Accession Number : ADA452374

Title :   Brain's DNA Repair Response to Neurotoxicants

Descriptive Note : Annual rept. 1 Jul 2004-30 Jun 2005

Corporate Author : TAMPA UNIV FL

Personal Author(s) : Sanchez-Ramos, Juan

Full Text :

Report Date : Jul 2005

Pagination or Media Count : 122

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.


Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE