Prodigiosin-conjugated silver nanoparticles target neuroimmune dysregulation and pro-inflammatory cytokines TNF-α, IL-1β/NF-kB pathways in an autistic model of rat pups
ABSTRACT Autism spectrum disorder (ASD) is associated with neuroimmune dysregulation and elevated pro-inflammatory cytokines. This study explores the therapeutic potential of prodigiosin-conjugated silver nanoparticles (PG-AgNPs) in targeting these pathways in an autistic rat model. Autistic-like behavior was induced in rat pups through prenatal exposure to valproic acid (VPA) (600mg/kg). The treatment with PG-AgNPs (3mg/kg) has been applied for 7 days in rat pups after birth. Induction of autism by VPA decreased the level of 5-HT, DA, NE, GABA, glycine and taurine in cerebellum and cerebral cortex as well as reduction in brain cholesterol and antioxidants enzymes (GSH, SOD and CAT). However, it showed a significant increase in MAO, AChE, glutamate, aspartate, serine and lipid peroxidation. The inflammatory mediators NF-kB, TNF-α and IL-1β were increased and enhancing apoptotic markers (Bax, Bcl2) and reduce anti-apoptotic (Caspase-3) in brain tissue. PG-AgNPs treatment markedly reduced these inflammatory markers, restored neurotransmitter balance, and improved antioxidant defenses. Additionally, PG-AgNPs attenuated oxidative stress and modulated apoptotic markers. PG-AgNPs demonstrated significant neuroprotective, anti-inflammatory, and antioxidant effects in the autistic rat model, suggesting their potential as a nanotherapeutic approach for ASD. Further studies are needed to validate their long-term efficacy.