title: Viral-toxin interactions and Parkinson's disease: poly I:C priming enhanced the neurodegenerative effects of paraquat.
abstract: BACKGROUND
  Parkinson's disease (PD) has been linked with exposure to a variety of environmental and immunological insults (for example, infectious pathogens) in which inflammatory and oxidative processes seem to be involved. In particular, epidemiological studies have found that pesticide exposure and infections may be linked with the incidence of PD. The present study sought to determine whether exposure to a viral mimic prior to exposure to pesticides would exacerbate PD-like pathology.
  
  
  METHODS
  Mice received a supra-nigral infusion of 5 μg of the double-stranded RNA viral analog, polyinosinic: polycytidylic acid (poly(I:C)), followed 2, 7 or 14 days later by administration of the pesticide, paraquat (nine 10 mg/kg injections over three weeks).
  
  
  RESULTS
  As hypothesized, poly(I:C) pre-treatment enhanced dopamine (DA) neuron loss in the substantia nigra pars compacta elicited by subsequent paraquat treatment. The augmented neuronal loss was accompanied by robust signs of microglial activation, and by increased expression of the catalytic subunit (gp91) of the NADPH oxidase oxidative stress enzyme. However, the paraquat and poly(I:C) treatments did not appreciably affect home-cage activity, striatal DA terminals, or subventricular neurogenesis.
  
  
  CONCLUSIONS
  These findings suggest that viral agents can sensitize microglial-dependent inflammatory responses, thereby rendering nigral DA neurons vulnerable to further environmental toxin exposure.
authors.affiliation: Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bobyn
authors.forename: Emily N
authors.initials: EN
authors.lastname: Mangano
authors.forename: Anusha
authors.initials: A
authors.lastname: Gandhi
authors.forename: Eric
authors.initials: E
authors.lastname: Nelson
authors.forename: Kerry
authors.initials: K
authors.lastname: Moloney
authors.forename: Melanie
authors.initials: M
authors.lastname: Clarke
authors.forename: Shawn
authors.initials: S
authors.lastname: Hayley
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004357:Drug Synergism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D010269:Paraquat / Q000378:metabolism / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D011070:Poly I-C / Q000378:metabolism / Q000633:toxicity*
chemical_list: D000998:Antiviral Agents; D011070:Poly I-C; D010269:Paraquat