Corticosterone primes the neuroinflammatory response to Gulf War Illness-relevant organophosphates independently of acetylcholinesterase inhibition

Journal of Neurochemistry
Alicia R LockerJames P O'Callaghan

Abstract

Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting veterans of the 1991 Gulf War. Among the symptoms of GWI are those associated with sickness behavior, observations suggestive of underlying neuroinflammation. We have shown that exposure of mice to the stress hormone, corticosterone (CORT), and to diisopropyl fluorophosphate (DFP), as a nerve agent mimic, results in marked neuroinflammation, findings consistent with a stress/neuroimmune basis of GWI. Here, we examined the contribution of irreversible and reversible acetylcholinesterase (AChE) inhibitors to neuroinflammation in our mouse model of GWI. Male C57BL/6J mice received 4 days of CORT (400 mg/L) in the drinking water followed by a single dose of chlorpyrifos oxon (CPO; 8 mg/kg, i.p.), DFP (4 mg/kg, i.p.), pyridostigmine bromide (PB; 3 mg/kg, i.p.), or physostigmine (PHY; 0.5 mg/kg, i.p.). CPO and DFP alone caused cortical and hippocampal neuroinflammation assessed by qPCR of tumor necrosis factor-alpha, IL-6, C-C chemokine ligand 2, IL-1β, leukemia inhibitory factor and oncostatin M; CORT pretreatment markedly augmented these effects. Additionally, CORT exposure prior to DFP or CPO enhanced activation of the neuroinflammation signal transducer, signal ...Continue Reading

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Citations

May 31, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Julie V MillerJames P O'Callaghan
Mar 7, 2020·Brain Sciences·Byron C JonesJames P O'Callaghan
Jan 8, 2020·The Journal of Pharmacology and Experimental Therapeutics·Kyle A BrownJohn J Wagner
Oct 20, 2019·Military Medical Research·Jeremy E ChesterDrew A Helmer
May 14, 2020·International Journal of Environmental Research and Public Health·Chelsey PoissonPollie Bith-Melander
May 16, 2020·Frontiers in Physiology·Saurabh VashishthaNancy G Klimas
Oct 31, 2018·Frontiers in Cellular Neuroscience·Travis J A CraddockGordon Broderick
Feb 7, 2020·Brain, Behavior, and Immunity·Zeynab AlshelhMarco L Loggia
Nov 1, 2020·Brain, Behavior, and Immunity·Michael J LacagninaPeter M Grace
Jun 24, 2020·Brain, Behavior, and Immunity·Fuyi XuLu Lu
Nov 10, 2020·Pharmacology & Therapeutics·Brandon DickeyAshok K Shetty
Oct 16, 2019·Metabolism: Clinical and Experimental·James P O'Callaghan, Diane B Miller
Jul 22, 2019·Brain, Behavior, and Immunity·Utsav JoshiLaila Abdullah
Nov 2, 2019·Toxicology Reports·Jacqueline Freire MachiMariana Morris
Jun 26, 2021·Pharmacology & Therapeutics·Ana C R Ribeiro, Laxmikant S Deshpande
Jul 20, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Julia A PenatzerJonathan W Boyd
Aug 28, 2021·International Journal of Molecular Sciences·Francisco J Carrera AriasTravis J A Craddock

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Methods Mentioned

BETA
ELISA
dissection
protein assay
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SCR_003210

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Excel
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