Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss

The herbicide paraquat, bearing structural similarity to the known dopamine rgic neurotoxicant MPTP, has been suggested as a potential etiologic factor in Parkinson's disease. Consideration of paraquat as a candidate neurotoxi cant requires demonstration that systemic delivery produces substantia nigr a dopaminergic neuron loss and the attendant neurobehavioral syndrome refle cting depletion of dopamine terminals within the striatum. To address these issues paraquat was administered systemically into adult C57 b1/6 mice, am bulatory behavior monitored, substantia nigra dopamine neuron number and st riatal dopamine terminal density quantified. The data indicate that paraqua t like MPTP elicits a dose-dependent decrease in substantia nigra dopaminer gic neurons assessed by a Fluoro-gold prelabeling method, a decline in stri atal dopamine nerve terminal density assessed by measurement of tyrosine hy droxylase immunoreactivity; and neurobehavioral syndrome characterized by r educed ambulatory activity. Taken together, these data suggest that systemi cally absorbed paraquat crosses the blood-brain barrier to cause destructio n of dopamine neurons in the substantia nigra, consequent reduction of dopa minergic innervation of the striatum and a neurobehavioral syndrome similar to the well characterized and bona fide dopaminergic toxin MPTP. (C) 1999 Elsevier Science B.V. All rights reserved.