Dendritic BC200 RNA in aging and in Alzheimer's disease
Dendritic BC200 RNA in aging and in Alzheimer's disease
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DOI：
10.1073/pnas.0701532104
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发表时间：
2007-06-19
影响因子：
11.1
通讯作者：
Tiedge, Henri
中科院分区：
文献类型：
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作者：
Mus, El;Hof, Patrick R.;Tiedge, Henri
小的非翻译 BC1 和 BC200 RNA 是选择性靶向神经元体树突结构域的翻译调节因子。它们被认为是突触后树突微域中局部蛋白质合成的调节剂，有助于维持长期突触可塑性。由于可塑性失败被认为是阿尔茨海默病 (AD) 中神经退行性变化的起点，因此我们想知道 AD 大脑中人类 BC200 RNA 的体细胞树突水平是否失调。我们发现，在正常衰老过程中，49 岁至 86 岁之间，皮质区域的 BC200 水平降低了 60% 以上。相反，与年龄匹配的正常大脑相比，AD 大脑中的 BC200 RNA 显着上调。 AD 中的这种上调是与该疾病有关的大脑区域特有的。正如临床痴呆评分所反映的那样，这些区域的相对 BC200 水平随着 AD 的进展而增加。在疾病的更晚期阶段，BC200 RNA通常呈现成簇的核周定位，表明树突损失伴随着体细胞过度表达。 BC200 RNA 的错误定位和过度表达可能是 AD 神经元突触树突退化的反应补偿性或原因。
Small untranslated BC1 and BC200 RNAs are translational regulators that are selectively targeted to somatodendritic domains of neurons. They are thought to operate as modulators of local protein synthesis in postsynaptic dendritic microdomains, in a capacity in which they would contribute to the maintenance of long-term synaptic plasticity. Because plasticity failure has been proposed to be a starting point for the neurodegenerative changes that are seen in Alzheimer's disease (AD), we asked whether somatodendritic levels of human BC200 RNA are deregulated in AD brains. We found that in normal aging, BC200 levels in cortical areas were reduced by > 60% between the ages of 49 and 86. In contrast, BC200 RNA was significantly up-regulated in AD brains, in comparison with age-matched normal brains. This up-regulation in AD was specific to brain areas that are involved in the disease. Relative BC200 levels in those areas increased in parallel with the progression of AD, as reflected by Clinical Dementia Rating scores. in more advanced stages of the disease, BC200 RNA often assumed a clustered perikaryal localization, indicating that dendritic loss is accompanied by somatic overexpression. Mislocalization and overexpression of BC200 RNA may be reactive- compensatory to, or causative of, synaptodendritic deterioration in AD neurons.