PM346. Social defeat stress as juveniles impairs persistent social behaviors and neurogenesis

Objective: Accumulating data in the literature suggest that cytokines may be one of the factors influencing cognitive development of autism spectrum disorder (ASD). The present study investigated whether cytokines influence cognitive development in children with ASD. Methods: The Wechsler Intelligence Scale for Children (WISCIII or WISC-IV depending on the time of testing) was administered to 14 children with ASD (9 boys and 5 girls; mean age (standard deviation) = 11.6 (2.1) years). The serum levels of 10 cytokines (granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor-α) were examined using the Human Ultrasensitive Cytokine Magnetic 10-Plex Panel for the Luminex platform. Each serum sample was assayed in duplicate, and all samples were run on the same assay. The relationships between WISC scores and serum levels of the cytokines were examined. Results: The serum level of IL-6 was significantly negatively correlated with IQ in children who were administered the WISC-III (p < 0.001) as well as in those administered the WISC-IV (p < 0.01). Significant correlation of serum IL-6 levels with IQ was also observed when children administered the WISC-III and those administered the WISC-IV were analyzed together (p < 0.001). No other cytokines were significantly correlated with IQ. Conclusions: The present results suggest that peripheral IL-6 levels are negatively correlated with cognitive development in children with ASD. Although the mechanisms underlying the association between cytokines and cognitive development remain to be clarified, our preliminary findings add to the evidence that cytokines may be involved in the neural development of ASD. PM345 Resveratrol Suppresses Neuroinflammation in the Experimental Paradigm of Autism Spectrum Disorders Ranjana Bhandari, Anurag Kuhad University Institute Of Pharmaceutical Sciences, Panjab University, India Abstract Objective: Neuroinflammation triggered by the stimulation of matrix metalloproteinases and the subsequent release of proinflammatory cytokines, as a result of oxidative stress and mitochondrial dysfunction, leads to neuronal dysfunction and is one of the probable mechanisms involved in the pathogenesis of autism spectrum disorders (ASD). The aim of the present study was to explore the ameliorative potential of resveratrol on neuroinflammation in the experimental paradigm of neuroinflammatory model of ASD in rats. Method: 1M Propanoic acid (PPA)(4μl) was infused over 10 minutes into the anterior portion of the lateral ventricle to induce ASD like symptoms in rats. Resveratrol (5, 10 and 15 mg/kg) was administered starting from the 2nd day of the surgery and continued upto 28th day. Rats were tested for various behavioural paradigms such as social interaction, stereotypy, locomotor activity, anxiety and novelty, depression, spatial learning and memory, repetitive and pervasive behaviour between the 7th day and 28th day. In addition, biochemical tests for oxidative stress, mitochondrial complexes, TNF-α and MMP-9 were also assessed. Results: Intracerebroventricular injection of propanoic acid produced neurological, sensory, behavioural, biochemical and molecular deficits which were assessed as endophenotypes of autism spectrum disorders. Continued treatment with resveratrol for four weeks restored, significantly and dose dependently, all these endophenotypes in PPA induced ASD in rats. Conclusion: The major finding of the study is that resveratrol restored the core and associated symptoms of autistic phenotype by suppressing oxidative-nitrosative stress, mitochondrial dysfunction, TNF-α and MMP-9 expression in PPA induced ASD in rats. Therefore, resveratrol might serve as an adjunct potential therapeutic agent for amelioration of neurobehavioural and biochemical deficits associated with autism spectrum disorders.