Nesfatin1 attenuates autism-like behavior via antioxidant, anti-inflammatory activities in a prenatal valproic acid-induced rat model of autism.

Nesfatin1, a multifunctional peptide involved in energy homeostasis and neural regulation, has emerged as a promising candidate for modulating neurodevelopmental disorders. The anti-inflammatory, antioxidant, and neuroprotective properties of Nesfatin1 have been proven in the central nervous system (CNS). Therefore, it has emerged as a candidate for targeted therapy of various neurological condition. Autism Spectrum Disorder (ASD) is a significant neurological disorder. Considering the importance of these mechanisms demonstrated by Nefastine1, The current study aimed to investigate the therapeutic potential and mechanisms of Nesfatin1 in a rat model of autism. This study evaluated the therapeutic potential of Nesfatin1 in a rodent model of autism induced by prenatal exposure to valproic acid (VPA). Pregnant Wistar rats received VPA on embryonic day 12.5, and male offspring were subsequently assessed for autism-like behaviors using a comprehensive battery of tests, including the three-chamber social interaction test, marble burying, shuttle box passive avoidance, and the elevated plus maze. Following behavioral testing, rats were euthanized, and blood samples were collected via transcardial perfusion. Serum oxytocin levels were measured, and hippocampal tissues were analyzed for inflammatory markers (IL-6, TNF-α) using ELISA. Additionally, total antioxidant capacity (TAC) and the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were assessed. VPA-exposed rats exhibited significant social deficits, increased repetitive behaviors, and impaired cognitive performance, accompanied by heightened neuroinflammation and oxidative stress. Notably, treatment with Nesfatin1 markedly improved social engagement and preference, reduced anxiety and repetitive behaviors, and restored biochemical parameters toward normal levels. Results showed that possible therapeutic mechanism of Nefastin1 are by decreasing inflammation and reducing markers of oxidative stress, while concurrently elevating levels of oxytocin, in addition to the other unknown mechanisms.