Abstract
Fatigue is a very common and costly symptom associated with various diseases and disorders. Nonetheless, understanding the pathobiology and developing of therapies for fatigue have been difficult, partly because of a lack of consensus on the measures to phenotype this behavior, both in clinical settings and in animal studies. Here, we describe a fatigue-like behavior induced in mice by abdominal irradiation and compare three different methods of measuring changes in physical activity over time: running wheels, video home cage monitoring, and telemetry. These methods collect data passively and continuously, requiring no disruption of animals’ normal home cage behavior. In our experiments, all three methods reported a fatigue-like behavior, exhibited by a reduction in physical activity following abdominal irradiation. Video tracking showed the largest fatigue effect size (Cohen’s D = 1.78) over four days of monitoring, and was the only method showing a significant decrease in activity during the light period. Telemetry and running wheels showed a similar effect size (D = 1.68 and 1.65, respectively), but running wheels showed different circadian patterns of physical activity. In addition, we conducted rotarod and inverted grid suspension tests, which suggested that fatigue-like behavior was not the result of gross motor abnormalities.
Highlights
Fatigue is a common, bothersome symptom that has a very high negative impact on a person’s quality of life and significant repercussions on both direct and indirect health economic outcomes[1]
Much of the published work on mouse models of fatigue focuses on cancer-related fatigue, which can be induced by tumor growth[7,8,9,10], chemotherapy[10,11,12,13,14,15], or radiation[10,16,17]
The telemetry group began with 22 mice, but two died during the irradiation procedure and one was removed from the study due to health concerns
Summary
Bothersome symptom that has a very high negative impact on a person’s quality of life and significant repercussions on both direct and indirect health economic outcomes[1]. We induced a fatigue-like change in behavior using targeted abdominal irradiation, an animal model of fatigue developed to mimic localized radiation therapy for non-metastatic prostate cancer patients. We chose this model because (1) it is not caused by a specific disease, (2) it induces fatigue without causing any direct damage to the brain or other major organ systems, (3) it generates a trajectory of fatigue that resolves to baseline values, and (4) it can potentially be translated into a repeated stress model or an inflammatory model of fatigue. The methods tested did not require experimenter interaction with the mice nor did they disrupt the normal daily activity of the mice
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