Polyadenylated mRNA staining reveals distinct neuronal phenotypes following endothelin 1, focal brain ischemia, and global brain ischemia/ reperfusion.
Polyadenylated mRNA staining reveals distinct neuronal phenotypes following endothelin 1, focal brain ischemia, and global brain ischemia/ reperfusion.
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DOI：
10.1179/016164111x12881719352255
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发表时间：
2011-03
影响因子：
1.9
通讯作者：
DeGracia DJ
中科院分区：
文献类型：
--
作者：
Jamison JT;Lewis MK;Kreipke CW;Rafols JA;DeGracia DJ
大多数关于缺血诱导的神经元死亡的工作都围绕着坏死和凋亡的相对贡献，但这项工作还没有考虑到缺血诱导的应激反应的作用。一种扩展的观点认识到，在缺血诱导的神经元死亡的发生中，缺血诱导的损伤机制和应激反应之间存在竞争。脑缺血后应激反应的一个重要标志是神经元蛋白质合成受抑，与之相关的形态特征是核糖体外的信使核糖体以胞质信使核糖核酸颗粒的形式分裂。在这里，我们评估了在全脑缺血10分钟或15分钟再灌流1小时，单独局灶性脑缺血4小时，以及脑室注射内皮素-1后，这种mRNA颗粒反应的一般性。全脑和局灶性脑缺血均可引起皮层神经元胞浆中明显的mRNA颗粒形成。此外，我们报告了新的缺血后细胞表型，其特征是在内皮素1治疗和全脑缺血15分钟后，皮质神经元中的核多聚腺苷酸化的mRNA染色消失。在未缩小的缺血后神经元中，既有mRNA颗粒化，也有核mRNAs丢失。当细胞质中的mRNA颗粒通常显示为存活细胞的保护性反应时，核mRNAs的丢失可能标志着导致细胞萎缩/死亡的细胞损伤。因此，对总mRNA的染色可能揭示缺血后神经元早期应激反应和损伤机制之间的竞争方面。
Most work on ischemia-induced neuronal death has revolved around the relative contributions of necrosis and apoptosis, but this work has not accounted for the role of ischemia-induced stress responses. An expanded view recognizes a competition between ischemia-induced damage mechanisms and stress responses in the genesis of ischemia-induced neuronal death. An important marker of post-ischemic stress responses is inhibition of neuronal protein synthesis, a morphological correlate of which is the compartmentalization of mRNA away from ribosomes in the form of cytoplasmic mRNA granules. Here we assessed the generality of this mRNA granule response following either 10 or 15 minutes global brain ischemia and 1 hour reperfusion, 4 hours focal cerebral ischemia alone, and endothelin 1 intraventricular injection. Both global and focal ischemia led to prominent neuronal cytoplasmic mRNA granule formation in layer II cortical neurons. In addition, we report here new post-ischemic cellular phenotypes characterized by the loss of nuclear polyadenylated mRNA staining in cortical neurons following endothelin 1 treatment and 15 minutes global ischemia. Both mRNA granulation and loss of nuclear mRNAs occurred in non-shrunken post-ischemic neurons. Where cytoplasmic mRNA granules generally appear to mark a protective response in surviving cells, loss of nuclear mRNAs may mark cellular damage leading to cell atrophy/death. Hence, staining for total mRNA may reveal facets of the competition between stress responses and damage mechanisms at early stages in post-ischemic neurons.