Voluntary exercise protects hippocampal neurons from trimethyltin injury: possible role of interleukin-6 to modulate tumor necrosis factor receptor-mediated neurotoxicity.
Voluntary exercise protects hippocampal neurons from trimethyltin injury: possible role of interleukin-6 to modulate tumor necrosis factor receptor-mediated neurotoxicity.
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DOI：
10.1016/j.bbi.2011.03.012
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发表时间：
2011-08
影响因子：
15.1
通讯作者：
Harry, G. Jean
中科院分区：
文献类型：
--
作者：
Funk, Jason A.;Gohlke, Julia;Kraft, Andrew D.;McPherson, Christopher A.;Collins, Jennifer B.;Harry, G. Jean
在外周，运动诱导白细胞介素（IL）-6下调肿瘤坏死因子（TNF），升高白细胞介素-1受体拮抗剂（IL-1 RA），减少炎症。运动还提供神经保护，促进大脑修复。运动后海马体中IL-6的产生表明其可能具有与外周类似的保护作用，以下调TNFα和炎症。使用依赖于TNF受体信号传导的化学诱导的海马齿状核颗粒细胞死亡模型（三甲基锡，TMT 2.4mg/kg，ip），我们证明了在小鼠中使用2周的转轮的神经保护作用。运动可减轻神经元死亡，并降低TNFα、TNF受体1、髓样分化初级反应基因（MyD）88、转化生长因子β、趋化因子（C-C基序）配体2（CCL 2）和CCL 3的升高。IL-1α、IL-1 RA的mRNA水平升高与损伤和保护有关。IL-6的mRNA和蛋白水平以及IL-6受体α的神经元表达随着损伤和保护而升高。微阵列通路分析支持TMT上调TNFα细胞死亡信号通路和运动抑制。IL-6通路募集在两种情况下都发生。IL-6下游信号事件在STAT 3活化水平上不同。运动没有增加脑源性神经营养因子、神经生长因子或胶质源性神经营养因子的mRNA水平。在IL-6缺乏的小鼠中，运动并没有减弱TMT诱导的震颤，并且观察到神经保护水平降低。这些数据表明，运动诱导的IL-6对中枢神经系统的神经保护作用与在外周神经系统中观察到的作用相似。
In the periphery, exercise induces interleukin (IL)-6 to downregulate tumor necrosis factor (TNF), elevate interleukin-1 receptor antagonist (IL-1RA), decreasing inflammation. Exercise also offers neuroprotection and facilitates brain repair. IL-6 production in the hippocampus following exercise suggests the potential of a similar protective role as in the periphery to down-regulate TNFα and inflammation. Using a chemical-induced model of hippocampal dentate granule cell death (trimethyltin, TMT 2.4 mg/kg, ip) dependent upon TNF receptor signaling, we demonstrate neuroprotection in mice with 2wks access to running wheel. Exercise attenuated neuronal death and diminished elevations in TNFα, TNF receptor 1, myeloid differentiation primary response gene (MyD) 88, transforming growth factor β, chemokine (C-C motif) ligand 2 (CCL2), and CCL3. Elevated mRNA levels for IL-1α, IL-1RA, occurred with injury and protection. mRNA and protein levels of IL-6 and neuronal expression of IL-6 receptor α, were elevated with injury and protection. Microarray pathway analysis supported an up-regulation of TNFα cell death signaling pathways with TMT and inhibition by exercise. IL-6 pathway recruitment occurred in both conditions. IL-6 downstream signal events differed in the level of STAT3 activation. Exercise did not increase mRNA levels of brain derived neurotrophic factor, nerve growth factor, or glial derived neurotrophic factor. In IL-6 deficient mice, exercise did not attenuate TMT-induced tremor and a diminished level of neuroprotection was observed. These data suggest a contributory role for IL-6 induced by exercise for neuroprotection in the CNS similar to that seen in the periphery.
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创伤后，通过上调白介素（IL）6和IL-6受体的表达来加速小鼠的神经再生。
影响因子：
15.3
作者：
Hirota, H;Kiyama, H;Kishimoto, T;Taga, T
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影响因子：
10.5
作者：
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Day HE
影响因子：
5.5
作者：
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影响因子：
64.8
作者：
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通讯作者：
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