A Murine Model of Genetic and Environmental Neurotoxicant Action

Abstract

This project studies interactions between genes, the environment, and age in causing mouse Parkinsonism. We use mice overexpressing wild-type or a doubly mutated form of human a-synuclein (ha-SYN). We created and characterized these two constructs on a DNA, RNA, and protein levels. Both the wild-type and doubly mutated lines express functional ha-SYN in dopaminergic terminals. The doubly-mutated ha-SYN line declines in locomotor behavior, levels of dopamine (DA) and metabolites, and number of TH+ neurons in the substantia nigra pars compacta throughout its life-span. These changes resemble those seen in human Parkinsonism. This line also fails to respond to a presynaptic dose of apomorphine, but is supersensitive to a higher postsynaptic dose of apomorphine consistent with denervation supersensitivity. We demonstrate age and gender specific effects of combined neurotoxicants. We report a plausible mechanism for the potentiation of both MPTP and paraquat toxicity by selective dithiocarbamates.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2002
Accession Number
ADA416202

Entities

People

  • Eric K. Richfield

Organizations

  • University of Rochester

Tags

DTIC Thesaurus Topics

  • Amines
  • Blood-Brain Barrier
  • Brain
  • Cells
  • Cellular Structures
  • Central Nervous System
  • Chemistry
  • Environmental Health
  • Genetics
  • Liquid Chromatography
  • Nervous System
  • Neurodegeneration
  • Neurons
  • Neurosciences
  • Parkinson'S Disease
  • Two Dimensional

Fields of Study

  • Biology

Readers

  • Molecular and Cellular Biology
  • Neurodegenerative Parkinson's Disease and Rickettsial Disease handbook, including the data level of dopamine, BC, neurons, and PD.
  • Neuroscience

Technology Areas

  • Biotechnology