Dietary Administration of Paraquat for 13 Weeks Does Not Result in a Loss of Dopaminergic Neurons in the Substantia nigra of C57BL/6J Mice

Authors

Daniel J. Minnema
Kim Z. Travis
Charles B. Breckinridge
Nicholas C. Sturgess
Mark Butt
Jeffrey C. Wolf
Dan Zadory
Melissa J. Beck, Cedarville UniversityFollow
James M. Mathews
Merill O. Tisdale
Andrew R. Cook
Philip A. Botham
Lewis L. Smith

Document Type

Article

Publication Date

3-2014

Journal Title

Journal of Regulatory Toxicology and Pharmacology

Volume

68

Issue

2

First Page

250

Last Page

258

DOI

10.1016/j.yrtph.2013.12.010

Abstract

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.

Keywords

Paraquat, C57BL/6J mice, dopamine, substantia nigra, MPTP

Recommended Citation

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.
https://digitalcommons.cedarville.edu/pharmaceutical_sciences_publications/77