Accession Number : ADA561857


Title :   Repeated Exposure to Sublethal Doses of the Organophosphorus Compound VX Activates BDNF Expression in Mouse Brain


Descriptive Note : Journal article


Corporate Author : ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD


Personal Author(s) : Pizarro, Jose M ; Chang, Wenling E ; Bah, Mariama J ; Wright, Linnzi K ; Saviolakis, George A ; Alagappan, Arun ; Robison, Christopher L ; Shah, Jinesh D ; Meyerhoff, James L ; Cerasoli, Douglas M


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a561857.pdf


Report Date : Jan 2012


Pagination or Media Count : 10


Abstract : The highly toxic organophosphorus compound VX [O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonate] is an irreversible inhibitor of the enzyme acetylcholinesterase (AChE). Prolonged inhibition of AChE increases endogenous levels of acetylcholine and is toxic at nerve synapses and neuromuscular junctions. We hypothesized that repeated exposure to sublethal doses of VX would affect genes associated with cell survival, neuronal plasticity, and neuronal remodeling, including brain-derived neurotrophic factor (BDNF). We examined the time course of BDNF expression in C57BL/6 mouse brain following repeated exposure (1/day 3 5 days/ week 3 2 weeks) to sublethal doses of VX (0.2 LD50 and 0.4 LD50). BDNF messenger RNA expression was significantly (p 0.05) elevated in multiple brain regions, including the dentate gyrus, CA3, and CA1 regions of the hippocampal formation, as well as the piriform cortex, hypothalamus, amygdala, and thalamus, 72 h after the last 0.4 LD50 VX exposure. BDNF protein expression, however, was only increased in the CA3 region of the hippocampus. Whether increased BDNF in response to sublethal doses of VX exposure is an adaptive response to prevent cellular damage or a precursor to impending brain damage remains to be determined. If elevated BDNF is an adaptive response, exogenous BDNF may be a potential therapeutic target to reduce the toxic effects of nerve agent exposure. Key Words: neurotrophins; BDNF; organophosphorus compounds; chemical warfare nerve agents; VX; mice.


Descriptors :   *ACETYLCHOLINESTERASE , *ORGANOPHOSPHATES , *TOXICITY , *VX AGENT , BRAIN , BRAIN DAMAGE , CELLS(BIOLOGY) , CHEMICAL WARFARE AGENTS , EXPOSURE(PHYSIOLOGY) , NERVE AGENTS , NERVE CELLS , ORGANIC PHOSPHORUS COMPOUNDS , PLASTIC PROPERTIES , RIBONUCLEIC ACIDS , SUBLETHAL DOSAGE , SURVIVABILITY , SYNAPSE


Subject Categories : Biochemistry
      Chemical, Biological and Radiological Warfare


Distribution Statement : APPROVED FOR PUBLIC RELEASE