Differential phosphoprotein signaling in the cortex in mouse models of Gulf War Illness using corticosterone and acetylcholinesterase inhibitors.

Autor:	Penatzer JA; C. Eugene Bennett Department of Chemistry, West Virginia University, Morvantown, WV, USA., Miller JV; Cardno ChemRisk, Pittsburgh, PA, USA., Prince N; C. Eugene Bennett Department of Chemistry, West Virginia University, Morvantown, WV, USA., Shaw M; Department of Orthopaedics, West Virginia University School of Medicine, Morgantown, WV, USA.; Clinical and Translational Science Institute, West Virginia University School of Medicine, Morgantown, WV, USA., Lynch C; Department of Orthopaedics, West Virginia University School of Medicine, Morgantown, WV, USA., Newman M; Department of Orthopaedics, West Virginia University School of Medicine, Morgantown, WV, USA., Hobbs GR; Department of Statistics, West Virginia University, Morgantown, WV, USA., Boyd JW; Department of Orthopaedics, West Virginia University School of Medicine, Morgantown, WV, USA.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2021 Jul 12; Vol. 7 (7), pp. e07552. Date of Electronic Publication: 2021 Jul 12 (Print Publication: 2021).
DOI:	10.1016/j.heliyon.2021.e07552
Abstrakt:	Aims: Veterans from the 1990-91 Gulf War were exposed to acetylcholinesterase inhibitors (AChEIs), and, following service, an estimated one-third began suffering from a medically unexplained, multi-symptom illness termed Gulf War Illness (GWI). Previous research has developed validated rodent models that include exposure to exogenous corticosterone (CORT) and AChEIs to simulate high stress and chemical exposures encountered in theater. This combination of exposures in mice resulted in a marked increase in neuroinflammation, which is a common symptom of veterans suffering from GWI. To further elucidate the mechanisms associated with these mouse models of GWI, an investigation into intracellular responses in the cortex were performed to characterize the early cellular signaling changes associated with this exposure-initiated neuroinflammation. Main Methods: Adult male C57BL/6J mice were exposed to CORT in the drinking water (200 μg/mL) for 7 days followed by a single intraperitoneal injection of diisopropyl fluorophosphate (DFP; 4.0 mg/kg) or chlorpyrifos oxon (CPO; 8.0 mg/kg), on day 8 and euthanized 0.5, 2, and 24 h post-injection. Eleven post-translationally modified protein targets were measured using a multiplexed ELISA. Key Findings: Phosphoprotein responses were found to be exposure specific following AChEI insult, with and without CORT. Specifically, CORT + CPO exposure was found to sequentially activate several phosphoproteins involved in mitogen activated protein kinase signaling (p-MEK1/2, p-ERK1/2, and p-JNK). DFP alone similarly increased proteins in this pathway (p-RPS6, and p-JNK), but the addition of CORT ameliorated these affects. Significance: The results of this study provide insight into differentially activated pathways depending on AChEI in these GWI models. Competing Interests: The authors declare no conflict of interest. (© 2021 The Authors. Published by Elsevier Ltd.)
Databáze:	MEDLINE
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