Acute gene expression changes in the mouse hippocampus following a combined Gulf War toxicant exposure.

Autor: Murray KE; Laboratory of Molecular Biology, VA New Jersey Health Care System, Research & Development (Mailstop 15), Bldg. 16, Rm. 16-176, 385 Tremont Ave, East Orange, NJ 07018, United States of America; Rutgers School of Graduate Studies, Newark, NJ 07103, United States of America. Electronic address: kathleen.murray@rutgers.edu., Delic V; Laboratory of Molecular Biology, VA New Jersey Health Care System, Research & Development (Mailstop 15), Bldg. 16, Rm. 16-176, 385 Tremont Ave, East Orange, NJ 07018, United States of America; Rutgers School of Graduate Studies, Newark, NJ 07103, United States of America; Pharmacology, Physiology, and Neuroscience, Rutgers-New Jersey Medical School, Newark, NJ 07103, United States of America. Electronic address: vedad.delic@rutgers.edu., Ratliff WA; Laboratory of Molecular Biology, Bay Pines VA Healthcare System, Research and Development, 151, Bldg. 22, Rm. 123, 10000 Bay Pines Blvd, Bay Pines, FL 33744, United States of America. Electronic address: whitney.ratliff@va.gov., Beck KD; Neurobehavior Research Laboratory, VA New Jersey Health Care System, Research & Development (Mailstop 15), Bldg. 16, Rm. 16-176, 385 Tremont Ave, East Orange, NJ 07018, United States of America; Rutgers School of Graduate Studies, Newark, NJ 07103, United States of America; Pharmacology, Physiology, and Neuroscience, Rutgers-New Jersey Medical School, Newark, NJ 07103, United States of America. Electronic address: kevin.beck@va.gov., Citron BA; Laboratory of Molecular Biology, VA New Jersey Health Care System, Research & Development (Mailstop 15), Bldg. 16, Rm. 16-176, 385 Tremont Ave, East Orange, NJ 07018, United States of America; Rutgers School of Graduate Studies, Newark, NJ 07103, United States of America; Laboratory of Molecular Biology, Bay Pines VA Healthcare System, Research and Development, 151, Bldg. 22, Rm. 123, 10000 Bay Pines Blvd, Bay Pines, FL 33744, United States of America; Pharmacology, Physiology, and Neuroscience, Rutgers-New Jersey Medical School, Newark, NJ 07103, United States of America. Electronic address: bruce.citron@rutgers.edu.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 Nov 01; Vol. 284, pp. 119845. Date of Electronic Publication: 2021 Jul 20.
DOI: 10.1016/j.lfs.2021.119845
Abstrakt: Aims: Approximately 30% of the nearly 700,000 Veterans who were deployed to the Gulf War from 1990 to 1991 have reported experiencing a variety of symptoms including difficulties with learning and memory, depression and anxiety, and increased incidence of neurodegenerative diseases. Combined toxicant exposure to acetylcholinesterase (AChE) inhibitors has been studied extensively as a likely risk factor. In this study, we modeled Gulf War exposure in male C57Bl/6J mice with simultaneous administration of three chemicals implicated as exposure hazards for Gulf War Veterans: pyridostigmine bromide, the anti-sarin prophylactic; chlorpyrifos, an organophosphate insecticide; and the repellant N,N-diethyl-m-toluamide (DEET).
Main Methods: Following two weeks of daily exposure, we examined changes in gene expression by whole transcriptome sequencing (RNA-Seq) with hippocampal isolates. Hippocampal-associated spatial memory was assessed with a Y-maze task. We hypothesized that genes important for neuronal health become dysregulated by toxicant-induced damage and that these detrimental inflammatory gene expression profiles could lead to chronic neurodegeneration.
Key Findings: We found dysregulation of genes indicating a pro-inflammatory response and downregulation of genes associated with neuronal health and several important immediate early genes (IEGs), including Arc and Egr1, which were both reduced approximately 1.5-fold. Mice exposed to PB + CPF + DEET displayed a 1.6-fold reduction in preference for the novel arm, indicating impaired spatial memory.
Significance: Differentially expressed genes observed at an acute timepoint may provide insight into the pathophysiology of Gulf War Illness and further explanations for chronic neurodegeneration after toxicant exposure.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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