Department of Cell and Developmental Biology, University of Colorado School of Medicine, P.O. Box 6511, mail stop 8108, Aurora, CO 80045, USA.
J Comp Physiol B. 2010 Apr;180(4):599-617. doi: 10.1007/s00360-009-0422-9. Epub 2009 Dec 5.
During the torpor phase of mammalian hibernation when core body temperature is near 4 degrees C, the autonomic system continues to maintain respiration, blood pressure and heartbeat despite drastic reductions in brain activity. In addition, the hibernator's neuronal tissues enter into a protected state in which the potential for ischemia-reperfusion injury is markedly minimized. Evolutionary adaptations for continued function and neuroprotection throughout cycles of torpor and euthermia in winter are predicted to manifest themselves partly in changes in the brainstem proteome. Here, we compare the soluble brainstem protein complement from six summer active ground squirrels and six in the early torpor (ET) phase of hibernation. Thirteen percent of the approximately 1,500 quantifiable 2D gel spots alter significantly from summer to ET; the proteins identified in these differing spots are known to play roles in energy homeostasis via the tricarboxylic acid cycle (8 proteins), cytoarchitecture and cell motility (14 proteins), anabolic protein processes (13 proteins), redox control (11 proteins) and numerous other categories including protein catabolism, oxidative phosphorylation, signal transduction, glycolysis, intracellular protein trafficking and antiapoptotic function. These protein changes represent, at least in part, the molecular bases for restructuring of cells in the brainstem, a shift away from glucose as the primary fuel source for brain in the winter, and the generation of a streamlined mechanism capable of efficient and rapid energy production and utilization during the torpor and arousal cycles of hibernation.
在哺乳动物冬眠的蛰伏期,当核心体温接近 4 摄氏度时,自主神经系统尽管大脑活动明显减少,仍继续维持呼吸、血压和心跳。此外,冬眠动物的神经元组织进入一种保护状态,使缺血再灌注损伤的可能性明显降低。在冬季的蛰伏和正常体温循环中,持续功能和神经保护的进化适应预计会部分体现在脑干蛋白质组的变化上。在这里,我们比较了六只夏季活跃的地松鼠和六只处于早期蛰伏(ET)期的地松鼠的脑干可溶性蛋白质组。大约 1500 个可定量的 2D 凝胶点中有 13%从夏季到 ET 显著改变;这些不同点中鉴定出的蛋白质已知通过三羧酸循环(8 种蛋白质)、细胞结构和细胞运动(14 种蛋白质)、合成代谢蛋白过程(13 种蛋白质)、氧化还原控制(11 种蛋白质)以及许多其他类别,包括蛋白质分解代谢、氧化磷酸化、信号转导、糖酵解、细胞内蛋白质运输和抗凋亡功能,在能量稳态中发挥作用。这些蛋白质变化至少部分代表了脑干细胞结构重排的分子基础,即冬季大脑从葡萄糖作为主要燃料来源转变,以及产生一种能够在冬眠和觉醒循环中高效快速地产生和利用能量的简化机制。