Dataset Information

Quantitative T₂ MRI is predictive of neurodegeneration following organophosphate exposure in a rat model.

ABSTRACT: Organophosphorus compounds, such as chemical warfare nerve agents and pesticides, are known to cause neurological damage. This study measured nerve agent-related neuropathology and determined whether quantitative T₂ MRI could be used as a biomarker of neurodegeneration. Quantitative T₂ MRI was performed using a 9.4 T MRI on rats prior to and following soman exposure. T₂ images were taken at least 24 h prior, 1 h and 18-24 h after soman exposure. Rats were pre- and post-treated with HI-6 dimethanesulfonate and atropine methyl nitrate. A multicomponent T₂ acquisition and analysis was performed. Brains were stained with Fluoro-Jade C to assess neurodegeneration. Rats exposed to soman developed behavioral expression of electrographic seizures. At 18-24 h after soman exposure, significant increases in T₂, a possible marker of edema, were found in multiple regions. The largest changes were in the piriform cortex (before: 47.7 ± 1.4 ms; 18-24 h: 82.3 ± 13.4 ms). Fluoro-Jade C staining showed significant neurodegeneration 18-24 h post exposure. The piriform cortex had the strongest correlation between the change in relaxation rate and percent neurodegeneration (r?=?0.96, p?2 relaxivity and histopathology supports the use of T₂ as a marker of injury.

SUBMITTER: Lee K

PROVIDER: S-EPMC7400670 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Quantitative T2 MRI is predictive of neurodegeneration following organophosphate exposure in a rat model.

Lee Kevin K Bohnert Sara S Bouchard Matthew M Vair Cory C Farrell Jordan S JS Teskey G Campbell GC Mikler John J Dunn Jeff F JF

Scientific reports 20200803 1

Organophosphorus compounds, such as chemical warfare nerve agents and pesticides, are known to cause neurological damage. This study measured nerve agent-related neuropathology and determined whether quantitative T2 MRI could be used as a biomarker of neurodegeneration. Quantitative T2 MRI was performed using a 9.4 T MRI on rats prior to and following soman exposure. T2 images were taken at least 24 h prior, 1 h and 18-24 h after soman exposure. Rats were pre- an ...[more]

PMID: 32747689

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Project description:Toxicogenomics is a critical area of inquiry for hazard identification and to identify both mechanisms of action and potential markers of exposure to toxic compounds. However, data generated by these experiments are highly dimensional and present challenges to standard statistical approaches, requiring strict correction for multiple comparisons. This stringency often fails to detect meaningful changes to low expression genes and/or eliminate genes with small but consistent changes particularly in tissues where slight changes in expression can have important functional differences, such as brain. Machine learning offers an alternative analytical approach for "omics" data that effectively sidesteps the challenges of analyzing highly dimensional data. Using 3 rat RNA transcriptome sets, we utilized an ensemble machine learning approach to predict developmental exposure to a mixture of organophosphate esters (OPEs) in brain (newborn cortex and day 10 hippocampus) and late gestation placenta of male and female rats, and identified genes that informed predictor performance. OPE exposure had sex specific effects on hippocampal transcriptome, and significantly impacted genes associated with mitochondrial transcriptional regulation and cation transport in females, including voltage-gated potassium and calcium channels and subunits. To establish if this holds for other tissues, RNAseq data from cortex and placenta, both previously published and analyzed via a more traditional pipeline, were reanalyzed with the ensemble machine learning methodology. Significant enrichment for pathways of oxidative phosphorylation and electron transport chain was found, suggesting a transcriptomic signature of OPE exposure impacting mitochondrial metabolism across tissue types and developmental epoch. Here we show how machine learning can complement more traditional analytical approaches to identify vulnerable "signature" pathways disrupted by chemical exposures and biomarkers of exposure.

Dataset Information

Quantitative T₂ MRI is predictive of neurodegeneration following organophosphate exposure in a rat model.

Publications

Quantitative T<sub>2</sub> MRI is predictive of neurodegeneration following organophosphate exposure in a rat model.

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