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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Alterations in mammalian target of rapamycin signaling pathways after traumatic brain injury.
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Alterations in mammalian target of rapamycin signaling pathways after traumatic brain injury.

机译：脑外伤后雷帕霉素信号转导途径的哺乳动物靶标改变。

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摘要

In response to traumatic brain injury (TBI), neurons initiate neuroplastic processes through the activation of intracellular signaling pathways. However, the molecular mechanisms underlying neuroplasticity after TBI are poorly understood. To study this, we utilized the fluid-percussion brain injury (FPI) model to investigate alterations in the mammalian target of rapamycin (mTOR) signaling pathways in response to TBI. Mammalian target of rapamycin stimulates mRNA translation through phosphorylation of eukaryotic initiation factor 4E binding protein-1 (4E-BP1), p70 ribosomal S6 kinase (p70S6K), and ribosomal protein S6 (rpS6). These pathways coordinate cell growth and neuroplasticity via dendritic protein synthesis. Rats received sham surgery or moderate parasagittal FPI on the right side of the parietal cortex, followed by 15 mins, 30 mins, 4 h, 24 h, or 72 h of recovery. Using Western blot analysis, we found that mTOR, p70S6K, rpS6, and 4E-BP1 phosphorylation levels were significantly increased in theipsilateral parietal cortex and hippocampus from 30 mins to 24 h after TBI, whereas total protein levels were unchanged. Using confocal microscopy to localize these changes, we found that rpS6 phosphorylation was increased in the parietal cortex and all subregions of the hippocampus. In accordance with these results, eIF4E, a key, rate-limiting mRNA translation factor, was also phosphorylated by mitogen-activated protein kinase-interacting kinase 1 (Mnk1) 15 mins after TBI. Together, these results suggest that changes in mRNA translation may be one mechanism that neurons use to respond to trauma and may contribute to the neuroplastic changes observed after TBI.
机译：响应创伤性脑损伤（TBI），神经元通过激活细胞内信号传导途径来启动神经增生过程。但是，对TBI后神经可塑性的分子机制了解甚少。为了对此进行研究，我们利用了液压冲击脑损伤（FPI）模型来研究雷帕霉素（mTOR）信号转导途径对TBI的哺乳动物靶点的改变。雷帕霉素的哺乳动物靶标通过真核起始因子4E结合蛋白1（4E-BP1），p70核糖体S6激酶（p70S6K）和核糖体蛋白S6（rpS6）的磷酸化刺激mRNA翻译。这些途径通过树突状蛋白质合成来协调细胞生长和神经可塑性。大鼠在顶叶皮层右侧接受假手术或中度矢状旁旁FPI，然后分别恢复15分钟，30分钟，4小时，24小时或72小时。使用蛋白质印迹分析，我们发现TBI后30分钟至24小时，同侧顶叶皮层和海马中的mTOR，p70S6K，rpS6和4E-BP1磷酸化水平显着增加，而总蛋白水平未改变。使用共聚焦显微镜定位这些变化，我们发现顶叶皮层和海马的所有子区域中的rpS6磷酸化增加。根据这些结果，eIF4E，一种关键的限速mRNA翻译因子，在TBI后15分钟也被促分裂原激活的蛋白激酶-相互作用激酶1（Mnk1）磷酸化。总之，这些结果表明，mRNA翻译的变化可能是神经元对创伤做出反应的一种机制，并且可能有助于TBI后观察到的神经塑性变化。

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