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

Details

• Alternative Title:
  Neurotoxicol Teratol
• Personal Author:
  Jones, Byron C. ; O’Callaghan, James P. ; Lu, Lu ; Williams, Robert W. ; Alam, Gelareh ; Miller, Diane B.
• Description:
  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.
• Subjects:
  Animals Article BXD Recombinant Inbred Mice Dopamine Genetic Correlational Analysis Gliosis Male Mice Mice, Inbred Strains MPTP Poisoning Neostriatum Species Specificity

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• Source:
  Neurotoxicol Teratol. 45:91-92
• Pubmed ID:
  25192776
• Pubmed Central ID:
  PMC7401901
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHS/United States ; R01 ES022614/ES/NIEHS NIH HHS/United States ; U01AA016662/AA/NIAAA NIH HHS/United States ; U01 AA013499/AA/NIAAA NIH HHS/United States
• Volume:
  45
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:0526a0fc9ff7765ea9f8f609090650234541fe039fca6357a352ea9c7d623a33
• Download URL:
  https://stacks.cdc.gov/view/cdc/91512/cdc_91512_DS1.pdf
• File Type:
  [PDF - 45.57 KB ]