Genetic correlational analysis reveals no association between MPP+ and the severity of striatal dopaminergic damage following MPTP treatment in BXD mouse strains

Byron Jones, James P. O'Callaghan, Lu Lu, Robert Williams, Gelareh Alam, Diane B. Miller

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)91-92
Number of pages2
JournalNeurotoxicology and Teratology
Volume45
DOIs
StatePublished - Sep 1 2014

Fingerprint

Corpus Striatum
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Inbred Strains Mice
1-Methyl-4-phenylpyridinium
Dopaminergic Neurons
Metabolism
Neurons

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

@article{a7c3822405f244b387aa037b4b7b589d,
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.",
author = "Byron Jones and O'Callaghan, {James P.} and Lu Lu and Robert Williams and Gelareh Alam and Miller, {Diane B.}",
year = "2014",
month = "9",
day = "1",
doi = "10.1016/j.ntt.2014.08.005",
language = "English (US)",
volume = "45",
pages = "91--92",
journal = "Neurotoxicology and Teratology",
issn = "0892-0362",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Genetic correlational analysis reveals no association between MPP+ and the severity of striatal dopaminergic damage following MPTP treatment in BXD mouse strains

AU - Jones, Byron

AU - O'Callaghan, James P.

AU - Lu, Lu

AU - Williams, Robert

AU - Alam, Gelareh

AU - Miller, Diane B.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84908375203&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908375203&partnerID=8YFLogxK

U2 - 10.1016/j.ntt.2014.08.005

DO - 10.1016/j.ntt.2014.08.005

M3 - Article

VL - 45

SP - 91

EP - 92

JO - Neurotoxicology and Teratology

JF - Neurotoxicology and Teratology

SN - 0892-0362

ER -