012021","name":"Iran University of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012021","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Neurobiology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Prenatal exposure to valproic acid (VPA), a teratogenic antiepileptic agent, is known to induce ASD\u2010like symptoms in animal models. This study aimed to assess the therapeutic effects of\n                      <jats:italic>Spirulina platensis<\/jats:italic>\n                      (SP) and Risperidone (Ris) in a VPA\u2010induced autism rat model. Pregnant Wistar rats received a single intraperitoneal dose of VPA (600\u00a0mg\/kg) on gestational day 12.5. Male offspring received SP (200\u00a0mg\/kg, p.o.), and\/or Ris (1\u00a0mg\/kg, p.o.), and combination group(Ris+SP)\u00a0via oral gavage from postnatal day (PND) 23 to PND 52. Behavioral evaluations were performed on PND 52, and biochemical, molecular, and histological analyses were conducted on PND 61, following decapitation. Oxidative stress markers (malondialdehyde [MDA], superoxide dismutase [SOD]), inflammatory cytokines (IL\u20101\u03b2, tumor necrosis factor\u2010alpha [TNF\u2010\u03b1]), and extracellular signal\u2010regulated kinase (ERK) protein expression were measured. Nissl staining was used to assess neuronal loss in the prefrontal cortex (PFC). VPA exposure induced anxiety\u2010like behaviors, repetitive actions, impaired social interactions, increased MDA levels, decreased SOD activity, upregulated ERK signaling, elevated IL\u20101\u03b2 and TNF\u2010\u03b1 levels, and neuronal loss in the PFC. Treatment with SP and\/or Ris alleviated these deficits, improving behavioral abnormalities, oxidative stress, inflammatory markers, and histological alterations. Combined SP and Ris treatment provided neuroprotective and behavioral improvements in the VPA\u2010induced ASD model, suggesting potential therapeutic roles for ASD interventions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dneu.70052","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:00:36Z","timestamp":1783076436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Ameliorative Effect of\n                    <i>Spirulina platensis<\/i>\n                    as Add\u2010On Therapy to Risperidone on Valproic Acid\u2010Induced Autism in Rat Pups: Implication of Oxidative Stress, Inflammatory, and ERK\u20101\/2 Signaling Pathway"],"prefix":"10.1002","volume":"86","author":[{"given":"Setareh","family":"Dehkhodaei","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Biological Sciences Kharazmi University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdolhamid","family":"Angaji","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Biological Sciences Kharazmi University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Negin","family":"Khosravipour","sequence":"additional","affiliation":[{"name":"Neuromusculoskeletal Research Center Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Karamali","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Allied Medicine Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mosayeb","family":"Pashaee","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soroush","family":"Taherkhani","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razieh","family":"Hajisoltani","sequence":"additional","affiliation":[{"name":"Physiology Research Center Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2010.03658.x"},{"issue":"7","key":"e_1_2_13_3_1","article-title":"Exploring the Neuroprotective Effects of Spirulina platensis: Insights into Hemorrhagic Volume and Histological Outcomes","volume":"15","author":"Almeida T.","year":"2023","journal-title":"Cureus"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2021.113432"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2004.11.001"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.06.015"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7174351"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.48.1.182"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-03941-y"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/2019036"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.02.047"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000048665"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11175100"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2022.110522"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.11.1652"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066418"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/2058738418785514"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4703-9"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02245607"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.21037\/tp.2019.09.09"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12567"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-022-00521-6"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01081-0"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072682"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.046987"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01072.2005"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.154.4.580b"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms130810608"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-012-0722-8"},{"key":"e_1_2_13_30_1","volume-title":"Pre\u2010Clinical Models: Techniques and Protocols","author":"Kraeuter A.\u2010K.","year":"2018"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8863256"},{"issue":"6","key":"e_1_2_13_32_1","first-page":"389","article-title":"Pharmacological Therapies for Autism Spectrum Disorder: A Review","volume":"40","author":"LeClerc S.","year":"2015","journal-title":"Pharmacy and Therapeutics"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1633680"},{"issue":"126","key":"e_1_2_13_34_1","article-title":"Novel Object Recognition Test for the Investigation of Learning and Memory in Mice","author":"Lueptow L. M.","year":"2017","journal-title":"Journal of Visualized Experiments: JoVE"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.5607\/en.2015.24.4.285"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145711001775"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci10030163"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0218937"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.10.063"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.7.489"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2019.03.004"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16050769"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1992.tb01417.x"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2014.03.007"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9121186"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00150"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.15419\/bmrat.v5i9.477"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2349-11.2011"},{"issue":"4","key":"e_1_2_13_49_1","first-page":"1847","article-title":"Spirulina platensis (Blue\u2010Green Algae): A Miracle From Sea Combats the Oxidative Stress and Improves Behavioral Deficits in an Animal Model of Schizophrenia","volume":"33","author":"Shahzad S.","year":"2020","journal-title":"Pakistan Journal of Pharmaceutical Sciences"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.12.009"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1249-19.2019"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1346"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065487"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1253842"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1819.2004.01229.x"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.04.038"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep10252"}],"container-title":["Developmental Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dneu.70052","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/dneu.70052","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dneu.70052","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:51:41Z","timestamp":1785135101000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dneu.70052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/dneu.70052"],"URL":"https:\/\/doi.org\/10.1002\/dneu.70052","archive":["Portico"],"relation":{},"ISSN":["1932-8451","1932-846X"],"issn-type":[{"value":"1932-8451","type":"print"},{"value":"1932-846X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70052"}}