Lentivirus-mediated interleukin-1β (IL-1β) knock-down in the hippocampus alleviates lipopolysaccharide (LPS)-induced memory deficits and anxiety- and depression-like behaviors in mice.
Lentivirus-mediated interleukin-1β (IL-1β) knock-down in the hippocampus alleviates lipopolysaccharide (LPS)-induced memory deficits and anxiety- and depression-like behaviors in mice.
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慢病毒介导的海马白介素 1 β (IL-1 β) 敲低可减轻脂多糖 (LPS) 诱导的小鼠记忆缺陷以及焦虑和抑郁样行为
DOI：
10.1186/s12974-017-0964-9
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发表时间：
2017-09-20
影响因子：
9.3
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Li M;Li C;Yu H;Cai X;Shen X;Sun X;Wang J;Zhang Y;Wang C
最近的证据表明，脂多糖诱导的外周炎症反应在啮齿类动物的神经精神功能障碍中起着重要作用。白细胞介素1受体(IL-1β，IL-1β)是一种促炎细胞因子，在脂多糖诱导的小鼠多种行为功能障碍中起关键作用。因此，抑制IL-1β可能在治疗神经精神障碍方面有疗效。然而，下调IL-1β修复内毒素引起的行为改变的确切机制尚不清楚。小鼠接受IL-1βshRNA慢病毒或非沉默shRNA对照(NS ShRNA)慢病毒的治疗，方法是向海马齿状回(DG)区微量注射。恢复7天后，腹腔注射脂多糖(1 mg/kg)。或者注射生理盐水。用新型物体识别试验(NORT)进行记忆障碍的行为测试，用高架零迷宫(EZM)评价焦虑样行为，用蔗糖偏爱试验(SPT)和强迫游泳试验(FST)评价抑郁样行为。检测血清丙二醛、超氧化物歧化酶、核因子红系衍生型2、血红素加氧酶1、白介素1β、肿瘤坏死因子α、神经肽类生长因子、脑源性神经营养因子的水平。我们的结果表明，海马区IL-1β的敲除显著减轻了脂多糖诱导的小鼠的记忆障碍以及焦虑和抑郁样行为。此外，IL-1β基因敲除可改善氧化反应和神经炎性反应，并取消脂多糖诱导的血管内皮生长因子和脑源性神经营养因子的下调。综上所述，我们的研究结果表明，IL-1VGF对脂多糖引起的氧化和神经炎性反应是必需的，并在IL-1β/oxidative/neuroinflammatory/neurotrophic途径中提供了一个新的药物靶点，用于治疗与神经炎症、氧化应激以及β和BDNFmRNA下调密切相关的神经精神障碍。
Recent evidence has suggested that peripheral inflammatory responses induced by lipopolysaccharides (LPS) play an important role in neuropsychiatric dysfunction in rodents. Interleukin-1β (IL-1β), a pro-inflammatory cytokine, has been proposed to be a key mediator in a variety of behavioral dysfunction induced by LPS in mice. Thus, inhibition of IL-1β may have a therapeutic benefit in the treatment of neuropsychiatric disorders. However, the precise underlying mechanism of knock-down of IL-1β in repairing behavioral changes by LPS remains unclear. The mice were treated with either IL-1β shRNA lentivirus or non-silencing shRNA control (NS shRNA) lentivirus by microinjection into the dentate gyrus (DG) regions of the hippocampus. After 7 days of recovery, LPS (1 mg/kg, i.p.) or saline was administered. The behavioral task for memory deficits was conducted in mice by the novel object recognition test (NORT), the anxiety-like behaviors were evaluated by the elevated zero maze (EZM), and the depression-like behaviors were examined by the sucrose preference test (SPT) and the forced swimming test (FST). Furthermore, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor erythroid-derived 2-like 2 (Nrf2), heme oxygenase 1 (HO1), IL-1β, tumor necrosis factor (TNF-α), neuropeptide VGF (non-acronymic), and brain-derived neurotrophic factor (BDNF) were assayed. Our results demonstrated that IL-1β knock-down in the hippocampus significantly attenuated the memory deficits and anxiety- and depression-like behaviors induced by LPS in mice. In addition, IL-1β knock-down ameliorated the oxidative and neuroinflammatory responses and abolished the downregulation of VGF and BDNF induced by LPS. Collectively, our findings suggest that IL-1β is necessary for the oxidative and neuroinflammatory responses produced by LPS and offers a novel drug target in the IL-1β/oxidative/neuroinflammatory/neurotrophic pathway for treating neuropsychiatric disorders that are closely associated with neuroinflammation, oxidative stress, and the downregulation of VGF and BDNF.
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影响因子：
9.3
作者：
Ito N;Hirose E;Ishida T;Hori A;Nagai T;Kobayashi Y;Kiyohara H;Oikawa T;Hanawa T;Odaguchi H
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