MRNA and miRNA Expression Analysis in Multiple Brain Regions Following Soman Exposure in Rats

Abstract

Acute and chronic effects of exposure to the potent organophosphate acetylcholinesterase inhibitor soman are an increasing concern for military and civilian populations. High dose exposure results in increased levels of acetylcholine and cholinergic crisis. This cholinergic crisis induces convulsions and seizures and can result in death if left untreated. Some individuals do not experience seizures on high dose exposure although they experience long‐term neurological injury. Understanding the downstream effects of soman at the molecular level is vital to developing a methods for prognosis and treatment and for explaining inter‐individual differences in response. We performed an integrated analysis of miRNA and mRNA expression in brain regions associated with soman exposure and resultant seizure activity in rats. Adult male Sprague‐Dawley rats were exposed subcutaneously to soman. Samples from seizing and non‐seizing animals were collected from the heart, kidney, liver, lungs, spleen, and brain, including the amygdala, hippocampus, hypothalamus, piriform, medial prefrontal cortex, parietal cortex, and thalamus at 72 hrs and 90 days following exposure. Initial data from the piriform cortex demonstrates significant differences in expression patterns between animals that seized and those that did not. The observed miRNA expression differences across brain tissue types indicate the hypothalamus has a distinct response from other regions. Functional annotation analysis of miRNA‐mRNA interaction pairs identified many that are likely to be involved in the seizing response.Ongoing work will fully characterize the gene networks and pathways altered by soman exposure and associated with soman‐induced seizure responses across different brain regions and should lead to useful assays for diagnosis, prognosis, or exposure surveillance.Disclaimers:Research was conducted in compliance with the Animal Welfare Act, and all other Federal requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.Support or Funding InformationSupport was provided by interagency agreements between BARDA, the Geneva Foundation (ARO agreement no. W911NF‐13‐1‐0376), and the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) as well as a memorandum of agreement between USAMRICD and the U.S. Army Center of Environmental Health (USACEHR).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.