Consequences of developmental exposure to concentrated ambient ultrafine particle air pollution combined with the adult paraquat and maneb model of the Parkinson's disease phenotype in male mice.
Current evidence suggests suceptibility of both the substantia nigra and striatum to exposure to components of air pollution. Further, air pollution has been associated with increased risk of PD diagnsosis in humans or PD-like pathology in animals. This study examined whether exposure of mice to concentrated ambient ultrafine particles (CAPS; <100nm diameter) during the first two weeks of life would alter susceptibility to induction of the Parkinson's disease phenyotype (PDP) in a pesticide-based paraquat and maneb (PQ+MB) model during adulthood utilizing i.p. injections of 10mg/kg PQ and 30mg/kg MB 2× per week for 6 weeks. Evidence of CAPS-induced enhancement of the PQ+MB PDP was limited primarily to delayed recovery of locomotor activity 24 post-injection of PQ+MB that could be related to alterations in striatal GABA inhibitory function. Absence of more extensive interactions might also reflect the finding that CAPS and PQ+MB appeared to differentially target the nigrostriatal dopamine and amino acid systems, with CAPS impacting striatum and PQ+MB impacting dopamine-glutamate function in midbrain; both CAPS and PQ+MB elevated glutamate levels in these specific regions, consistent with potential excitotoxicity. These findings demonstrate the ability of postnatal CAPS to produce locomotor dysfunction and dopaminergic and glutamateric changes, independent of PQ+MB, in brain regions involved in the PDP.
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA. Electronic address: joshua_allen@urmc.rochester.edu.
Joshua L
JL
Allen
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA. Electronic address: suexfliu@hotmail.com.
Xiufang
X
Liu
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA. Electronic address: douglas_weston@urmc.rochester.edu.
Douglas
D
Weston
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA. Electronic address: Katherine_bachmann@urmc.rochester.edu.
Katherine
K
Conrad
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA. Electronic address: gunter_oberdorster@urmc.rochester.edu.
Günter
G
Oberdörster
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA. Electronic address: deborah_cory-slechta@urmc.rochester.edu.
Deborah A
DA
Cory-Slechta
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D008344:Maneb / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D053758:Nanoparticles / Q000633:toxicity; D010269:Paraquat / Q000633:toxicity*; D010300:Parkinson Disease / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D052638:Particulate Matter; D012828:Silicones / Q000633:toxicity; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000393:Air Pollutants; D004338:Drug Combinations; D005659:Fungicides, Industrial; D006540:Herbicides; D052638:Particulate Matter; D012828:Silicones; D008344:Maneb; D014446:Tyrosine 3-Monooxygenase; D010269:Paraquat
Parkinson's disease; Pesticides; Ultrafine Particles