Anxiety, neuroinflammation, cholinergic and GABAergic abnormalities are early markers of Gulf War illness in a mouse model of the disease.
Anxiety, neuroinflammation, cholinergic and GABAergic abnormalities are early markers of Gulf War illness in a mouse model of the disease.
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DOI：
10.1016/j.brainres.2017.12.030
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发表时间：
2018-02-15
期刊：
影响因子：
2.9
通讯作者：
Dedeoglu A
中科院分区：
文献类型：
--
作者：
Carreras I;Aytan N;Mellott T;Choi JK;Lehar M;Crabtree L;Leite-Morris K;Jenkins BG;Blusztajn JK;Dedeoglu A
海湾战争病（GWI）是一种慢性疾病，影响1991年海湾战争（GW）退伍军人，缺乏治疗。据推测，在战争期间用于保护军事人员免受化学攻击和昆虫的药物：溴化吡啶斯的明（PB），N，N-二乙基-间甲苯酰胺（DEET）和氯菊酯（PER）与压力一起可能共同和协同地促成了GWI的产生。需要找到用于临床前试验的病理学标志物。为了这个目的，我们采用了一个先前验证的小鼠模型GWI诱发每天暴露于PB（1.3毫克/公斤），避蚊胺（40毫克/公斤），PER（0.13毫克/公斤），和5分钟的束缚应激28天，分析行为，脑病理学和神经化学结果三个月后。GWI模型小鼠的特征在于焦虑增加，N-乙酰天冬氨酸、GABA、GABA产生酶GAD-67和小胶质细胞活化的海马水平降低。我们还观察到，GWI模型在某些措施上是性二态的：男性增加，而女性的乙酰胆碱合成酶，胆碱乙酰转移酶，在隔和海马的蛋白质水平下降，脑源性神经营养因子，TrkB 140，在海马的受体水平下降。仅在雄性动物中检测到海马神经生长因子水平升高。这些数据共同显示了在暴露后3个月检测到的行为和神经病理学异常，其中一些是两性异形的。未来的GWI临床前研究可能会利用这种短潜伏期模型，并应包括男性和女性，因为他们对治疗的反应可能不同。
Gulf War Illness (GWI) is a chronic disease that affects the 1991 Gulf War (GW) veterans for which treatment is lacking. It has been hypothesized that drugs used to protect military personnel from chemical attacks and insects during the war: pyridostigmine bromide (PB), N, N-diethyl-m-toluamide (DEET), and permethrin (PER) together with stress may have contributed collectively and synergistically to generate GWI. There is a need to find markers of pathology to be used in pre-clinical trials. For this purpose we employed a previously validated mouse model of GWI evoked by daily exposure to PB (1.3 mg/kg), DEET (40 mg/kg), PER (0.13 mg/kg), and 5 minutes of restraint stress for 28 days to analyze behavior, brain pathology and neurochemical outcomes three months later. GWI-model mice were characterized by increased anxiety, decreased hippocampal levels of N-acetyl aspartate, GABA, the GABA-producing enzyme GAD-67 and microglial activation. We also observed that GWI model was sexually dimorphic on some measures: males had increased while females had decreased protein levels of the acetylcholine-synthesizing enzyme, choline acetyltransferase, in the septum and hippocampus and decreased levels of the receptor for brain-derived neurotrophic factor, TrkB140, in the hippocampus. Increased hippocampal levels of nerve growth factor were detected in males only. Together the data show behavioral and neuropathological abnormalities detected at 3 months post-exposure and that some of them are sexually dimorphic. Future preclinical studies for GWI may take advantage of this short latency model and should include both males and females as their response to treatment may differ.
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影响因子：
6.1
作者：
Abdel-Rahman, A;Shetty, AK;Abou-Donia, MB
通讯作者：
Abou-Donia, MB
影响因子：
3.8
作者：
Abou-Donia, MB;Goldstein, LB;Khan, WA
通讯作者：
Khan, WA
DOI：
10.1038/npp.2010.104
发表时间：
2011-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Henny, Pablo;Jones, Barbara E.
通讯作者：
Jones, Barbara E.
DOI：
10.1073/pnas.89.2.738
发表时间：
1992-01-15
影响因子：
11.1
作者：
FREUND, TF;MESKENAITE, V
通讯作者：
MESKENAITE, V