Ranjana Bhandari1, Anurag Kuhad2. 1. Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh 160 014 India. Electronic address: akb10in@yahoo.co.uk. 2. Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh 160 014 India. Electronic address: anurag_pu@yahoo.com.
Abstract
BACKGROUND: Neuronal dysfunction caused by neuroinflammation triggered by the stimulation of matrix metalloproteinases and the subsequent release of pro-inflammatory cytokines, as a result of oxidative stress and mitochondrial dysfunction, 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) (4 μl) was infused over 10 min 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, novelty, depression, spatial learning, 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: Treatment with resveratrol for four weeks restored, significantly and dose dependently, all the neurological, sensory, behavioural, biochemical and molecular deficits in PPA induced autistic phenotype 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.
BACKGROUND:Neuronal dysfunction caused by neuroinflammation triggered by the stimulation of matrix metalloproteinases and the subsequent release of pro-inflammatory cytokines, as a result of oxidative stress and mitochondrial dysfunction, 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) (4 μl) was infused over 10 min 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, novelty, depression, spatial learning, 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: Treatment with resveratrol for four weeks restored, significantly and dose dependently, all the neurological, sensory, behavioural, biochemical and molecular deficits in PPA induced autistic phenotype 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.
Authors: Ekaterina A Trifonova; Alexandra I Klimenko; Zakhar S Mustafin; Sergey A Lashin; Alex V Kochetov Journal: Int J Mol Sci Date: 2019-12-15 Impact factor: 5.923
Authors: Nils Leander Huamán-Castilla; María Salomé Mariotti-Celis; Maximiliano Martínez-Cifuentes; José Ricardo Pérez-Correa Journal: Biomolecules Date: 2020-03-20