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.
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.
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在海湾战争病小鼠模型中，溴化吡啶斯的明暴露在胃肠道和大脑中引起慢性、潜在的神经免疫破坏，改变了对棕榈酰乙醇胺的反应。
DOI：
10.1016/j.neuropharm.2020.108264
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发表时间：
2020-11-15
影响因子：
4.7
通讯作者：
Gulbransen BD
中科院分区：
文献类型：
--
作者：
Hernandez S;Morales-Soto W;Grubišić V;Fried D;Gulbransen BD
海湾战争病（GWI）是一种慢性多症状疾病，包括胃肠道疾病。虽然GWI的确切病因尚不清楚，但暴露于溴化吡啶斯的明（PB）被认为是一个主要因素。暴露于PB会驱动肠道神经炎症，促进免疫抑制，并在短期内改变结肠的生理功能，但暴露于PB是否足以促进长期功能障碍尚不清楚。在这里，我们测试了暴露于PB是否足以驱动反映GWI的长期变化，以及内源性抗炎介质棕榈酰乙醇酰胺（PEA）是否足以减少PB在小鼠肠道和大脑中的有害影响。单独暴露于PB不足以引起神经肌肉传递的重大变化，但确实通过改变PEA的作用而引起重大变化。钙成像数据显示，相关机制包括TRPV 1、内源性大麻素和过氧化物酶体增殖物激活受体α（PPARα）介导的受体信号传导的转变。其他机制包括神经胶质反应性的发展和肠道神经化学编码和存活的变化。PB和PEA引起大脑和结肠中促炎细胞因子/趋化因子的重大变化，持续至暴露后5个月。PB和PEA的许多效应表现出显著的性别差异。总之，这些结果突出了新的机制，PB促进神经系统和免疫功能的持久变化，通过诱导隐性神经可塑性，揭示了随后暴露于不相关的药物在性别依赖的方式。
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.
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影响因子：
4
作者：
Beggiato, Sarah;Borelli, Andrea Celeste;Tomasini, Maria Cristina
通讯作者：
Tomasini, Maria Cristina
DOI：
10.1124/jpet.112.197871
发表时间：
2013-01-01
影响因子：
3.5
作者：
Freitas, Kelen;Carroll, F. Ivy;Damaj, M. Imad
通讯作者：
Damaj, M. Imad
影响因子：
3.3
作者：
De Filippis, Daniele;Luongo, Livio;Iuvone, Teresa
通讯作者：
Iuvone, Teresa
影响因子：
1.8
作者：
Cerrato, S.;Brazis, P.;Puigdemont, A.
通讯作者：
Puigdemont, A.
影响因子：
6.1
作者：
Abdel-Rahman, A;Shetty, AK;Abou-Donia, MB
通讯作者：
Abou-Donia, MB