Brain's DNA Repair Response to Neurotoxicants
Abstract
Parkinson's Disease (PD) is associated with death of dopaminergic (DA) neurons in the substantia nigra (SN) of the brain. Military personnel abroad are at a greater risk of exposure to pesticides and toxins which may selectively damage DA neurons in the SN and increase the probability of development of Parkinson's disease (PD) later in life. The toxins of interest are mitochondrial poisons that create a bioenergetic crisis and generate toxic oxyradicals which damage macromolecules, including DNA. We hypothesize that regulation of the DNA repair response within certain neurons of the SN (the pars compacta) may be a critical determinant for their vulnerability to these neurotoxicants. We have measured regional differences in the brain's capacity to increase repair of oxidized DNA (indicated by oxyguanosine glycosylase (OGG1) activity) to three distinct chemical classes of neurotoxins (MPTP, two mycotoxins, and an organochloriine pesticide). At the end of the second year of the project, we have found that the temporal and spatial profile of OGG1 activity across brain regions elicted by each class of neurotoxicant is distinct and unique. Although all three toxicants cause DA depletion in striatum, only MPTP caused loss of DA neurons in midbrain. However, it is possible that superimposition of age-related loss of DA neurons over the moderate DS depletion caused by OTA may result in early onset parkinsonism.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA452374
Entities
People
- Juan Sanchez-ramos
Organizations
- University of Tampa