Dopaminergic toxicity associated with oral exposure to the herbicide atrazine in juvenile male C57BL/6 mice.
The herbicide atrazine (ATR) is a very commonly used pesticide in the United States. and a major ground water contaminant. It has also been recently implicated as a potential basal ganglia toxicant. In the present study, our objective was to determine the effects of ATR exposure on striatal neurochemistry, on the number of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and, as a reference, in the ventral tegmental area (VTA) of male juvenile C57BL/6 mice. Oral exposure to ATR for 14 days dose-dependently decreased the levels of dopamine (DA) and its metabolites in the striatum for up to a week post-treatment. ATR exposure also time- and dose-dependently decreased the number of tyrosine hydroxylase-positive (TH+) dopaminergic neurons in both SNpc and VTA (with effects being slightly more prominent in SNpc), such that the decreases were most evident at 7 weeks post-cessation of exposure to ATR. Together, these data indicate that, in the juvenile male C57BL/6 mouse, the neurotoxic effects of ATR appear to cause transient neurochemical alterations, whereas the loss of TH+ neurons appears to be persistent, possibly confined to basal ganglia dopaminergic neurons, but not exclusive to the SNpc.
Coban
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Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi 39762-6100, USA.
Filipov
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D000284:Administration, Oral; D000818:Animals; D001280:Atrazine / Q000633:toxicity*; D002452:Cell Count; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006540:Herbicides / Q000633:toxicity*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D006540:Herbicides; D014446:Tyrosine 3-Monooxygenase; D001280:Atrazine; D004298:Dopamine