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

Authors
Jones-BC; O'Callaghan-JP; Lu-L; Williams-RW; Alam-G; Miller-DB
Source
Neurotoxicol Teratol 2014 Sep-Oct; 45:91-92
NIOSHTIC No.
20045160
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.
Keywords
Neurotoxins; Methyl-compounds; Laboratory-animals; Laboratory-testing; Chemical-structure; Neurological-reactions; Neurological-system; Neurotoxicity; Metabolism; Genetic-factors; Brain-damage; Brain-function; Brain-matter; Author Keywords: Genetic correlational analysis; BXD recombinant inbred mice
Contact
Diane B. Miller, CDC-NIOSH, Morgantown, WV 26505-2888, USA
CODEN
NETEEC
CAS No.
28289-54-5; 51-61-6
Publication Date
20140901
Document Type
Journal Article
Email Address
dum6@cdc.gov
Fiscal Year
2014
NTIS Accession No.
NTIS Price
Identifying No.
M102014
ISSN
0892-0362
NIOSH Division
HELD
Source Name
Neurotoxicology and Teratology
State
PA; WV; TN
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