Persistent exercise fatigue and associative learning deficits in combination with transient glucose dyshomeostasis in a mouse model of Gulf War Illness.
Persistent exercise fatigue and associative learning deficits in combination with transient glucose dyshomeostasis in a mouse model of Gulf War Illness.
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DOI：
10.1016/j.lfs.2021.120094
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发表时间：
2022-01-15
期刊：
影响因子：
6.1
通讯作者：
Curras-Collazo, Margarita C.
中科院分区：
文献类型：
--
作者：
Kozlova, Elena, V;Carabelli, Bruno;Bishay, Anthony E.;Denys, Maximillian E.;Chinthirla, Devi B.;Tran, Jasmin D.;Hsiao, Ansel;Zur Nieden, Nicole, I;Curras-Collazo, Margarita C.
关键词：
描述慢性海湾战争病（GWI）小鼠模型中与脑神经炎症和肠道微生物组变化相关的运动疲劳、代谢表型以及认知和情绪缺陷。后者已在所附文件中作了说明。成年雄性C57 Bl/6 N小鼠暴露于溴化吡啶斯的明28天（5天/周）：6.5 mg/kg，b.i.d.，P.O. (GW1)或8.7 mg/kg，q.d.，P.O. (GW2)局部二氯苯醚菊酯（1.3 mg/kg，溶于100%DMSO）和N，N-二乙基间甲苯酰胺（DEET 33%，溶于70%EtOH）和束缚应激（5 min）。将运动、代谢和行为终点与假应激对照（CON/S）进行比较。相对于CON/S，GW 2表现出持续的运动不耐受（至治疗后（PT）第161天）、缺乏联想学习/记忆和一过性胰岛素不敏感。与GW 2相比，GW 1表现出缺乏长期物体识别记忆，轻度联想学习/记忆缺陷和行为绝望。我们的研究结果表明，GW化学物质剂量依赖性地确定运动疲劳的表现和表现出持久性的认知/情绪缺陷表型的严重程度/类型。我们的GWI综合小鼠模型概括了GWI的主要多个症状领域，包括疲劳和认知障碍，可用于更有效地为患病的海湾战争退伍军人开发诊断测试和治疗方法。
To characterize exercise fatigue, metabolic phenotype and cognitive and mood deficits correlated with brain neuroinflammatory and gut microbiome changes in a chronic Gulf War Illness (GWI) mouse model. The latter have been described in an accompanying paper. Adult male C57Bl/6N mice were exposed for 28 days (5 days/week) to pyridostigmine bromide: 6.5 mg/kg, b.i.d., P.O. (GW1) or 8.7 mg/kg, q.d., P.O. (GW2); topical permethrin (1.3 mg/kg in 100% DMSO) and N,N-diethyl-meta-toluamide (DEET 33% in 70% EtOH) and restraint stress (5 min). Exercise, metabolic and behavioral endpoints were compared to sham stress control (CON/S). Relative to CON/S, GW2 presented persistent exercise intolerance (through post-treatment (PT) day 161), deficient associative learning/memory, and transient insulin insensitivity. In contrast to GW2, GW1 showed deficient long-term object recognition memory, milder associative learning/memory deficit, and behavioral despair. Our findings demonstrate that GW chemicals dose-dependently determine the presentation of exercise fatigue and severity/type of cognitive/mood-deficient phenotypes that show persistence. Our comprehensive mouse model of GWI recapitulates the major multiple symptom domains characterizing GWI, including fatigue and cognitive impairment that can be used to more efficiently develop diagnostic tests and curative treatments for ill Gulf War veterans.
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影响因子：
4.5
作者：
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通讯作者：
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影响因子：
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作者：
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6.1
作者：
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DOI：
10.1037/h0077579
发表时间：
1979-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
BARNES, CA
通讯作者：
BARNES, CA