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• W3047504804 endingPage "108264" @default.
• W3047504804 startingPage "108264" @default.
• W3047504804 abstract "Gulf War Illness (GWI) is a chronic multisymptom illness that includes gastrointestinal disorders. Although the exact etiology of GWI is unknown, exposure to the drug pyridostigmine bromide (PB) is considered a major factor. Exposure to PB drives enteric neuroinflammation, promotes immunosuppression, and alters physiological functions of the colon in the short term but whether exposure to PB is sufficient to promote long term dysfunction is not known. Here, we tested whether exposure to PB is sufficient to drive long term changes that reflect GWI, and whether the endogenous anti-inflammatory mediator palmitoylethanolamide (PEA) is sufficient to reduce the detrimental effects of PB in the gut and brain of mice. Exposure to PB alone was not sufficient to cause major changes in neuromuscular transmission but did drive major changes by altering the effects of PEA. Calcium imaging data show that the mechanisms responsible include a shift in receptor signaling mediated by TRPV1, endocannabinoids, and peroxisome proliferator-activated receptors alpha (PPARα). Additional mechanisms include the development of glial reactivity and changes in enteric neurochemical coding and survival. PB and PEA caused major shifts in pro-inflammatory cytokines/chemokines in the brain and colon that persisted up to 5 months following exposure. Many of the effects of PB and PEA exhibit significant sex differences. Together, these results highlight novel mechanisms whereby PB promotes long-lasting changes in nervous system and immune function by inducing occult neuroplasticity that is revealed by subsequent exposure to unrelated drugs in a sex dependent manner." @default.
• W3047504804 created "2020-08-10" @default.
• W3047504804 creator A5003083025 @default.
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• W3047504804 creator A5058570442 @default.
• W3047504804 creator A5080270849 @default.
• W3047504804 creator A5085553468 @default.
• W3047504804 date "2020-11-01" @default.
• W3047504804 modified "2023-09-28" @default.
• W3047504804 title "Pyridostigmine bromide exposure creates chronic, underlying neuroimmune disruption in the gastrointestinal tract and brain that alters responses to palmitoylethanolamide in a mouse model of Gulf War Illness" @default.
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• W3047504804 doi "https://doi.org/10.1016/j.neuropharm.2020.108264" @default.
• W3047504804 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7572863" @default.
• W3047504804 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32758565" @default.
• W3047504804 hasPublicationYear "2020" @default.
• W3047504804 type Work @default.

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