Laboratorio Cajal de Circuitos Corticales (CTB) , Universidad Politécnica de Madrid , Campus Montegancedo , 28223 Pozuelo de Alarcón , Madrid , Spain.
Instituto Cajal (CSIC) , Avenida Doctor Arce 37 , 28002 Madrid , Spain.
J Proteome Res. 2019 Mar 1;18(3):1175-1190. doi: 10.1021/acs.jproteome.8b00816. Epub 2019 Jan 22.
Syrian hamsters undergo a reversible hyperphosphorylation of protein τ during hibernation, providing a unique natural model that may unveil the physiological mechanisms behind this critical process involved in the development of Alzheimer's disease and other tauopathies. The hibernation cycle of these animals fluctuates between a pair of stages: 3-4 days of torpor bouts interspersed with periods of euthermia called arousals that last several hours. In this study, we investigated for the first time the metabolic changes in brain tissue during hibernation. A total of 337 metabolites showed statistically significant differences during hibernation. Based on these metabolites, several pathways were found to be significantly regulated and, therefore, play a key role in the regulation of hibernation processes. The increase in the levels of ceramides containing more than 20 C atoms was found in torpor animals, reflecting a higher activity of CerS2 during hibernation, linked to neurofibrillary tangle generation and structural changes in the Golgi apparatus. Our results open up the debate about the possible significance of some metabolites during hibernation, which may possibly be related to τ phosphorylation and dephosphorylation events. In general, this study may provide insights into novel neuroprotective agents because the alterations described throughout the hibernation process are reversible.
叙利亚仓鼠在冬眠期间经历蛋白 tau 的可逆磷酸化，为研究阿尔茨海默病和其他 tau 病发展过程中涉及的这一关键生理机制提供了独特的天然模型。这些动物的冬眠周期在一对阶段之间波动：3-4 天的蛰伏期，其间穿插着称为觉醒的几个小时的常温期。在这项研究中，我们首次研究了冬眠期间脑组织的代谢变化。共有 337 种代谢物在冬眠期间表现出统计学上的显著差异。基于这些代谢物，发现有几个途径受到显著调节，因此在调节冬眠过程中发挥着关键作用。在蛰伏动物中发现含有 20 个以上碳原子的神经酰胺水平升高，反映了 CerS2 在冬眠期间的活性更高，与神经原纤维缠结的产生和高尔基器的结构变化有关。我们的研究结果引发了关于一些代谢物在冬眠期间可能具有重要意义的争论，这些代谢物可能与 tau 磷酸化和去磷酸化事件有关。总的来说，这项研究可能为新型神经保护剂提供思路，因为整个冬眠过程中描述的改变是可逆的。
