Gulf War toxicant-induced reductions in dendritic arbors and spine densities of dentate granule cells are improved by treatment with a Nrf2 activator.

Autor: Murray KE; Laboratory of Molecular Biology, Research & Development, Department of Veterans Affairs, VA New Jersey Health Care System, East Orange, NJ 07018, USA; School of Graduate Studies, Rutgers University, Newark, NJ 07103, USA., Ratliff WA; Research & Development, Department of Veterans Affairs, Bay Pines VA Healthcare System, Bay Pines, FL 33744, USA., Delic V; Laboratory of Molecular Biology, Research & Development, Department of Veterans Affairs, VA New Jersey Health Care System, East Orange, NJ 07018, USA; School of Graduate Studies, Rutgers University, Newark, NJ 07103, USA; Department of Pharmacology, Physiology, and Neuroscience, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA., Citron BA; Laboratory of Molecular Biology, Research & Development, Department of Veterans Affairs, VA New Jersey Health Care System, East Orange, NJ 07018, USA; School of Graduate Studies, Rutgers University, Newark, NJ 07103, USA; Department of Pharmacology, Physiology, and Neuroscience, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA. Electronic address: bruce.citron@rutgers.edu.
Jazyk: angličtina
Zdroj: Brain research [Brain Res] 2024 Jan 15; Vol. 1823, pp. 148682. Date of Electronic Publication: 2023 Nov 19.
DOI: 10.1016/j.brainres.2023.148682
Abstrakt: Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting approximately 30 % of Veterans deployed to the Persian Gulf from 1990 to 91. GWI encompasses a wide spectrum of symptoms which frequently include neurological problems such as learning and memory impairments, mood disorders, and an increased incidence of neurodegenerative disorders. Combined exposure to both reversible and irreversible acetylcholinesterase (AChE) inhibitors has been identified as a likely risk factor for GWI. It is possible that the exposures affected connectivity in the brain, and it was also unknown whether this could benefit from treatment. We assessed chronic changes in dendritic architecture in granule cells of the dentate gyrus following exposure to pyridostigmine bromide (PB, 0.7 mg/kg), chlorpyrifos (CPF, 12.5 mg/kg), and N,N-diethyl-m-toluamide (DEET, 7.5 mg/kg) in male C57Bl/6J mice. We also evaluated the therapeutic effects of dietary administration for eight weeks of 1 % tert-butylhydroquinone (tBHQ), a Nrf2 activator, on long-term neuronal morphology. We found that Gulf War toxicant exposure resulted in reduced dendritic length and branching as well as overall spine density in dentate granule cells at 14 weeks post-exposure and that these effects were ameliorated by treatment with tBHQ. These findings indicate that Gulf War toxicant exposure results in chronic changes to dentate granule cell morphology and that modulation of neuroprotective transcription factors such as Nrf2 may improve long-term neuronal health in the hippocampus.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Published by Elsevier B.V.)
Databáze: MEDLINE
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