PMID- 22240983
OWN - NLM
STAT- MEDLINE
DCOM- 20120716
LR  - 20161125
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 126
IP  - 2
DP  - 2012 Apr
TI  - Repeated exposure to sublethal doses of the organophosphorus compound VX 
      activates BDNF expression in mouse brain.
PG  - 497-505
LID - 10.1093/toxsci/kfr353 [doi]
AB  - 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 x 5 days/week x 2 weeks) to sublethal doses of 
      VX (0.2 LD(50) and 0.4 LD(50)). 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 LD(50) 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.
FAU - Pizarro, Jose M
AU  - Pizarro JM
AD  - U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving 
      Ground, Maryland 21010, USA.
FAU - Chang, Wenling E
AU  - Chang WE
FAU - Bah, Mariama J
AU  - Bah MJ
FAU - Wright, Linnzi K M
AU  - Wright LK
FAU - Saviolakis, George A
AU  - Saviolakis GA
FAU - Alagappan, Arun
AU  - Alagappan A
FAU - Robison, Christopher L
AU  - Robison CL
FAU - Shah, Jinesh D
AU  - Shah JD
FAU - Meyerhoff, James L
AU  - Meyerhoff JL
FAU - Cerasoli, Douglas M
AU  - Cerasoli DM
FAU - Midboe, Eric G
AU  - Midboe EG
FAU - Lumley, Lucille A
AU  - Lumley LA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120112
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chemical Warfare Agents)
RN  - 0 (Organothiophosphorus Compounds)
RN  - 9A4381183B (VX)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Chemical Warfare Agents/*toxicity
MH  - In Situ Hybridization
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Organothiophosphorus Compounds/administration & dosage/*toxicity
EDAT- 2012/01/14 06:00
MHDA- 2012/07/17 06:00
CRDT- 2012/01/14 06:00
PHST- 2012/01/14 06:00 [entrez]
PHST- 2012/01/14 06:00 [pubmed]
PHST- 2012/07/17 06:00 [medline]
AID - kfr353 [pii]
AID - 10.1093/toxsci/kfr353 [doi]
PST - ppublish
SO  - Toxicol Sci. 2012 Apr;126(2):497-505. doi: 10.1093/toxsci/kfr353. Epub 2012 Jan 
      12.