| Title : Acute gene expression changes in the mouse hippocampus following a combined Gulf War toxicant exposure - Murray_2021_Life.Sci__119845 |
| Author(s) : Murray KE , Delic V , Ratliff WA , Beck KD , Citron BA |
| Ref : Life Sciences , :119845 , 2021 |
| Abstract : 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 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. |
| ESTHER : Murray_2021_Life.Sci__119845 |
| PubMedSearch : Murray_2021_Life.Sci__119845 |
| PubMedID: 34293396 |
Murray KE, Delic V, Ratliff WA, Beck KD, Citron BA (2021)
Acute gene expression changes in the mouse hippocampus following a combined Gulf War toxicant exposure
Life Sciences
:119845
Murray KE, Delic V, Ratliff WA, Beck KD, Citron BA (2021)
Life Sciences
:119845