Department of Biology, Utah State University, 4715 Old Main Hill, Logan, UT 84322, USA.
Physiol Behav. 2012 May 15;106(2):158-63. doi: 10.1016/j.physbeh.2012.01.024. Epub 2012 Feb 7.
We have previously shown that voluntary wheel running activity in mice is associated with an increase in the Endoplasmic Reticulum (ER) Unfolded Protein stress response in multiple regions of the brain. Mice that are given access to running wheels show large variations in individual running activity. In contrast, when food is placed on the lid of their cages, rather than within the cage, all mice must undertake significant physical activity in order to gain access to their food. Hence we investigated the effects of food location on food intake and growth of C57BL/6 mice and on the activity of the ER stress system in the brain as reflected in the expression of two marker genes, Xbp1 and Atf6. Mice that had food in cups within their cages and allowed access to running wheels showed the anticipated changes in food intake, body weight and ER stress in the hippocampus compared to mice with no access to running wheels. Locating the food on the lid had no effect on food intake but reduced weight gain significantly. Likewise, locating food on the lid increased the expression of both Xbp1 and Atf6 in the hippocampi in the absence of any running wheel activity. Voluntary wheel running activity was reduced in mice whose food was located on the cage lid and this running actually reduced the expression of the two marker ER stress genes. We conclude that the usual practice of providing food for mice on their cage lids provides a significant level of physical activity that alters the metabolic status and increases ER stress. As such, this may not be the optimal model for the majority of mouse studies that are reported in the literature and it may significantly alter the interpretation of the effect of wheel running activity on ER stress. The differential effects of food location on hippocampal Bdnf gene expression also suggest that BDNF does not directly regulate UPR activity but may be coordinately regulated in response to running activity.
我们之前的研究表明，在多种脑区中，小鼠的自愿轮跑活动与内质网（ER）未折叠蛋白应激反应的增加有关。给予轮跑机会的小鼠在个体跑活动量上存在较大差异。相比之下，当食物放在笼子的盖子上而不是笼子内时，所有老鼠都必须进行大量的体力活动才能吃到食物。因此，我们研究了食物位置对 C57BL/6 小鼠的食物摄入量和生长以及大脑中 ER 应激系统活性的影响，这反映在两个标记基因 Xbp1 和 Atf6 的表达上。与没有轮跑机会的小鼠相比，将食物放在笼子里的杯子里并允许轮跑的小鼠的食物摄入量、体重和海马体中的 ER 应激发生了预期的变化。将食物放在盖子上对食物摄入量没有影响，但显著减少了体重增加。同样，在没有任何轮跑活动的情况下，将食物放在盖子上会增加海马体中 Xbp1 和 Atf6 的表达。将食物放在笼子盖子上的老鼠的自愿轮跑活动减少，而这种跑步实际上降低了两个标记 ER 应激基因的表达。我们得出的结论是，将食物放在笼子盖子上的通常做法为老鼠提供了大量的体力活动，从而改变了代谢状态并增加了 ER 应激。因此，对于文献中报道的大多数老鼠研究来说，这可能不是最佳模型，它可能会显著改变对轮跑活动对 ER 应激影响的解释。食物位置对海马体 Bdnf 基因表达的不同影响也表明，BDNF 不会直接调节 UPR 活性，而是可能作为对跑步活动的协调反应进行调节。
