{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:55:18Z","timestamp":1790664918719,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005756","name":"Shahrekord University of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005756","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004305","name":"Shahroud University of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004305","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Neurobiology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with rising global prevalence and no effective pharmacological treatments. Early\u2010life stress, such as maternal separation (MS), is a known risk factor that can lead to neuroinflammation and oxidative stress, contributing to autistic\u2010like behaviors. This study addresses the knowledge gap by exploring the potential of\n                    <jats:italic>Morus nigra<\/jats:italic>\n                    L. (black mulberry) extract, known for its anti\u2010inflammatory and antioxidant properties, in mitigating these behaviors in a mouse model of MS. In this study, 40 male NMRI mice were used. Hydroalcoholic extract of\n                    <jats:italic>M. nigra<\/jats:italic>\n                    was isolated by maceration method; then, it was administered to MS\u2010exposed mice (20, 40, or 60\u00a0mg\/kg), and its effects on social interaction, memory, aggression, and spatial learning were assessed by using behavioral tests, including a three\u2010chamber test, resident\u2010intruder test, shuttle box test, and Morris water maze test. Oxidative stress markers in the serum and hippocampus as well as gene expression of inflammatory mediators in the hippocampus were assessed. Behavioral tests revealed significant improvements in social preference and passive avoidance memory and reduced aggressive behaviors. The Morris Water Maze test indicated enhanced spatial learning and memory. Biochemically,\n                    <jats:italic>M. nigra<\/jats:italic>\n                    extract reduced malondialdehyde levels and nitrite levels and increased total antioxidant capacity in the hippocampus. Gene expression analysis showed decreased levels of pro\u2010inflammatory cytokines, including\n                    <jats:italic>Tnf\u2010\u03b1<\/jats:italic>\n                    ,\n                    <jats:italic>Il\u20101\u03b2<\/jats:italic>\n                    , and\n                    <jats:italic>Tlr4<\/jats:italic>\n                    . These findings suggest that\n                    <jats:italic>M. nigra<\/jats:italic>\n                    extract mitigates autistic\u2010like behaviors in MS mice by possibly attenuating neuroinflammation and oxidative stress, highlighting its potential for further investigation in ASD\u2010related behavioral phenotypes. Further research is warranted to elucidate the precise mechanisms and optimize dosing strategies.\n                  <\/jats:p>","DOI":"10.1002\/dneu.70066","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:54:27Z","timestamp":1790661267000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Morus nigra<\/i>\n                    L. Extract Mitigates Autistic\u2010Like Behaviors in Maternally Separated Mice: Potential Involvement of Neuroinflammation, Nitric Oxide, and Oxidative Stress"],"prefix":"10.1002","volume":"86","author":[{"given":"Fariba","family":"Azadikhah","sequence":"first","affiliation":[{"name":"Student Research Committee Shahrekord University of Medical Sciences  Shahrekord Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Amini\u2010Khoei","sequence":"additional","affiliation":[{"name":"Medical Plants Research Center, Basic Health Sciences Institute Shahrekord University of Medical Sciences  Shahrekord Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Lorigooini","sequence":"additional","affiliation":[{"name":"Medical Plants Research Center, Basic Health Sciences Institute Shahrekord University of Medical Sciences  Shahrekord Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyedeh Maryam","family":"Kazemi","sequence":"additional","affiliation":[{"name":"Medical Plants Research Center, Basic Health Sciences Institute Shahrekord University of Medical Sciences  Shahrekord Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Bijad","sequence":"additional","affiliation":[{"name":"Medical Plants Research Center, Basic Health Sciences Institute Shahrekord University of Medical Sciences  Shahrekord Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein Tahmasebi","family":"Dehkordi","sequence":"additional","affiliation":[{"name":"Student Research Committee Shahrekord University of Medical Sciences  Shahrekord Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Rahimi\u2010Madiseh","sequence":"additional","affiliation":[{"name":"Medical Plants Research Center, Basic Health Sciences Institute Shahrekord University of Medical Sciences  Shahrekord Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.715354","article-title":"Rivaroxaban Modulates TLR4\/Myd88\/NF\u2010K\u03b2 Signaling Pathway in a Dose\u2010Dependent Manner with Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression","volume":"12","author":"Abdelzaher W. 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Fruit Extract","volume":"16","author":"Aleebrahim\u2010Dehkordy E.","year":"2019","journal-title":"Journal of Dietary Supplements"},{"issue":"4","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1080\/24750573.2018.1470360","article-title":"Assessment of Malondialdehyde Levels, Superoxide Dismutase, and Catalase Activity in Children With Autism Spectrum Disorders","volume":"28","author":"Altun H.","year":"2018","journal-title":"Psychiatry and Clinical Psychopharmacology"},{"issue":"8","key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1038\/s41380-018-0113-6","article-title":"Shank3 Mutation in a Mouse Model of Autism Leads to Changes in the S\u2010Nitroso\u2010Proteome and Affects Key Proteins Involved in Vesicle Release and Synaptic Function","volume":"25","author":"Amal H.","year":"2020","journal-title":"Molecular Psychiatry"},{"issue":"4","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jtcme.2023.02.005","article-title":"Hydroalcoholic Extract of Passiflora Incarnata Improves the Autistic\u2010Like Behavior and Neuronal Damage in a Valproic Acid\u2010Induced Rat Model of Autism","volume":"13","author":"Amini F.","year":"2023","journal-title":"Journal of Traditional and Complementary Medicine"},{"key":"e_1_2_12_8_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.npep.2019.101942","article-title":"Possible Involvement of PI3K\/AKT\/mTOR Signaling Pathway in the Protective Effect of Selegiline (Deprenyl) Against Memory Impairment Following Ischemia Reperfusion in Rat","volume":"77","author":"Amini\u2010Khoei H.","year":"2019","journal-title":"Neuropeptides"},{"issue":"2","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.34172\/fnp.196","article-title":"Effects of Ruta graveolens L. on Locomotor Disorders and Anxiety: Modulation of Hippocampal Antioxidant Capacity","volume":"10","author":"Asgharzadeh N.","year":"2025","journal-title":"Future Natural Products"},{"key":"e_1_2_12_10_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.mce.2020.111125","article-title":"Long Term Effects of Early Life Stress on HPA Circuit in Rodent Models","volume":"521","author":"Babicola L.","year":"2021","journal-title":"Molecular and Cellular Endocrinology"},{"key":"e_1_2_12_11_1","first-page":"77","volume-title":"Measurement of Antioxidant Activity & Capacity","author":"Benzie I. 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