Lopez Mary S, Dempsey Robert J, Vemuganti Raghu
Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA Cellular & Molecular Pathology Training Program, University of Wisconsin, Madison, WI, USA.
Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA Neuroscience Training Program, University of Wisconsin, Madison, WI, USA.
J Cereb Blood Flow Metab. 2016 Sep;36(9):1644-50. doi: 10.1177/0271678X16656202. Epub 2016 Jun 20.
The health benefits of the plant-derived polyphenol resveratrol were established in multiple disease systems. Notably, pre-treatment with resveratrol was shown to be neuroprotective in several models of cerebral ischemia. Mechanisms of resveratrol-mediated neuroprotection have been explored in the context of canonical resveratrol targets, but epigenetic and non-coding RNA processes have not yet been evaluated. Resveratrol was shown to alter microRNAs in cancer and cardiac ischemia. Previous studies also showed that ischemic preconditioning that induces ischemic tolerance significantly alters cerebral microRNA levels, particularly those that target neuroprotective pathways. Therefore, we tested if resveratrol-mediated ischemic tolerance also alters microRNA expression with a goal to identify microRNAs that are amenable to manipulation to induce neuroprotection after cerebral ischemia. Hence, we tested the microRNA profiles in mouse brain following intraperitoneal administration of resveratrol that induced significant tolerance against transient focal ischemia. We analyzed microRNA profiles using microarrays from both Affymetrix and LC Sciences that contain probes for all known mouse microRNAs. The results show that there is no consistent change in any of the microRNAs tested between resveratrol and vehicle groups indicating that microRNAs play a minimal role in resveratrol-mediated cerebral ischemic tolerance.
植物源多酚白藜芦醇对健康的益处已在多种疾病系统中得到证实。值得注意的是，在几种脑缺血模型中，白藜芦醇预处理显示出神经保护作用。白藜芦醇介导的神经保护机制已在经典白藜芦醇靶点的背景下进行了探索，但表观遗传和非编码RNA过程尚未得到评估。白藜芦醇已被证明可改变癌症和心脏缺血中的微小RNA。先前的研究还表明，诱导缺血耐受的缺血预处理会显著改变脑微小RNA水平，特别是那些靶向神经保护途径的微小RNA。因此，我们测试了白藜芦醇介导的缺血耐受是否也会改变微小RNA表达，目的是识别那些可通过调控来诱导脑缺血后神经保护的微小RNA。因此，我们在腹腔注射白藜芦醇诱导对短暂性局灶性缺血产生显著耐受后，检测了小鼠大脑中的微小RNA谱。我们使用来自Affymetrix和LC Sciences的微阵列分析微小RNA谱，这些微阵列包含针对所有已知小鼠微小RNA的探针。结果表明，在白藜芦醇组和对照组之间，所检测的任何微小RNA均无一致变化，这表明微小RNA在白藜芦醇介导的脑缺血耐受中作用极小。
