Neuropsychopharmacotherapeutic efficacy of curcumin in experimental paradigm of autism spectrum disorders

Aim: Neuroinflammatory response triggered by the stimulation of matrix metalloproteinases plays a pivotal role in the development of autistic phenotype. MMPs stimulate inflammatory cytokines release along with mitochondrial deficits that ultimately lead to neuronal dysfunction and precipitate autistic symptoms. The aim of the present study was to explore the neuropsychopharmacotherapeutic efficacy of curcumin in the experimental paradigm of autism spectrum disorders. Materials and methods: 1 M propanoic acid (4 mu l) was infused over 10 min into the anterior portion of the caudoputamen to induce autistic behavior in rats. Curcumin (50, 100 and 200 mg/kg) was administered per orally starting from 2nd day of surgery and continued up to 28th day. Rats were tested for various neurobehavioural paradigms like social interaction, stereotypy, locomotor activity, anxiety, novelty, depression, spatial learning and memory as well as for repetitive and pervasive behavior. In addition, biochemical tests for oxidative stress, mitochondrial complexes, TNF-alpha and MMP-9 were also carried out. Key findings: Intracerebroventricular injection of propanoic acid produced neurological, sensory, behavioral, biochemical and molecular deficits which were assessed as endophenotype of autism spectrum disorders. Regular treatment with curcumin for four weeks significantly and dose dependently restored neurological, behavioral, biochemical and molecular changes associated with autistic phenotype in rats. Significance: The major finding of the study is that curcumin restored the core and associated symptoms of autistic phenotype by suppressing oxidative-nitrosative stress, mitochondrial dysfunction, TNF-alpha and MMP-9 in PPAinduced autism in rats. Therefore, curcumin can be developed as a potential neuropsychopharmacotherapeutic adjunct for autism spectrum disorders (ASD). (C) 2015 Elsevier Inc. All rights reserved.