title: Genetic correlational analysis reveals no association between MPP+ and the severity of striatal dopaminergic damage following MPTP treatment in BXD mouse strains.
abstract: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a pro-neurotoxicant that must be metabolized to 1-methyl-4-phenylpyridinium (MPP(+)) and taken up into striatal dopaminergic neurons to produce neurodegeneration. Recently, we showed wide genetic variability in MPTP-associated neuronal damage in a panel of recombinant inbred mouse strains. Here we examined the amount of MPP(+) produced in the striatum in the same strains of inbred BXD mice. This allowed us to determine if the differences in the dopaminergic neurotoxicity and associated astrogliosis among the BXD mouse strains were due to differential metabolism of MPTP to MPP(+). Using the same BXD mouse strains examined previously (Jones et al., 2013) we found that the extent of the striatal damage produced following MPTP treatment is not correlated quantitatively with the production of MPP(+) in the striatum. Our findings also extend those of others regarding strain differences in MPTP-induced dopaminergic neurotoxicity. Importantly, our finding suggests that additional factors influence the neurodegenerative response other than the presence and amount of the toxicant at the target site.
authors.affiliation: Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Byron C
authors.initials: BC
authors.lastname: Jones
authors.affiliation: Centers for Disease Control and Prevention-National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: O'Callaghan
authors.affiliation: University of Tennessee Health Sciences Center, Memphis, TN, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: University of Tennessee Health Sciences Center, Memphis, TN, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.affiliation: Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Gelareh
authors.initials: G
authors.lastname: Alam
authors.affiliation: Centers for Disease Control and Prevention-National Institute for Occupational Safety and Health, Morgantown, WV, USA. Electronic address: dum6@cdc.gov.
authors.forename: Diane B
authors.initials: DB
authors.lastname: Miller
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D005911:Gliosis / Q000378:metabolism; D020267:MPTP Poisoning / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D004298:Dopamine
keywords: BXD recombinant inbred mice; Genetic correlational analysis