Organophosphate Related Alterations in Myelin and Axonal Transport in the Living Mammalian Brain
Abstract
The overall goal of this project is to determine the underlying mechanisms for the neurological symptoms associated with Gulf War Illness. The central hypothesis is that subthreshold exposures to organophosphates-OPs (defined as exposures not associated with acute signs of toxicity) may have adversely affected axonal transport and/or myelin integrity in affected individuals. We are studying two OPs, a representative insecticide that was used in the first gulf war, chlorpyrifos (CPF), and a representative, nerve agent, diisopropylfluorophosphate (DFP) in rats. The experiments for Specific Aim #1: are now finished. This aim was designed to evaluate OP effects on axonal transport in the living rat brain using manganese-enhanced magnetic resonance imaging (MEMRI) of the optic nerve axonal projections from the retina to the superior colliculus. The following procedures were conducted (N=6): 1) baseline MRI scans; 2) daily injections of vehicle, chlorpyrifos (3.0-18.0 mg/kg) or DFP (0.125-0.5 mg/kg x 14 days); 2) a second MRI scan on the day following the last drug injection; 3) a third scan after a 4 week (OP-free) washout period. For each animal, a separate 6 hour and 24 hour scan was performed after Mn2+ eye injection. For this work one manuscript (the CPF paper) has been published and it is anticipated that a second manuscript (the DFP-MEMRI paper) will be submitted by the end of this year. The experiments for specific aim #2, devoted to the evaluation of OP-related effects on myelin with diffusion tensor imaging-(DTI) and histology are currently underway. A one-year no-cost extension for this project has been granted to allow for the remaining experiments to be finished.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- AD1003983
Entities
People
- Alvin V. Terry