Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of rat hippocampus following exposure to the acetylcholinesterase inhibitor soman

ABSTRACT: Soman (O-Pinacolyl methylphosphonofluoridate) is a potent neurotoxicant. Acute exposure to soman causes profound inhibition of the critical enzyme acetylcholinesterase, resulting in excessive levels of the neurotransmitter acetylcholine. Excessive acetylcholine levels cause convulsions, seizures, and respiratory distress. The initial cholinergic crisis can be overcome by rapid anti-cholinergic therapeutic intervention, resulting in increased survival. However, conventional treatments do not protect the brain from seizure-related damage, and thus neurodegeneration of soman-sensitive areas of the brain is a potential post-exposure outcome. We performed gene expression profiling of rat hippocampus following soman exposure to gain greater insight into the molecular pathogenesis of soman-induced neurodegeneration. Experiment Overall Design: Male Sprague-Dawley rats were pretreated with the oxime HI-6 (l-(((4-aminocarbonyl)pyridinio)methoxyl)methyI)-2-((hydroxyimino)methyl)-pyridinium dichloride; 125 mg/kg, ip) 30 min prior to challenge with soman (180 Î¼g/kg, sc; diluted with 0.9% sodium chloride). One minute after soman challenge, animals were treated with atropine methyl nitrate (2.0 mg/kg, im). Vehicle control animals (n=4; 2 euthanized at 1h, 1 euthanized at 12h, and 1 euthanized at 24h) received an equivalent volume of vehicle (0.9% sodium chloride), HI-6 and atropine. NaÃ¯ve animals (n=3) were also included in the study and received no treatments. Hippocampal tissue was harvested 1, 3, 6, 12, 24, 48, 72, 96, and 168h after soman exposure. A sample size of n=3 was used for all time points except 3h (n=6) and 72h (n=4). RNA was extracted from the hippocampal tissue and used to generate oligonucleotide microarray probes for gene expression profiling using Affymetrix Rat 230 2.0 microarrays.

ORGANISM(S): Rattus norvegicus

SUBMITTER: James Dillman

PROVIDER: E-GEOD-13428 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcription profiling of rat hippocampus following exposure to the acetylcholinesterase inhibitor soman

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