Hatanpää K, Brady D R, Stoll J, Rapoport S I, Chandrasekaran K
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892-1582, USA.
Ann Neurol. 1996 Sep;40(3):411-20. doi: 10.1002/ana.410400310.
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.
我们通过原位杂交检测细胞色素氧化酶亚基III信使核糖核酸（线粒体能量代谢的一个标志物），研究了阿尔茨海默病（AD）神经元的神经活动及其与神经原纤维缠结积累的关系。在AD颞中皮质，与无缠结的神经元相比，存在早期神经原纤维缠结的神经元中细胞色素氧化酶亚基III信使核糖核酸水平降低了26%（p < 0.01）。然而，同样由线粒体DNA编码的12S核糖体核糖核酸水平以及总信使核糖核酸水平仅在缠结发展的后期阶段降低。将4例AD脑的无缠结神经元与3例对照脑的无缠结神经元进行比较，发现AD无缠结神经元中细胞色素氧化酶亚基III信使核糖核酸水平低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，观察到的细胞色素氧化酶亚基III信使核糖核酸水平降低可能反映了AD中由于突触功能受损导致的下调。因此，突触传递失败可能先于缠结形成。随着缠结形成的进展，神经活动进一步下降。然而，这些结果也可以被视为表明在神经原纤维病理早期阶段神经元具有活力并持续活动，尽管水平较低。
