Micro-RNA abundance and stability in human brain: Specific alterations in Alzheimer's disease temporal lobe neocortex

Micro-RNA abundance and stability in human brain: Specific alterations in Alzheimer's disease temporal lobe neocortex
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DOI:
10.1016/j.neulet.2009.04.052
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发表时间:
2009-08-07
影响因子:
2.5
通讯作者:
Lukiw, Walter J.
Lukiw, Walter J.
中科院分区:
医学4区
文献类型:
--
作者:
Sethi, Prerna;Lukiw, Walter J.

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微RNA(micro-RNA,miRNA)介导的对中枢神经系统(CNS)信使RNA(messenger RNA,mRNA)复杂性的调控是CNS特异性基因在发育、可塑性、衰老和疾病过程中表达调控的关键因素。在这些研究中,基于miRNA阵列和北方印迹的对原代培养的人神经(HN)细胞和短死后间隔(PMI,类似于1小时)人脑组织中的特定miRNA丰度和衰变动力学的跟踪显示特定脑富集的miRNA的有限稳定性和相对短的半衰期(类似于1 - 3.5小时)。简而言之,在PMI阿尔茨海默病(AD)影响的颞叶新皮质中,发现miRNA-9,miRNA-125 b和miRNA-146 a显著上调,这在几种相关的神经系统疾病中没有观察到。结果表明(a)除非特别稳定,某些脑富集的miRNA代表使用CNS基因表达的高度瞬时效应物的快速执行的信号传导系统,和(B)在AD颞叶新皮质特异性脑miRNA在丰度上显著上调,并且与AD型神经病理学变化的存在强烈相关。出版社:Elsevier爱尔兰Ltd.
Micro-RNA (miRNA) mediated regulation of messenger RNA (mRNA) complexity in the central nervous system (CNS) is emerging as a critical factor in the control of CNS-specific gene expression during development, plasticity, aging and disease. In these studies, miRNA array and Northern blot based tracking of specific miRNA abundances and decay kinetics in human neural (HN) cells in primary culture and in short post-mortem interval (PMI, similar to 1 h) human brain tissues showed a limited stability and relatively short half-life (similar to 1 -3.5 h) for specific brain-enriched miRNAs. In short PMI Alzheimer's disease (AD)-affected temporal lobe neocortex, miRNA-9, miRNA-125b and miRNA-146a were found to be significantly up-regulated, an effect that was not seen in several related neurological disorders. The results suggest (a) that unless specifically stabilized, certain brain-enriched miRNAs represent a rapidly executed signaling system employing highly transient effectors of CNS gene expression, and (b) that in AD temporal lobe neocortex specific brain miRNAs are significantly up-regulated in abundance and strongly correlate with the presence of AD-type neuropatholgical change. Published by Elsevier Ireland Ltd.