Reversible paired helical filament-like phosphorylation of tau is an adaptive process associated with neuronal plasticity in hibernating animals
Reversible paired helical filament-like phosphorylation of tau is an adaptive process associated with neuronal plasticity in hibernating animals
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DOI：
10.1523/jneurosci.23-18-06972.2003
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发表时间：
2003-08-06
影响因子：
5.3
通讯作者：
Härtig, W
中科院分区：
文献类型：
--
作者：
Arendt, T;Stieler, J;Härtig, W
由过度磷酸化形式的微管相关蛋白tau形成的神经病理学[成对螺旋丝（PHF）]是阿尔茨海默病和相关病症的主要标志。tau蛋白磷酸化的过程，被认为是至关重要的PHF的形成，其潜在的联系，然而，并没有很好地理解，主要是因为缺乏一个生理学的PHF样tau蛋白磷酸化的体内模型。在这里，我们描述了高度磷酸化的tau蛋白的形成，含有一些PHF样表位在冬眠期间的麻木。tau蛋白的PHF样磷酸化与纤维形成无关，并且在唤醒后完全可逆。PHF样tau蛋白的分布遵循一致的模式，在内嗅皮质、海马和等皮质区最强烈。在海马内，在CA3锥体细胞中观察到特别高的标记。CA1区神经元的反应性稍低，而齿状回颗粒细胞则无反应。CA3神经元中PHF样tau蛋白的形成被终止于CA3顶树突的苔藓纤维系统的突触接触的消退所抑制。苔藓纤维传入在觉醒过程中重新建立，伴随着CA3神经元中PHF样tau蛋白的减少。这些发现暗示了神经元可塑性和PHF样tau蛋白磷酸化之间的重要联系。因此，PHF样tau蛋白的重复形成和降解可能代表一种不一定与病理效应相关的生理机制。因此，冬眠将是一个有价值的模型来研究PHF样tau磷酸化的调节及其在生理体内条件下的细胞生物学后遗症。
Neurofibrillary pathology [ paired helical filaments (PHFs)] formed by the microtubule-associated protein tau in a hyperphosphorylated form is a major hallmark of Alzheimer's disease and related disorders. The process of tau phosphorylation, thought to be of critical importance for PHF formation, and its potential link to neurodegeneration, however, is not understood very well, mostly because of the lack of a physiological in vivo model of PHF-like tau phosphorylation. Here we describe the formation of highly phosphorylated tau, containing a number of PHF-like epitopes in torpor during hibernation. PHF-like phosphorylation of tau was not associated with fibril formation and was fully reversible after arousal. Distribution of PHF-like tau followed a consistent pattern, being most intense in the entorhinal cortex, hippocampus, and isocortical areas. Within the hippocampus, a particularly high labeling was seen in CA3 pyramidal cells. Somewhat lesser reactivity was present in CA1 neurons while dentate gyrus granule cells were not reactive. Formation of PHF-like tau in CA3 neurons was paralleled by the regression of synaptic contacts of the mossy fiber system terminating on CA3 apical dendrites. Mossy fiber afferentation was re-established during arousal, concomitantly with the decrease of PHF-like tau in CA3 neurons.These findings implicate an essential link between neuronal plasticity and PHF-like phosphorylation of tau. The repeated formation and degradation of PHF-like tau might, thus, represent a physiological mechanism not necessarily associated with pathological effects. Hibernation will, therefore, be a valuable model to study the regulation of PHF-like tau-phosphorylation and its cell biological sequelae under physiological in vivo conditions.