Systems genetics analysis of MPTP neurotoxicity

Details

• Personal Author:
  Alam G ; Jones BC ; Lu L ; Miller DB ; O'Callaghan JP ; Williams RW
• Description:
  Heavy metals, and pesticides herbicides are suspected risk factors for neurological disorders including Parkinson's disease (PD). Nevertheless, their role is not clearcut, as there are inconsistencies in epidemiological and preclinical research. One reason may be related to individual differences in susceptibility, differences that can be traced to the genetic constitution of humans and animals so exposed. Newer epidemiological and animal methods address the role of genes, the environment and their interaction as key. We recently reported on neurotoxicity of 1-methyl- 4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) in male BXD recombinant inbred mice. In the current study, we examined the effect of MPTP neurotoxicity in females from 9 of the same strains of BXD RI mice. The mice received 12.5 mg/kg MPTP s.c. (vs. saline) and 48 h later brains were taken for biochemical analyses. Striatal dopamine (DA) and its metabolites, DOPAC and HVA, and serotonin and its metabolite, 5-HIAAA, were analyzed by HPLC. DA turnover was assessed using DOPAC/DA and HVA/DA ratios. Striatal tyrosine hydroxylase (TH), glial fibrilary acidic protein (GFAP), and iron content in ventral midbrain were quantified. All dopamine measures, as well as TH and GFAP, demonstrated wide, genotype-dependent differences in response to MPTP. Moreover, strong positive correlations were seen between the sexes for DA, TH, and GFAP. This systemic approach to the study of environmental neurotoxicants in genetic reference populations of mice is likely to elucidate genetic factors underlying individual differences in developing neurodegenerative diseases such as PD. [Description provided by NIOSH]
• Subjects:
  Biochemistry Energy Metabolism Environmental Health Environmental Monitoring Epidemiology Genetics Laboratories Nervous System Nervous System Diseases Occupational Health Pyridines Safety Sex Characteristics Toxicology

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• Keywords:
  Analytical-processes Biochemical-analysis Brain-disorders Dose-response Environmental-factors Exposure-assessment Genes Genetic-factors Laboratory-animals Laboratory-testing Metabolites Methyl-compounds Neurological-diseases Neurotoxic-effects Neurotoxicity Neurotoxins Phenyl-compounds Protein-biochemistry Proteins Recombinant-DNA Sex-factors

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 9 ; Pennsylvania ; Tennessee ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20045973
• Citation:
  Toxicologist 2015 Mar; 144(1):328
• CAS Registry Number:
  1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (CAS RN 28289-54-5) ; Dopamine (CAS RN 51-61-6) ; Serotonin (CAS RN 50-67-9)
• Federal Fiscal Year:
  2015
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b0f6865759a540bc60e65757bbcaf82f59fd2427829c0f6332b2971bb8df3fd5a75e72ad720e9e3d8738abda754ad8ae65be333a3014686b3b6379b1da59569f
• Download URL:
  https://stacks.cdc.gov/view/cdc/201177/cdc_201177_DS1.pdf
• File Type:
  [PDF - 218.11 KB ]