Systemic exposure to paraquat and maneb models early Parkinson's disease in young adult rats.
In recent years, several lines of evidence have shown an increase in Parkinson's disease (PD) prevalence in rural environments where pesticides are widely used. Paraquat (PQ--herbicide) and maneb (MB--fungicide) are among the compounds suspected to induce neuronal degeneration and motor deficits characteristics of PD. Here, we investigated the effects of PQ and MB on dopaminergic (DA) neuron-glia cultures and in vivo in young adult rats. In vitro, PQ led to a loss of DA as compared to non-DA neurons and microglial activation in a dose-dependent manner. Addition of MB had no further effect nor did it lead to microglial activation when used alone. In vivo, 2-month old young adult rats were subjected to intraperitoneal injections of vehicle (n = 4), PQ alone (n = 8), or PQ in combination with MB (n = 8) twice a week for 4 weeks and were sacrificed the day following the last injection. Significant loss of nigral DA neurons was observed in both treatment groups, but a significant decrease in striatal DA fibers was not found. Microglial activation was seen in the nigra of rats subjected to PQ with or without MB. Behavioral analyses demonstrated a mixed pattern of motor impairments, which may have been related to early effects of nigral DA neuronal loss or systemic effects associated with MB exposure in addition to PQ. These results indicate that exposure to PQ with or without MB induces neurodegeneration which might occur via an early inflammatory response in young adult animals.
Cicchetti
Francesca
F
Centre de Recherche en Neurosciences, CHUL, RC-9800, 2705 Boulevard Laurier, Sainte-Foy, QC, Canada G1V 4G2. Francesca.Cicchetti@crchul.ulaval.ca
Lapointe
Nicolas
N
Roberge-Tremblay
Antoine
A
Saint-Pierre
Martine
M
Jimenez
Lincoln
L
Ficke
Brooks W
BW
Gross
Robert E
RE
D017668:Age of Onset; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D005659:Fungicides, Industrial / Q000633:toxicity; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D006540:Herbicides / Q000633:toxicity; D008297:Male; D008344:Maneb / Q000633:toxicity*; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010269:Paraquat / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology
D005659:Fungicides, Industrial; D006540:Herbicides; D008344:Maneb; D010269:Paraquat; D004298:Dopamine