title: Caffeine protects against combined paraquat and maneb-induced dopaminergic neuron degeneration.
abstract: Environmental exposures suspected of contributing to the pathophysiology of Parkinson's disease (PD) include potentially neurotoxic pesticides, which have been linked to an increased risk of PD. Conversely, possible protective factors such as the adenosine antagonist caffeine have been linked to a reduced risk of the disease. Here we assessed whether caffeine alters dopaminergic neuron loss induced by exposure to environmentally relevant pesticides (paraquat and maneb) over 8weeks. The number of nigral neurons positive for tyrosine hydroxylase immunoreactivity (TH+) was assessed using stereological methods and found to be significantly reduced (to 60% of control) by combined pesticide treatment. Caffeine at 20mg/kg significantly reduced TH+ neuron loss (to 85% of the respective control). The results demonstrate the neuroprotective potential of caffeine in a chronic pesticide exposure model of model of PD.
authors.affiliation: MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Kachroo
authors.forename: Michael C
authors.initials: MC
authors.lastname: Irizarry
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schwarzschild
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002452:Cell Count; D002908:Chronic Disease; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D005659:Fungicides, Industrial / Q000037:antagonists & inhibitors / Q000633:toxicity; D006540:Herbicides / Q000037:antagonists & inhibitors / Q000633:toxicity; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008344:Maneb / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000633:toxicity*; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology
chemical_list: D005659:Fungicides, Industrial; D006540:Herbicides; D018696:Neuroprotective Agents; D008344:Maneb; D002110:Caffeine; D010269:Paraquat; D004298:Dopamine