Dietary Administration of Paraquat for 13 Weeks Does Not Result in a Loss of Dopaminergic Neurons in the Substantia nigra of C57BL/6J Mice
Journal of Regulatory Toxicology and Pharmacology
Several investigations have reported that mice administered paraquat dichloride (PQ·Cl2) by intraperitoneal injection exhibit a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). In this study, male and female C57BL/6J mice were administered PQ·Cl2 in the diet at concentrations of 0 (control), 10, and 50 ppm for a duration of 13 weeks. A separate group of mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) during week 12 as positive controls to produce a loss of dopaminergic neurons in the SNpc. The comparative effects of PQ and MPTP on the SNpc and/or striatum were assessed using neurochemical, neuropathological, and stereological endpoints. Morphological and stereological assessments were performed by investigators ‘blinded’ to the origin of the tissue. Neither dose of PQ·Cl2 (10 or 50 ppm in the diet) caused a loss of striatal dopamine or dopamine metabolite concentrations in the brains of mice. Pathological assessments of the SNpc and striatum showed no evidence of neuronal degeneration or astrocytic/microglial activation. Furthermore, the number of tyrosine hydroxylase-positive (TH+) neurons in the SNpc was not reduced in PQ-treated mice. In contrast, MPTP caused a decrease in striatal dopamine concentration, a reduction in TH+ neurons in the SNpc, and significant pathological changes including astrocytic and microglial activation in the striatum and SNpc. The MPTP-induced effects were greater in males than in females. It is concluded that 13 weeks of continuous dietary exposure of C57BL/6J mice to 50 ppm PQ·Cl2 (equivalent to 10.2 and 15.6 mg PQ ion/kg body weight/day for males and females, respectively) does not result in the loss of, or damage to, dopaminergic neurons in the SNpc.
Paraquat, C57BL/6J mice, dopamine, substantia nigra, MPTP
Minnema, Daniel J.; Travis, Kim Z.; Breckinridge, Charles B.; Sturgess, Nicholas C.; Butt, Mark; Wolf, Jeffrey C.; Zadory, Dan; Beck, Melissa J.; Mathews, James M.; Tisdale, Merill O.; Cook, Andrew R.; Botham, Philip A.; and Smith, Lewis L., "Dietary Administration of Paraquat for 13 Weeks Does Not Result in a Loss of Dopaminergic Neurons in the Substantia nigra of C57BL/6J Mice" (2014). Pharmaceutical Sciences Faculty Publications. 77.