title: Dietary administration of diquat for 13 weeks does not result in a loss of dopaminergic neurons in the substantia nigra of C57BL/6J mice.
abstract: Male and female C57BL/6J mice were administered diquat dibromide (DQ∙Br2) in their diets at concentrations of 0 (control), 12.5 and 62.5 ppm for 13 weeks to assess the potential effects of DQ on the nigrostriatal dopaminergic system. Achieved dose levels at 62.5 ppm were 6.4 and 7.6 mg DQ (ion)/kg bw/day for males and females, respectively. A separate group of mice was administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) ip as a positive control. The comparative effects of DQ and MPTP on the substantia nigra pars compacta (SNpc) and/or striatum were assessed using neurochemical, neuropathological and stereological endpoints. Morphological and stereological assessments were performed by investigators who were "blinded" to dose group. DQ had no effect on striatal dopamine concentration or dopamine turnover. There was no evidence of neuronal degeneration, astrocytic or microglial activation, or a reduction in the number of tyrosine hydroxylase positive (TH(+)) neurons in the SNpc or neuronal processes in the striatum of DQ-treated mice. These results are consistent with the rapid clearance of DQ from the brain following a single dose of radiolabeled DQ. In contrast, MPTP-treated mice exhibited decreased striatal dopamine concentration, reduced numbers of TH(+) neurons in the SNpc, and neuropathological changes, including neuronal necrosis, as well as astrocytic and microglial activation in the striatum and SNpc.
authors.affiliation: Syngenta Crop Protection, LLC, P.O. Box 18300, Greensboro, NC, 27419-8300, USA. Electronic address: daniel.minnema@syngenta.com.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Minnema
authors.affiliation: Syngenta Limited, Jealott's Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK. Electronic address: kim.travis@syngenta.com.
authors.forename: Kim Z
authors.initials: KZ
authors.lastname: Travis
authors.affiliation: Syngenta Crop Protection, LLC, P.O. Box 18300, Greensboro, NC, 27419-8300, USA. Electronic address: charles.breckenridge@syngenta.com.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Breckenridge
authors.affiliation: Syngenta Limited, Jealott's Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK. Electronic address: nick.sturgess@syngenta.com.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Sturgess
authors.affiliation: Tox Path Specialists, LLC, 8420 Gas House Pike, Frederick, MD, 21701-2607, USA. Electronic address: mbutt@toxpath.net.
authors.forename: Mark
authors.initials: M
authors.lastname: Butt
authors.affiliation: Experimental Pathology Laboratories, Inc., 45600 Terminal Drive, Sterling, VA, 20166, USA. Electronic address: jwolf@epl-Inc.com.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wolf
authors.affiliation: Experimental Pathology Laboratories, Inc., 45600 Terminal Drive, Sterling, VA, 20166, USA. Electronic address: dzadory@epl-Inc.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Zadory
authors.affiliation: WIL Research, Ashland, OH, 44805, USA. Electronic address: mark.herberth@wilresearch.com.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Herberth
authors.affiliation: RTI International, 3040 Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA. Electronic address: slwatson@rti.org.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Watson
authors.affiliation: Syngenta Limited, Jealott's Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK. Electronic address: andy.cook@syngenta.com.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Cook
authors.affiliation: Syngenta Limited, Jealott's Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK. Electronic address: phil.botham@syngenta.com.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Botham
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004032:Diet; D004178:Diquat / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects; D005260:Female; D006540:Herbicides / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D059550:Toxicity Tests, Subchronic
chemical_list: D006540:Herbicides; D015102:3,4-Dihydroxyphenylacetic Acid; D004178:Diquat; D004298:Dopamine; D006719:Homovanillic Acid
keywords: C57BL/6J mice; Diquat; Dopamine; MPTP; Substantia nigra