{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:58:16Z","timestamp":1792112296275,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":24,"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":["82173535"],"award-info":[{"award-number":["82173535"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["No.LH2023H017"],"award-info":[{"award-number":["No.LH2023H017"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Emerging evidence suggests lipid metabolism dysregulation contributes to autism spectrum disorders (ASD), with the endocannabinoid system (cannabinoid receptors CB1R\/CB2R) implicated in lipid homeostasis. This study investigated whether CB1R\/CB2R activation improves hippocampal lipid metabolism and ASD\u2010like behaviors in a valproic acid (VPA)\u2010induced ASD rat model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male offspring from dams exposed to VPA (600\u2009mg\/kg, i.p.) received the CB1R agonist ACPA (0.1\u2009mg\/kg) or the CB2R agonist AM1241 (3\u2009mg\/kg) from postnatal days 21\u201327. ASD\u2010like behaviors (marble burying, self\u2010grooming, social interaction, open\u2010field tests) and hippocampal lipid profiles (UPLC\u2010MS\/MS) were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>VPA\u2010exposed rats displayed heightened repetitive behaviors, social deficits, and hyperactivity, all significantly alleviated by ACPA and AM1241. Lipidomics revealed marked reductions in hippocampal phosphatidylcholines, lysophosphatidylcholines, fatty acids, sphingomyelins, ceramides, and phosphatidylethanolamines in VPA rats. Both agonists restored lipid levels to near normal, comparable to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CB1R\/CB2R activation ameliorates behavioral abnormalities and rectifies hippocampal lipid dysregulation in VPA\u2010induced ASD models, highlighting cannabinoid receptors as potential therapeutic targets for ASD\u2010associated metabolic disturbances.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70591","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T11:01:35Z","timestamp":1756119695000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cannabinoid Receptors <scp>CB1<\/scp> and <scp>CB2<\/scp> Activation Restores Hippocampal Lipid Profiles and Alleviates Autism\u2010Like Behaviors in Valproic Acid\u2010Induced <scp>ASD<\/scp> Rats"],"prefix":"10.1111","volume":"31","author":[{"given":"Haoran","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Children's and Adolescent Health, Public Health College Harbin Medical University  Harbin China"},{"name":"Heilongjiang Province Key Laboratory of Child Development and Genetic Research Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Children's and Adolescent Health, Public Health College Harbin Medical University  Harbin China"},{"name":"Heilongjiang Province Key Laboratory of Child Development and Genetic Research Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Children's and Adolescent Health, Public Health College Harbin Medical University  Harbin 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