Accession Number : AD1003983

Title :   Organophosphate Related Alterations in Myelin and Axonal Transport in the Living Mammalian Brain

Descriptive Note : Technical Report,30 Sep 2014,29 Sep 2015

Corporate Author : Georgia Health Sciences University Augusta United States

Personal Author(s) : Terry,Alvin V

Full Text :

Report Date : 01 Oct 2015

Pagination or Media Count : 18

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.


Distribution Statement : APPROVED FOR PUBLIC RELEASE