Oleoylethanolamide treatment reduces neurobehavioral deficits and brain pathology in a mouse model of Gulf War Illness.
Oleoylethanolamide treatment reduces neurobehavioral deficits and brain pathology in a mouse model of Gulf War Illness.
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DOI：
10.1038/s41598-018-31242-7
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发表时间：
2018-08-27
影响因子：
4.6
通讯作者：
Abdullah L
中科院分区：
文献类型：
--
作者：
Joshi U;Evans JE;Joseph R;Emmerich T;Saltiel N;Lungmus C;Oberlin S;Langlois H;Ojo J;Mouzon B;Paris D;Mullan M;Jin C;Klimas N;Sullivan K;Crawford F;Abdullah L
有近250，000名海湾战争（GW）退伍军人患有海湾战争疾病（GWI），这是一种无法治愈的多症状疾病。主要目的是确定靶向过氧化物酶体功能是否对GWI具有治疗价值。我们进行了一项初步研究，显示患有GWI的退伍军人血浆中存在极长链脂肪酸（VLCFA）的积累，这些脂肪酸在过氧化物酶体中代谢。然后，我们检查了用油酰乙醇胺（OEA）靶向过氧化物酶体β-氧化是否将这些脂质恢复到正常水平，并在良好建立的GWI小鼠模型中减轻神经炎症和神经行为缺陷。在GWI小鼠中，用OEA治疗与GWI小鼠的认知益处和减少的疲劳和解除抑制样行为相对应。脑组织的生化和分子分析显示星形胶质细胞和小胶质细胞染色减少，趋化因子和细胞因子水平降低，NFκB磷酸化降低。用OEA处理减少了GWI小鼠脑中过氧化物酶体特异性VLCFA的积累。这些研究进一步支持靶向过氧化物酶体的翻译价值。我们期望OEA可能是治疗神经行为症状和与GWI相关的潜在脂质功能障碍和神经炎症的潜在疗法。油酰乙醇胺可作为膳食补充剂，使其对人类转化研究具有吸引力。
There are nearly 250,000 Gulf War (GW) veterans who suffer from Gulf War Illness (GWI), a multi-symptom condition that remains untreatable. The main objective was to determine if targeting peroxisomal function could be of therapeutic value in GWI. We performed a pilot study that showed accumulation of very long chain fatty acids (VLCFA), which are metabolized in peroxisomes, in plasma from veterans with GWI. We then examined if targeting peroxisomal β-oxidation with oleoylethanolamide (OEA) restores these lipids to the normal levels and mitigates neuroinflammation and neurobehavioral deficits in a well-established mouse model of GWI. In GWI mice, treatment with OEA corresponded with cognitive benefits and reduced fatigue and disinhibition-like behavior in GWI mice. Biochemical and molecular analysis of the brain tissue showed reduced astroglia and microglia staining, decreased levels of chemokines and cytokines, and decreased NFκB phosphorylation. Treatment with OEA reduced accumulation of peroxisome specific VLCFA in the brains of GWI mice. These studies further support the translational value of targeting peroxisomes. We expect that OEA may be a potential therapy for treating neurobehavioral symptoms and the underlying lipid dysfunction and neuroinflammation associated with GWI. Oleoylethanolamide is available as a dietary supplement, making it appealing for human translational studies.
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影响因子：
4.5
作者：
Abdullah, Laila;Evans, James E.;Crawford, Fiona
通讯作者：
Crawford, Fiona
影响因子：
3.5
作者：
Abdullah, Laila;Crynen, Gogce;Crawford, Fiona
通讯作者：
Crawford, Fiona
DOI：
10.1073/pnas.0903038106
发表时间：
2009-05-12
影响因子：
11.1
作者：
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通讯作者：
Piomelli, Daniele
影响因子：
4.8
作者：
Chen, Keqiang;Liu, Mingyong;Wang, Ji Ming
通讯作者：
Wang, Ji Ming
影响因子：
23.9
作者：
Boldrini M;Fulmore CA;Tartt AN;Simeon LR;Pavlova I;Poposka V;Rosoklija GB;Stankov A;Arango V;Dwork AJ;Hen R;Mann JJ
通讯作者：
Mann JJ