Induction of torpor in response to a common chronic food restriction paradigm: implications for behavioural research using mice

Sian L. Wilcox, D. Bannerman, S. Peirson, V. Vyazovskiy
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引用次数: 1

Abstract

Background Many behavioural, pharmacological, and metabolic studies in mice require fasting, yet the possibility of fasting-induced torpor affecting data is rarely considered. Torpor is a state characterised by depressed metabolism and profound alterations in physiology and behaviour. In this study, we aimed to determine whether a chronic food restriction paradigm, common in behavioural studies, was sufficient to induce torpor in mice. Methods Mice were food restricted to ~85-90% of their bodyweight, as is typically done, and monitored using continuous thermal imaging. Results We observed that body temperature significantly decreased over days of food restriction, and it was significantly related to the drop in bodyweight (r2=0.8989, p<0.0001). All mice reliably entered torpor daily from day 8 of food restriction which coincided with bodyweight stabilisation at ~85%. We found a strong positive relationship between the magnitude of the decrease of bodyweight and the proportion of mice entering torpor each day (r2=0.8715, p<0.0001). Conclusions Overall, we found that torpor is readily induced in response to food restriction. Considering that hunger is frequently used as a motivational drive in behavioural tasks, it is likely that torpor occurrence is common in such studies, while remaining undetected and unaccounted for. Due to the profound effect of torpor on physiology, it is possible that torpor induction may be confounding subsequent data and represents an important source of variation. We recommend that body temperature is always monitored noninvasively in studies where food restriction is employed, to determine when torpor is occurring, and that torpor history is appropriately controlled for within and across experimental groups.
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针对常见的慢性食物限制范例诱导倦怠:对使用小鼠进行行为研究的影响
背景 许多小鼠行为学、药理学和新陈代谢研究都需要禁食,但却很少考虑禁食引起的冬眠对数据产生影响的可能性。静止状态的特点是新陈代谢低下以及生理和行为的深刻改变。在这项研究中,我们旨在确定行为学研究中常见的慢性食物限制范式是否足以诱导小鼠的冬眠。方法 按照通常的方法,将小鼠的食物限制在其体重的约 85-90% 的范围内,并使用连续热成像对其进行监测。结果 我们观察到,体温在食物限制的几天内明显下降,而且与体重下降有显著关系(r2=0.8989,p<0.0001)。所有小鼠从限食的第 8 天开始每天都能可靠地进入冬眠状态,这与体重稳定在约 85% 的时间相吻合。我们发现体重下降的幅度与每天进入冬眠的小鼠比例之间存在很强的正相关关系(r2=0.8715,p<0.0001)。结论 总体而言,我们发现食物限制很容易诱导小鼠进入冬眠状态。考虑到饥饿经常被用作行为任务的动机驱动力,在此类研究中发生冬眠的情况很可能很常见,但仍未被发现和解释。由于暂时休眠对生理机能的深远影响,暂时休眠诱导可能会对后续数据造成混淆,并成为变异的一个重要来源。我们建议,在采用食物限制的研究中,应始终对体温进行无创监测,以确定冬眠何时发生,并对实验组内和实验组间的冬眠历史进行适当控制。
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