title: Neuropsychopharmacotherapeutic efficacy of curcumin in experimental paradigm of autism spectrum disorders.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  1M propanoic acid (4μl) was infused over 10min into the anterior portion of the caudoputamen to induce autistic behavior in rats. Curcumin (50, 100 and 200mg/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-α and MMP-9 were also carried out.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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-α and MMP-9 in PPA-induced autism in rats. Therefore, curcumin can be developed as a potential neuropsychopharmacotherapeutic adjunct for autism spectrum disorders (ASD).
authors.affiliation: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh 160 014 India.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Bhandari
authors.affiliation: 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.
authors.forename: Anurag
authors.initials: A
authors.lastname: Kuhad
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000523:psychology; D000067877:Autism Spectrum Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D002421:Caudate Nucleus; D002491:Central Nervous System Agents / Q000627:therapeutic use*; D003474:Curcumin / Q000627:therapeutic use*; D007276:Injections, Intraventricular; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D011699:Putamen; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects
chemical_list: D002491:Central Nervous System Agents; D011422:Propionates; D011619:Psychotropic Drugs; D003474:Curcumin
keywords: Autism spectrum disorder (ASD); Curcumin; MMP-9; Neurobehavioural; Oxido-nitrosative stress; TNF-α