Insulin-like growth factor-1 abrogates microglial oxidative stress and TNF-α responses to spreading depression.
Insulin-like growth factor-1 abrogates microglial oxidative stress and TNF-α responses to spreading depression.
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DOI：
10.1111/jnc.12267
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发表时间：
2013-09
影响因子：
4.7
通讯作者：
Kraig RP
中科院分区：
文献类型：
--
作者：
Grinberg YY;Dibbern ME;Levasseur VA;Kraig RP
扩散性抑郁（SD）是偏头痛先兆和偏头痛的最可能原因，伴随氧化应激（OS）增加而发生。SD增加活性氧（ROS），而ROS又可以发出信号以增加神经元兴奋性，包括增加SD易感性（SDS）。SD还升高肿瘤坏死因子-α（TNF-α），从而增加神经元兴奋性。因此，本研究采用大鼠海马脑片培养方法，探讨SD大鼠OS的细胞来源及其与TNF-α的关系。我们观察到从SD星形胶质细胞和小胶质细胞OS显着增加，但在神经元或少突胶质细胞。由于胰岛素样生长因子-1（IGF-1）可减轻SD的OS，因此我们确定了导致这种效应的细胞类型。我们发现，IGF-1显着降低小胶质细胞，但不是星形胶质细胞OS从SD。我们还发现，IGF-1消除了SD诱导的TNF-α增加。此外，TNF-α的应用增加了小胶质细胞的OS，而不是星形胶质细胞的OS，IGF-1消除了这种作用。接下来，我们发现SD增加SDS，并通过TNF-α实现。这项工作表明，小胶质细胞通过增加和相关的ROS和TNF-α信号传导促进SD。因此，IGF-1缓解小胶质细胞ROS和TNF-α反应可能是预防SD和偏头痛的新疗法开发的目标。
Spreading depression (SD), the most likely cause of migraine aura and perhaps migraine, occurs with increased oxidative stress (OS). SD increases reactive oxygen species (ROS), and ROS, in turn, can signal to increase neuronal excitability, which includes increased SD susceptibility (SDS). SD also elevates tumor necrosis factor-α (TNF-α), which increases neuronal excitability. Accordingly, we probed for the cellular origin of OS from SD and its relationship to TNF-α, which might promote SD, using rat hippocampal slice cultures. We observed significantly increased OS from SD in astrocytes and microglia but not in neurons or oligodendrocytes. Since insulin-like growth factor-1 (IGF-1) mitigates OS from SD, we determined the cell types responsible for this effect. We found that IGF-1 significantly decreased microglial but not astrocytic OS from SD. We also show that IGF-1 abrogated the SD-induced TNF-α increase. Furthermore, TNF-α application increased microglial but not astrocytic OS, an effect abrogated by IGF-1. Next, we showed that SD increased SDS, and does so via TNF-α. This work suggests that microglia promote SD via increased and interrelated ROS and TNF-α signaling. Thus, IGF-1 mitigation of microglial ROS and TNF-α responses may be targets for novel therapeutics development to prevent SD, and perhaps migraine.
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影响因子：
5.3
作者：
Cipolla, Marilyn J.;Pusic, Aya D.;Grinberg, Yelena Y.;Chapman, Abbie C.;Poynter, Matthew E.;Kraig, Richard P.
通讯作者：
Kraig, Richard P.
影响因子：
4.7
作者：
Grinberg YY;van Drongelen W;Kraig RP
通讯作者：
Kraig RP
DOI：
10.1097/01.wcb.0000126566.34753.30
发表时间：
2004-08-01
影响因子：
6.3
作者：
Kunkler, PE;Hulse, RE;Kraig, TP
通讯作者：
Kraig, TP
DOI：
10.1097/00004647-199701000-00005
发表时间：
1997-01-01
影响因子：
6.3
作者：
Kunkler, PE;Kraig, RP
通讯作者：
Kraig, RP
DOI：
10.1097/00004647-199801000-00008
发表时间：
1998-01-01
影响因子：
6.3
作者：
Caggiano, AO;Kraig, RP
通讯作者：
Kraig, RP