The Ameliorative Effect of Spirulina platensis as Add-On Therapy to Risperidone on Valproic Acid-Induced Autism in Rat Pups: Implication of Oxidative Stress, Inflammatory, and ERK-1/2 Signaling Pathway.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Prenatal exposure to valproic acid (VPA), a teratogenic antiepileptic agent, is known to induce ASD-like symptoms in animal models. This study aimed to assess the therapeutic effects of Spirulina platensis (SP) and Risperidone (Ris) in a VPA-induced autism rat model. Pregnant Wistar rats received a single intraperitoneal dose of VPA (600 mg/kg) on gestational day 12.5. Male offspring received SP (200 mg/kg, p.o.), and/or Ris (1 mg/kg, p.o.), and combination group(Ris+SP) via oral gavage from postnatal day (PND) 23 to PND 52. Behavioral evaluations were performed on PND 52, and biochemical, molecular, and histological analyses were conducted on PND 61, following decapitation. Oxidative stress markers (malondialdehyde [MDA], superoxide dismutase [SOD]), inflammatory cytokines (IL-1β, tumor necrosis factor-alpha [TNF-α]), and extracellular signal-regulated kinase (ERK) protein expression were measured. Nissl staining was used to assess neuronal loss in the prefrontal cortex (PFC). VPA exposure induced anxiety-like behaviors, repetitive actions, impaired social interactions, increased MDA levels, decreased SOD activity, upregulated ERK signaling, elevated IL-1β and TNF-α levels, and neuronal loss in the PFC. Treatment with SP and/or Ris alleviated these deficits, improving behavioral abnormalities, oxidative stress, inflammatory markers, and histological alterations. Combined SP and Ris treatment provided neuroprotective and behavioral improvements in the VPA-induced ASD model, suggesting potential therapeutic roles for ASD interventions.