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Metformin has emerged as a candidate for drug repurposing in ASD due to its metabolic and neurobiological actions. This study evaluated the in vivo effects of metformin (400\u00a0mg\/kg, orally) administered from postnatal day 21 to 35 (PND21\u201335) in male and female offspring of mice prenatally exposed to valproic acid (VPA; 450\u00a0mg\/kg, i.p.) on gestational day 12.5 (GD12.5). Behavioral tests included the open field, elevated plus maze, Y\u2010maze, three\u2010chamber social interaction, and self\u2010grooming. The prefrontal cortex (PFC) and hippocampus (HPC) were analyzed for oxidative stress markers (malondialdehyde [MDA], reduced glutathione [GSH]), total protein content, and acetylcholinesterase (AChE) activity. In vivo, metformin attenuated several VPA\u2010associated behavioral alterations, including changes in locomotor\/exploratory activity and repetitive behavior, with additional effects on anxiety\u2010like behavior, sociability, and spatial working memory that varied according to sex and behavioral parameter. Biochemical analyses showed metformin\u2010associated changes in GSH and MDA that varied across sexes and brain regions. VPA\u2010induced increases in PFC AChE activity were attenuated by metformin in both sexes. Total protein content also varied according to sex and brain region. These findings provide preclinical evidence that metformin can attenuate behavioral alterations associated with prenatal VPA exposure and modulate oxidative stress\u2010related markers, with patterns varying across sexes and brain regions.<\/jats:p>","DOI":"10.1002\/dneu.70061","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:39:36Z","timestamp":1789713576000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metformin Attenuates Behavioral Deficits and Oxidative Stress in a Preclinical Model of Autism"],"prefix":"10.1002","volume":"86","author":[{"given":"Madna Costa","family":"Freitas","sequence":"first","affiliation":[{"name":"Superior Institute of Biomedical Sciences State University of Cear\u00e1 (UECE)  Fortaleza Cear\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00ea Felipe 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