Sex-specific expression of pro-inflammatory cytokines in diisopropylfluorophosphate mouse model of epilepsy
Abstract number :
3.072
Submission category :
1. Basic Mechanisms / 1E. Models
Year :
2025
Submission ID :
538
Source :
www.aesnet.org
Presentation date :
12/8/2025 12:00:00 AM
Published date :
Authors :
Maggie Sheridan, NA – Cincinnati Childrens Hosp Medical Center
Ramona Mahadeshwar, NA – Cincinnati Childrens Hosp Medical Center
Christina Gross, PhD – Cincinnati Childrens Hosp Medical Center
Katrina Peariso, MD PhD – University of Cincinnati
Anil Jegga, MD PhD – University of Cincinnati
Presenting Author: Durgesh Tiwari, PhD – University of Cincinnati
Steve Danzer, PhD – Cincinnati Children's Hospital Medical Center
Rationale: Organophosphate (OP) poisoning causes around 300,000 deaths per year. Exposure to OPs leads to long-term comorbidities such as epilepsy, cognitive deficits, and other neurological disorders. Neuroinflammation is a critical mechanism of seizure development that can be targeted to treat OP-associated adverse effects. This research aims to explore sex-specific effects of OPs on key neuroinflammatory cytokine expression using mouse model. DFP was used as the surrogate organophosphate.
Methods: Dose optimization was performed with 8, 9.5, and 12 mg/kg DFP and electrographic seizures were observed. Brains were harvested at 1 hour, 4 hours, 24 hours, 3 days, and 7 days post-DFP exposure. Time-dependent expression of pro-inflammatory cytokines IL1b, IL6, and TNFa in male and female mice dosed with 9.5 mg/kg DFP was investigated using qPCR in both hippocampal and cortical tissues.
Results: . In DFP-treated male mice, hippocampal samples showed a trend toward increased IL1b compared to saline control, with results approaching significance at 1 and 24 hours post-exposure (p = 0.0708 and 0.0639, respectively). No consistent trend was observed in IL6 expression across four of five timepoints, but a significant difference was seen at 4 hours (p = 0.0471). TNFa showed a trend towards increased expression from 1 to 24 hours, with significance at 4 and 24 hours (p = 0.0012 and 0.0449, respectively). In cortical samples, a trend toward increased IL1b (p = 0.0388 at 1 hour) and significantly greater TNFa expression at 1 hour (p = 0.05) was observed compared to saline control. In female mice, cortical tissues showed a similar expression to male cortex at 1 hour, with increased IL1b and TNFa (p > 0.05) and comparable IL6 relative to controls. However, unlike male hippocampus, female hippocampus showed no difference in expression in any of the cytokines.
Conclusions: These findings can help design novel therapies targeting neuroinflammation in OP poisoning.
Funding: JIT-CCHMC (D.T), CCTST-MTRS CCHMC (D.T.), a postdoctoral fellowship from the American Epilepsy Society (D.T
Basic Mechanisms