Low-level inhalation exposure to chemical nerve agent vapor induces expression of neuronal apoptosis and regeneration genes

For over a decade following the end of the first Gulf War in 1991, there has been increasing concern to understand the immediate and persistent effects of sub-acute and low-level exposures to chemical warfare agents. Although low-level exposures may not cause obvious pathology at the time of exposure, they may cause molecular-level alterations in the brain and other vital organ systems. The work described in this manuscript was designed to measure the gene and protein expression alterations in the brains of male and female rats exposed to sub- and peri-miotic levels of the aerosolized nerve agents satin (GB) and cyclosarin (GF). Gene expression was assessed using DNA microarray analysis. The microarray data were verified by real-time RT-PCR and Western immunoblotting where possible. The overall aim of this project is to measure and characterize the gene and protein level alterations that may reveal near term, operational risks as well as changes that may predispose an individual to injury or disease later in life. To date, our results indicate that: 1) low-level inhalation exposure to GB and GF results in the differential expression of a number of neuronal genes, including a group that participate in cellular processes critical to neurological injury and regeneration and 2) there are significant gender-associated differences in the level and type of gene expression response.