{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:56:15Z","timestamp":1790553375660,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication deficits and repetitive behaviours. Emerging evidence highlights neuroinflammation, oxidative stress and mitochondrial dysfunction in its pathogenesis. Propionic acid (PPA), an enteric short\u2010chain fatty acid, is frequently utilized to replicate ASD\u2010like phenotypes in rodents. This study investigated the therapeutic efficacy of pioglitazone, a peroxisome proliferator\u2010activated receptor gamma (PPAR\u2010\u03b3) agonist known for its neuroprotective and anti\u2010inflammatory properties, in a PPA\u2010induced rat model of ASD. Thirty male Wistar rats were randomly assigned to control, PPA\u2009+\u2009saline or PPA\u2009+\u2009pioglitazone (15\u2009mg\/kg\/day, orally) groups. Neurobehavioural profiling utilized the sociability, open\u2010field and passive avoidance learning tests. Furthermore, cerebral tissues were analysed for tumour necrosis factor\u2010alpha (TNF\u2010\u03b1), brain\u2010derived neurotrophic factor (BDNF), sirtuin\u20101 (SIRT1), galectin\u20103 and malondialdehyde (MDA), alongside comprehensive histopathological evaluations of the hippocampus and cerebellum. Pioglitazone significantly improved social interaction, associative memory retention and spontaneous locomotor activity. Biochemically, the treatment significantly suppressed inflammatory and oxidative stress markers (TNF\u2010\u03b1, galectin\u20103 and MDA) while increasing cerebral BDNF and SIRT1 levels. Histological assessments confirmed these neuroprotective benefits, demonstrating preserved neuronal architecture and decreased glial fibrillary acidic protein (GFAP) immunoreactivity, indicative of reduced reactive astrogliosis. These findings indicate that pioglitazone ameliorates behavioural, biochemical and histopathological alterations in the PPA\u2010induced rat model of ASD. The concurrent restoration of cerebral SIRT1 levels suggests that SIRT1\u2010related signalling may contribute to the observed neuroprotective effects.<\/jats:p>","DOI":"10.1002\/jdn.70180","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:15:16Z","timestamp":1790550916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Potential of Pioglitazone in a Propionic Acid\u2010Induced Rat Model of Autism Spectrum Disorder: The Role of the SIRT1\/PPAR\u2010\u03b3 Axis"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2488-2012","authenticated-orcid":false,"given":"Arife","family":"Erdo\u011fan","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine Health Sciences University \u0130zmir Tepecik Education and Research Hospital  Izmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0048-444X","authenticated-orcid":false,"given":"M\u00fcmin Alper","family":"Erdo\u011fan","sequence":"additional","affiliation":[{"name":"Department of Physiology Izmir Katip \u00c7elebi University, Faculty of Medicine  Izmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-0522","authenticated-orcid":false,"given":"Yi\u011fit","family":"Uyan\u0131kgil","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology Ege University, Faculty of Medicine  Izmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oytun","family":"Erba\u015f","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, BAMER Biruni University  Istanbul T\u00fcrkiye"},{"name":"Department of Physiology Demiroglu Bilim University, Faculty of Medicine  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S367229"},{"issue":"2","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1124\/pr.111.005108","article-title":"Brain\u2010Derived Neurotrophic Factor and Neuropsychiatric Disorders","volume":"64","author":"Autry A. 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