Global changes in the expression patterns of RNA isolated from the hippocampus and cortex of VX exposed mice.
One of the established activities of the nerve agent VX is inhibition of the enzyme acetylcholinesterase (AChE). This inhibition affects the cholinergic nervous system by decreasing the activity of the neurotransmitter-hydrolyzing enzyme cholinesterase (ChE). In an effort to gain a more comprehensive understanding of the molecular pathways affected by low-level exposure to VX, an expression profiling approach was used to identify genes with altered RNA expression patterns after exposure.Specifically, mice were exposed to 0.1, 0.2, 0.4, and 0.6 LD50 VX for a period of 2 weeks. At 2 h, 72 h, and 2 weeks after the final exposure, RNA was isolated from both the hippocampus and the cortex. Changes in gene expression levels were assessed by DNA microarray technology and grouped according to their expression patterns. Data presented here demonstrate that 2 weeks postexposure all up-regulated gene expression has returned to pre-exposure levels, including genes related to the central nervous system. Additionally, this investigation has revealed non-AChE pathway genes involved in other neuronal functions that display altered expression profiles after VX exposure.
Blanton
Jason L
JL
United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5400, USA.
D'Ambrozio
Jonathan A
JA
Sistrunk
James E
JE
Midboe
Eric G
EG
D000110:Acetylcholinesterase / Q000097:blood / Q000187:drug effects; D000818:Animals; D002091:Butyrylcholinesterase / Q000097:blood / Q000187:drug effects; D002540:Cerebral Cortex / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000737:chemistry*; D007279:Injections, Subcutaneous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage / Q000633:toxicity*; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002800:Cholinesterase Inhibitors; D009946:Organothiophosphorus Compounds; D012313:RNA; C009680:VX-agent