title: Nigrostriatal neuronal death following chronic dichlorvos exposure: crosstalk between mitochondrial impairments, α synuclein aggregation, oxidative damage and behavioral changes.
abstract: BACKGROUND
  In recent years, several lines of evidence have shown an increase in Parkinson's disease prevalence in rural environments where pesticides are heavily used. Although, the underlying mechanism for neuronal degeneration in sporadic PD remains unknown, mitochondrial dysfunction, oxidative stress and proteasomal dysfunction are proposed as contributing factors. In this study rats were chronically and continuously exposed to the pesticide, dichlorvos to identify the molecular mechanism of nigrostaital neuronal degeneration.
  
  
  RESULTS
  Chronic dichlorvos exposure (2.50 mg/kg b.wt.s.c/daily for 12 weeks) caused nigrostriatal dopaminergic degeneration. The degenerative changes were accompanied by a loss of 60-80% of the nigral dopamine neurons and 60-70% reduction in striatal dopamine and tyrosine hydroxylase levels. Dichlorvos exposed animals also showed α -synuclein and ubiquitin positive inclusions along with swollen, dystrophic neurites and mitochondrial abnormalities like decreased complex I&IV activities, increased mitochondrial size, axonal degeneration and presence of electron dense perinuclear cytoplasmic inclusions in the substantia nigra of rats. These animals also showed evidence of oxidative stress, including increased mitochondrial ROS levels, decreased MnSOD activity and increased lipid peroxidation. Measurable impairments in neurobehavioral indices were also observed. Notable exacerbations in motor impairments, open field and catalepsy were also evident in dichlorvos exposed animals.
  
  
  CONCLUSIONS
  All these findings taken together indicate that chronic dichlorvos exposure may cause nigrostaital neurodegenaration and significant behavioral impairments.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: B K
authors.initials: BK
authors.lastname: Binukumar
authors.forename: Amanjit
authors.initials: A
authors.lastname: Bal
authors.forename: Ramesh J L
authors.initials: RJ
authors.lastname: Kandimalla
authors.forename: Kiran Dip
authors.initials: KD
authors.lastname: Gill
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D004006:Dichlorvos / Q000494:pharmacology*; D006801:Humans; D007306:Insecticides / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D009483:Neuropsychological Tests; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D025801:Ubiquitin / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D007306:Insecticides; D025801:Ubiquitin; D051844:alpha-Synuclein; D004006:Dichlorvos