Neuronal activity and early neurofibrillary tangles in Alzheimer's disease
Neuronal activity and early neurofibrillary tangles in Alzheimer's disease
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DOI：
10.1002/ana.410400310
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发表时间：
1996-09-01
影响因子：
11.2
通讯作者：
Chandrasekaran, K
中科院分区：
文献类型：
--
作者：
Hatanpaa, K;Brady, DR;Chandrasekaran, K
我们研究了神经元的活动和它的关系，在阿尔茨海默氏病（AD）神经元的神经细胞色素氧化酶亚基III信使RNA，线粒体能量代谢的标志物，通过原位杂交神经元缠结的积累。在AD颞叶中皮层，细胞色素氧化酶亚基III信使RNA水平在早期神经元缠结的神经元中比无缠结的神经元降低了26%（p < 0.01）。然而，12S核糖体RNA，也编码的线粒体DNA，和总信使RNA的水平下降，只有在缠结发展的后期阶段。比较4个AD脑的无缠结神经元与3个对照脑的无缠结神经元，发现AD无缠结神经元中细胞色素氧化酶亚基III信使RNA的水平低25%（p < 0.001）。由于神经元的能量代谢需求主要由突触输入决定，因此观察到的细胞色素氧化酶亚基III信使RNA的减少可能反映了AD中突触功能受损所致的下调。因此，突触传递的失败可能先于缠结形成。随着缠结形成的进展，神经元活动进一步下降。然而，这些结果也可以被视为显示了神经元在神经病理学早期阶段的活力和持续活性，尽管水平较低。
We studied neuronal activity and its relation to the accumulation of neurofibrillary tangles in Alzheimer's disease (AD) neurons by in situ hybridization to cytochrome oxidase subunit III messenger RNA, a marker of mitochondrial energy metabolism. In AD midtemporal cortex, levels of cytochrome oxidase subunit III messenger RNA were decreased by 26% in neurons bearing early-stage neurofibrillary tangles as compared to tangle-free neurons (p < 0.01). However, levels of 12S ribosomal RNA, also encoded by mitochondrial DNA, and of total messenger RNA were decreased only in later stages of tangle development. Comparing tangle-free neurons of 4 AD brains to tangle-free neurons of 3 control brains, levels of cytochrome oxidase subunit III messenger RNA were found to be 25% lower (p < 0.001) in AD tangle-free neurons. Because energy metabolic needs of neurons are mainly determined by synaptic input, the observed decreases in cytochrome oxidase subunit III messenger RNA likely reflect downregulation due to impaired synaptic function in AD. Thus, a failure in synaptic transmission may precede tangle formation. A further decline in neuronal activity is seen as tangle formation progresses. However, these results can also be viewed as showing the viability and continuing activity, albeit at a lower level, of neurons in the early stages of neurofibrillary pathology.