Prolonged inflammatory gene response following soman-induced seizures in mice

Dhote, Franck; Peinnequin, André; Carpentier, Pierre; Baille, Valérie; Delacour, Claire; Foquin, Annie; Lallement, G.; Dorandeu, Frédéric

doi:10.1016/j.tox.2007.05.032

Cited by 111 publications

(72 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1a). The extensive activation of inflammatory responses in the seizing rats, in particular by neurotoxic and pro-inflammatory cytokines, such as Il-1β, Tnf-α, and Il-6, was observed in all brain regions (Spradling et al, 2011a(Spradling et al, , 2011b, consistent with findings from previous studies (Chapman et al, 2006;Dhote et al, 2007;Dillman et al, 2009;Johnson and Kan, 2010;Svensson et al, 2001Svensson et al, , 2005Williams et al, 2003).…”

Section: Introductionsupporting

confidence: 91%

Neuroprotective mechanisms activated in non-seizing rats exposed to sarin

Spradling-Reeves

Dillman

et al. 2015

Brain Research

View full text Add to dashboard Cite

Exposure to organophosphate (OP) nerve agents, such as sarin, may lead to uncontrolled seizures and irreversible brain injury and neuropathology. In rat studies, a median lethal dose of sarin leads to approximately half of the animals developing seizures. Whereas previous studies analyzed transcriptomic effects associated with seizing sarin-exposed rats, our study focused on the cohort of sarin-exposed rats that did not develop seizures. We analyzed the genomic changes occurring in sarin-exposed, non-seizing rats and compared differentially expressed genes and pathway activation to those of seizing rats. At the earliest time point (0.25 h) and in multiple sarin-sensitive brain regions, defense response genes were commonly expressed in both groups of animals as compared to the control groups. All sarin-exposed animals activated the MAPK signaling pathway, but only the seizing rats activated the apoptotic-associated JNK and p38 MAPK signaling sub-pathway. A unique phenotype of the non-seizing rats was the altered expression levels of genes that generally suppress inflammation or apoptosis. Importantly, the early transcriptional response for inflammation- and apoptosis-related genes in the thalamus showed opposite trends, with significantly down-regulated genes being up-regulated, and vice versa, between the seizing and non-seizing rats. These observations lend support to the hypothesis that regulation of anti-inflammatory genes might be part of an active and sufficient response in the non-seizing group to protect against the onset of seizures. As such, stimulating or activating these responses via pretreatment strategies could boost resilience against nerve agent exposures.

show abstract

Section: Introductionsupporting

confidence: 91%

Neuroprotective mechanisms activated in non-seizing rats exposed to sarin

Spradling-Reeves

Dillman

et al. 2015

Brain Research

View full text Add to dashboard Cite

show abstract

“…A recent, population-based examination that took place as part of the HEAL study in Bangladesh also found no association between arsenic exposure and diabetes. 188 In this study, more than 90% of the 11,319 cohort members were exposed to drinking water with arsenic concentration < 300 μg/L. The adjusted odds ratios for diabetes in relation to quintiles of time-weighted, arsenic concentrations in water were 1.00 for concentrations of 0. study between arsenic exposure and diabetes when urinary concentrations of arsenic were measured instead of those in drinking water.…”

Section: Diabetesmentioning

confidence: 68%

“…189 Additionally, some historical case-control studies link chloramphenicol use to the development of leukemia, which in many cases is diagnosed after aplastic anemia. 188 The risk of leukemia is higher with longer chloramphenicol treatment periods. It is possible that children are more likely to develop leukemia after chloramphenicol use than adults, as the relationship in studies with child subjects is usually stronger than it is in studies on adults.…”

Section: Chloramphenicolmentioning

confidence: 99%

“…It is possible that children are more likely to develop leukemia after chloramphenicol use than adults, as the relationship in studies with child subjects is usually stronger than it is in studies on adults. 188 Chloramphenicol use is also associated with bone-marrow suppression and optic neuritis, 190 191 but these conditions resolve after the antibiotic is withdrawn and are not associated with longterm sequelae.…”

Section: Chloramphenicolmentioning

confidence: 99%

See 1 more Smart Citation

Assessment of Potential Long Term Health Effects on Army Human Test Subjects of Relevant Biological and Chemical Agents, Drugs, Medications and Substances

Johnson¹

2016

View full text Add to dashboard Cite

“…For instance, it has been noted that civilians exposed to industrial organophosphates such as pesticides have a higher incidence of Parkinson's disease (Hatcher et al, 2008;Manthripragada et al, 2010), but it is unknown if nerve agents lead to the same neurodegenerative effects. Acute effects of nerve agents include neuroinflammation (Svensson et al, 2001;Williams et al, 2003;Chapman et al, 2006;Dhote et al, 2007;Dillman et al, 2009), but does this neuroinflammation diminish across time? Are long-term regional differences observed in the brain following nerve agent exposure reflected in large-scale gene expression changes, and can this information be used to correlate gene expression profiles with altered behavioral patterns?…”

Section: Genomics Applications To Cwasmentioning

confidence: 99%

Genomics and proteomics in chemical warfare agent research: Recent studies and future applications

Everley¹,

Dillman²

2010

Toxicology Letters

View full text Add to dashboard Cite

a b s t r a c tMedical research on the effects of chemical warfare agents (CWAs) has been ongoing for nearly 100 years, yet these agents continue to pose a serious threat to deployed military forces and civilian populations. CWAs are extremely toxic, relatively inexpensive, and easy to produce, making them a legitimate weapon of choice for terrorist organizations. While the mechanisms of action for many CWAs have been known for years, questions about their molecular effects following acute and chronic exposure remain largely unanswered. Global approaches that can pinpoint which cellular pathways are altered in response to CWAs and characterize long-term toxicity have not been widely used. Fortunately, innovations in genomics and proteomics technologies now allow for thousands of genes and proteins to be identified and subsequently quantified in a single experiment. Advanced bioinformatics software can also help decipher large-scale changes observed, leading to mapping of signaling pathways, functional characterization, and identification of potential therapeutic targets. Here we present an overview of how genomics and proteomics technologies have been applied to CWA research and also provide a series of questions focused on how these techniques could further our understanding of CWA toxicity.

show abstract

Prolonged inflammatory gene response following soman-induced seizures in mice

Cited by 111 publications

References 49 publications

Neuroprotective mechanisms activated in non-seizing rats exposed to sarin

Neuroprotective mechanisms activated in non-seizing rats exposed to sarin

Assessment of Potential Long Term Health Effects on Army Human Test Subjects of Relevant Biological and Chemical Agents, Drugs, Medications and Substances

Genomics and proteomics in chemical warfare agent research: Recent studies and future applications

Contact Info

Product

Resources

About