Accession Number:

ADA558946

Title:

Transcriptional Responses of The Nerve Agent-Sensitive Brain Regions Amygdala, Hippocampus, Piriform Cortex, Septum, And Thalamus Following Exposure to the Organophosphonate Anticholinesterase Sarin

Descriptive Note:

Journal article

Corporate Author:

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD

Report Date:

2011-01-01

Pagination or Media Count:

1.0

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.

Subject Categories:

  • Toxicology
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE