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This study evaluates the therapeutic potential of transauricular vagal nerve stimulation (tVNS) in a valproic acid (VPA)\u2010induced mouse model of ASD. The study comprised three groups: the control\u00a0+\u00a0sham (saline\u2010treated offsprings receiving sham stimulation), the autistic\u00a0+\u00a0sham (VPA\u2010treated offspring receiving sham stimulation), and the autistic\u00a0+\u00a0tVNS (VPA\u2010treated offsprings receiving tVNS). Male C57BL\/6 mice exposed to VPA on embryonic day 12.5 were evaluated for behavioral and neurobiological alterations. tVNS was applied twice weekly for 3 weeks to investigate its effects on sociability, anxiety\u2010like behaviors, neurogenesis markers, and apoptosis pathways. Behavioral testing, including the three\u2010chamber test, mirrored chamber test, open field test, and elevated plus maze, revealed that tVNS significantly improved sociability and social preference indices, reduced social anxiety, and decreased general anxiety\u2010like behaviors in VPA\u2010induced mice. Histological and immunohistochemical analyses have shown a decrease in neuron density, brain\u2010derived neurotrophic factor (BDNF), and doublecortin (DCX) expression in the hippocampus, amygdala, and prefrontal cortex of VPA\u2010induced mice. Additionally, the increase in caspase\u20103 immunoreactivity indicates increased apoptosis. tVNS treatment restored BDNF and DCX levels, promoting neurogenesis and synaptic plasticity while significantly reducing caspase\u20103\u2010mediated apoptosis in affected brain regions. These findings suggest that tVNS may counteract the neural and behavioral deficits associated with ASD by modulating neurogenesis, neuronal plasticity, and apoptosis. The study highlights tVNS as a potential therapeutic intervention for ASD, emphasizing its role in targeting both behavioral alterations and underlying neurobiological mechanisms.<\/jats:p>","DOI":"10.1002\/dneu.23019","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T07:38:47Z","timestamp":1763797127000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Brain Plasticity: Vagal Nerve Stimulation as a Therapy for Autism\u2010Like Symptoms in a Valproic Acid Mouse Model"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0313-1906","authenticated-orcid":false,"given":"Aysen","family":"Calikusu","sequence":"first","affiliation":[{"name":"Neuroscience and Neurotechnology Center of Excellence Gazi University  Ankara 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