Taking into account circadian rhythm when conducting experiments on animals

Abstract

Gumz ML. Taking into account circadian rhythm when conducting experiments on animals. Am J Physiol Renal Physiol 310: F454-F455, 2016. First published December 30, 2015 doi:10.1152/ajprenal.00549.2015.-Do your kidneys know what time it is? Mounting evidence from human studies and animal models strongly suggests that the answer to this question is yes. The time has come to start reporting the time of day at which renal physiology studies are performed. circadian rhythm; physiology; reproducibility; rigor DO YOUR KIDNEYS KNOW what time it is? Mounting evidence from human studies and animal models strongly suggests that the answer to this question is yes. Human studies dating back several decades have consistently demonstrated time-of-daydependent changes in glomerular filtration rate, renal electrolyte excretion, renal blood flow, and circulating levels of several hormones that act directly on the kidney, including aldosterone ( Fig. 1) (for review see Refs. 14 and 19). A new report suggests that these rhythms are evident in children and teenagers, in addition to adults (6). Animal data from several laboratories have established a role for the molecular clock in the regulation of blood pressure, renal electrolyte handling, fetal kidney development, glomerular filtration rate, and renal metabolism (reviewed in Refs. 2 and 13). Importantly, unbiased global transcriptomic studies also support a role for circadian rhythms in renal function; the kidney is second only to the liver in terms of the absolute number of mRNAs that oscillate with a significant circadian rhythm (20). Collectively, these studies support the concept that time is an important aspect of renal function. A logical consequence of this finding is that researchers should consider the time of day in experimental design and, subsequently, should report the time of day at which experiments are conducted.The timing of physiological function is controlled by the circadian clock. On a basic level, the core molecular clock comprises several transcription factors, including BMAL1, CLOCK, PER, and CRY, that regulate gene expression [for details on this mechanism, see an excellent review (10)]. These clock proteins are expressed in nearly every cell type and tissue that has been tested, and this mechanism underlying circadian rhythms is conserved from bread mold to humans (4). The term "circadian" comes from the Latin circa dia, meaning "about a day." Franz Halberg first coined this term in the 1950s to describe rhythmic physiological functions exhibiting a period of ϳ24 h (5). Together with Frederic Bartter and their colleagues, Halberg established that adrenocortical hormones, including cortisol and aldosterone, were produced with a circadian pattern (3, 7). Importantly, they demonstrated that these rhythms persisted, even under constant conditions, the defining characteristic for a process to be considered truly "circadian."The time of day at which physiological parameters are measured can affect the results of an experiment. One of the best examples of this...

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