Accession Number:

ADA426356

Title:

Molecular Targets for Organophosphates in the Central Nervous System

Descriptive Note:

Annual rept. 18 May 2003-18 May 2004

Corporate Author:

MARYLAND UNIV BALTIMORE

Personal Author(s):

Report Date:

2004-06-01

Pagination or Media Count:

23.0

Abstract:

In a continued effort to determine the actions and effects of low-level exposure to the nerve agents sarin, soman, and VX in the mammalian CNS and to help design countermeasures to treat andor prevent such effects, we have been worked toward accomplishing the following objectives 1. Determine whether pyridostigmine and the nicotinic APL galanthamine also spelled galantamine can antagonize the effects of VX, soman, and sarin on synaptic transmission in the mammalian CNS, and, if so, to elucidate the mechanism. 2. Investigate whether chronic exposure of CNS neurons to soman, VX, and sarin results in neuronal death. a. Determine the mechanisms that contributes to nerve agent-induced cell death apoptosis andor necrosis b. Determine which pathways AKT, MEKMEK Kinase, caspases, etc. underlie nerve-agent-induced neuronal death, in the case apoptosis is the major component of neuronal death induced by chronic exposure to low levels of sarin, soman, and VX. c. Investigate if neuronal death induced by chronic exposure to low levels of sarin, soman, and VX can be antagonized by galantamine d. Analyze the effects of pyridostigmine on neuronal viability and determine if pyridostigmine could antagonize or facilitate neuronal death induced by chronic exposure to low levels of sarin, soman, and VX. 3. Determine the effects of chronic exposure to low levels of sarin, soman, and VX on acetylcholinesterase, choline acetyltransferase, and nicotinic receptor expression in primary cultures of hippocampal neurons. 4. Investigate whether chronic exposure to low levels of sarin, soman, and VX alters KYNA levels in the rat brain.

Subject Categories:

  • Anatomy and Physiology
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE