Name: a mouse model of fatigue induced by peripheral irradiation
Uploaded: 2017-03-17T14:00:00
Description: Watch this Scientific Journal Video about A Mouse Model of Fatigue Induced by Peripheral Irradiation at JoVE.com

The authors would like to thank Michele Allen of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) for generously sharing her expertise in murine phenotyping methods and for her ongoing technical assistance, as well as for Timothy Hunt of NHLBI for helping us develop the shielding device. This study is supported by the Division of Intramural Research of the National Institute of Nursing Research of the NIH, and part of the validation trial is supported by a grant from the Oncology Nursing Society Foundation.

Ethics Statement: This study was approved by the National Institutes of Health (NIH) Animal Care and Use Committee. All investigators taking part in animal handling and measurement of study outcomes were properly trained by the NIH Office of Animal Care and Use and the National Heart, Lung, and Blood Institute Murine Phenotyping Core. All aspects of animal testing, housing, and environmental conditions used in this study were in compliance with The Guide for the Care and Use of Laboratory Animals11</sup...

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We have described a protocol using targeted peripheral irradiation to induce a reduction of VWRA in mice without confounding morbidity or mortality. Importantly, a simple shielding device allows irradiation in this protocol to target a desired region consistently, mimicking the radiation treatments received by patients with pelvic cancer. In contrast to existing CRF models involving brain or total body irradiation8,9, this model explores how a peripherally-target...

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments1. The fatigue is neither proportional to recent activity nor alleviated by rest, and it is associated with a wide variety of disturbances related to mood, motivation, attention, and cognition2. The biological causes of CRF are unknown, though it has been shown in many cases to correlate with inflammation and cytokine levels, also in some cases with hemoglobin levels and the function of various hormone systems (see Saligan et al.3 for a review of biological studies of CRF).
Controlled studies using animal models are necessary to understand the behavior and biology associated with this complex condition. While tumor-related4 or chemotherapy-related5,6 fatigue has been studied in rodent models, the etiology of CRF may be treatment-specific. To investigate CRF related to radiation therapy, our group has recently developed a mouse model of irradiation-induced fatigue7. In contrast to existing CRF models involving brain or total body irradiation8,9, this model explores how a change in centrally-driven behavior, like fatigue, can be triggered by a peripherally-targeted irradiation procedure.
The procedure described here is designed to model radiation therapy administered to patients with pelvic cancer, using lead shielding to target the lower abdominal/pelvic region with irradiation. However, by modifying the lead shielding or its placement relative to experimental animals, this procedure could be adapted to model irradiation of other parts of the body. Voluntary wheel-running activity (VWRA) is used to measure fatigue-like behavior; because it&#39;s a voluntary and normal behavior10, it should allow the concurrent use of other behavioral and biological tests. We have found that peripheral irradiation is sufficient to reduce VWRA in mice without causing overt morbidity7. Future experiments with this model may help reveal effects of peripheral irradiation on immune and other biological signaling, as well as the downstream changes in the central nervous system that can produce deficits associated with CRF.

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a mouse model of fatigue induced by peripheral irradiation

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments, including radiation therapy. Here we describe a method using targeted peripheral irradiation to induce fatigue-like behavior in mice. With appropriate shielding, the irradiation targets the lower abdominal/pelvic region of the mouse, sparing the brain, in an effort to model radiation treatment received by individuals with pelvic cancers. We deliver an irradiation dose that is sufficient to induce fatigue-like behavior in mice, measured by voluntary wheel-running activity (VWRA), without causing obvious morbidity. Since wheel running is a normal, voluntary behavior in mice, its use should have little confounding effect on other behavioral tests or biological measures. Hence, wheel running can be used as a feasible outcome measure in understanding the behavioral and biological correlates of fatigue. CRF is a complex condition with frequent comorbidities, and likely has causes related both to cancer and its various treatments. The methods described in this paper are useful for investigating radiation-induced changes that contribute to the development of CRF and, more generally, to explore the biological networks that can explain the development and persistence of a peripherally-triggered but centrally-driven behavior like fatigue.

Three batches of mice were run through the protocol described above. There were a total of 16 sham and 20 irradiated (2,400 cGy, 3 x 800 cGy/day) mice. After three consecutive days of irradiation, the irradiated group showed significantly reduced VWRA compared to sham (mixed repeated measures ANOVA: main effect of irradiation treatment, F1,13 = 19.233, p &#60; 0.001). The effect was significant for the first seven days after irradiation (simple main effects, p &#60; 0.05 with B...

Watch this Scientific Journal Video about A Mouse Model of Fatigue Induced by Peripheral Irradiation at JoVE.com

A Mouse Model of Fatigue Induced by Peripheral Irradiation

We describe a method using targeted peripheral irradiation to induce fatigue-like behavior in mice. The selected non-lethal irradiation dose leads to a week-long reduction in voluntary wheel-running activity.

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments, including radiation therapy. ...

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