Transcriptional Responses of The Nerve Agent-Sensitive Brain Regions Amygdala, Hippocampus, Piriform Cortex, Septum, And Thalamus Following Exposure to the Organophosphonate Anticholinesterase Sarin
Abstract
To advance our understanding of the molecular mechanisms involved in sarin-induced toxicity, we analyzed gene expression changes in four other areas of the rat brain known to be affected by nerve agent-induced seizure (amygdala, hippocampus, septum, and thalamus). Methods: We compared the transcriptional response of these four brain regions to sarin-induced seizure with the response previously characterized in the piriform cortex. In this study, rats were challenged with 1.0 x LD50 sarin and subsequently treated with atropine sulfate, 2-pyridine aldoxime methlychloride, and diazepam. The four brain regions were collected at 0.25, 1, 3, 6 and 24 h after seizure onset, and total RNA was processed for microarray analysis. Results: Principal component analysis identified brain region and time following seizure onset as a major sources of variability within the dataset. Analysis of variance identified genes significantly changed following sarin-induced seizure, and gene ontology analysis identified biological pathways, functions and networks of genes significantly affected by sarin-induced seizure over the 24-h time course. Many of the molecular functions and pathways identified as being most significant across all of the brain regions were indicative of a inflammatory response. There were also a number of molecular responses that were unique for each brain region, with the thalamus having the most distinct response to nerve agent-induced seizure.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2011
- Accession Number
- ADA558946
Entities
People
- Christoper L. Robison
- James F. Dillman Iii
- James L. Meyerhoff
- Kimberly D. Spradling
- Lucille A. Lumley
Organizations
- United States Army Medical Research Institute of Chemical Defense