Environmental and Occupational Health Sciences Institute

Toxicology Division

Neurotoxicology


  • Evaluation of oxidative stress mechanisms of the combined paraquat + maneb exposure model of the Parkinson's disease phenotype.

 

  • A pesticide based developmental model of Parkinson's disease, postnatal paraquat + maneb, produces significant elevation in lipid peroxidation levels even 6 months post exposure, suggesting ongoing elevation in oxidative stress state. 

 

  • Development of a double-mutant alpha-synuclein transgenic model of the Parkinson's Disease phenotype that enhances vulnerability to the pesticides paraquat and maneb in a gene-environment interaction model.

 

  • Laser capture microdissection of nigral dopaminergic neurons from postnatal saline and paraquat + maneb exposed mice for microarray analysis to determine gene-related changes associated with these early exposures.

 

  • Exploration of gender associated differences and their role in neuroprotection following exposure to paraquat and maneb, given the apparent protection of females.

 

  • Determination of mechanism of enhanced vulnerability to paraquat following prenatal exposure to maneb.

 

  • The neurotransmitter dopamine contributes to the degeneration of the nigral dopaminergic neurons following exposure to mitochondrial poisons.

 

  • The toxicity of manganese to dopaminergic neurons differs from that produced by mitochondrial poisons.

 

  • Adenosine A2a antagonists protect against toxicity produced by intrastriatal mitochondrial impairment via receptors located outside of the striatum.

 

  • Established a chronic in vitro model of mitochondrial dysfunction to study cellular mechanisms underlying degeneration of dopamine neurons as may occur in neurodegenerative diseases such as Parkinson's disease.

 

  • Showed that dopamine could inhibit respiration by both monoamine oxidase-dependent and independent mechanisms.

 

  • Demonstrated that oxidative stress increased glutaredoxin catalyzed glutathione-protein-mixed disulfide formation in mesencephalic neurons and that this correlated with neuroprotection.

 

  • First to demonstrate functional glutaredoxin activity in brain mitochondria.

 

  • Demonstrated that intracellular glutathione could be elevated in neurons with glutathione-ethyl ester treatment and that this protected cells against oxidative stress or mitochondrial dysfunction.

 

  • Perinatal exposure of mice to lead reduces striatal dopamine content in adult female offspring.

 

  • Demonstration of significant interactions between Pb exposure and environmental stress that result in permanently altered stress responsivity of offspring.

 

  • Documented permanent changes in corticosterone levels and HPA axis function in response to maternal only exposures to Pb with lifetime consequences for offspring.

 

  • Studies on the neurotoxicity of atrazine and its ability to kill dopaminergic neurons.

 

  • Role of environmental metal exposures in autism

 

  • Neuroprotective mechanisms of estradiol against oxidative stress includes the induction of antioxidant enzymes.

 

  • Studies on the role of free radicals in mediating paraquat-induced toxicity in lung and brain tissue

 

  • Studies using in vivo gene delivery with regulatable lentivirus for assessment of dopamine-mediated behaviors with a long-term plan of altering sensitivity to toxicants.

 

  • Ongoing studies using nanofiber matrix to enhance dopamine neurite outgrowth in culture with a long-term plan of enhancing stem cell growth and survival in vivo.