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Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents
Published on: January 24, 2013
Characterization of locomotor activity circadian rhythms in athymic nude mice
Natalia Paladino1, José M Duhart, Malena L Mul Fedele
1Laboratorio de Cronobiología, Universidad Nacional de Quilmes, Nacional de Quilmes, R, S, Peña 180, Bernal, Buenos Aires, 1876, Argentina. dgolombek@unq.edu.ar.
Background:
The relation between circadian dysregulation and cancer incidence and progression has become a topic of major interest over the last decade. Also, circadian timing has gained attention regarding the use of chronopharmacology-based therapeutics. Given its lack of functional T lymphocytes, due to a failure in thymus development, mice carrying the Foxn1(Δ/Δ) mutation (nude mice) have been traditionally used in studies including implantation of xenogeneic tumors. Since the immune system is able to modulate the circadian clock, we investigated if there were alterations in the circadian system of the athymic mutant mice.
Methods:
General activity circadian rhythms in 2-4 month-old Foxn1(Δ/Δ) mice (from Swiss Webster background) and their corresponding wild type (WT) controls was recorded. The response of the circadian system to different manipulations (constant darkness, light pulses and shifts in the light-dark schedule) was analyzed.
Results:
Free-running periods of athymic mice and their wild type counterpart were 23.86 ± 0.03 and 23.88 ± 0.05 hours, respectively. Both strains showed similar phase delays in response to 10 or 120 minutes light pulses applied in the early subjective night and did not differ in the number of c-Fos-expressing cells in the suprachiasmatic nuclei, after a light pulse at circadian time (CT) 15. Similarly, the two groups showed no significant difference in the time needed for resynchronization after 6-hour delays or advances in the light-dark schedule. The proportion of diurnal activity, phase-angle with the zeitgeber, subjective night duration and other activity patterns were similar between the groups.
Conclusions:
Since athymic Foxn1(Δ/Δ) mice presented no differences with the WT controls in the response of the circadian system to the experimental manipulations performed in this work, we conclude that they represent a good model in studies that combine xenograft implants with either alteration of the circadian schedules or chronopharmacological approaches to therapeutics.
Insights
Athymic nude mice show normal circadian rhythms and responses to light manipulations, similar to wild-type controls. These findings support their use in xenograft studies involving circadian disruption or chronopharmacology.
Area of Science:
- Chronobiology
- Immunology
- Cancer Research
Background:
- Circadian dysregulation is linked to cancer incidence and progression.
- Chronopharmacology utilizes circadian timing for therapeutics.
- Athymic Foxn1(Δ/Δ) mice (nude mice) lack T lymphocytes and are used for xenograft studies.
- The immune system can influence the circadian clock, prompting investigation into nude mice's circadian system.
Purpose of the Study:
- To investigate potential alterations in the circadian system of athymic Foxn1(Δ/Δ) mice.
- To assess the suitability of nude mice for research combining xenograft models with circadian manipulations.
Main Methods:
- General activity circadian rhythms were recorded in nude mice and wild-type (WT) controls.
- The response of the circadian system to constant darkness, light pulses, and light-dark schedule shifts was analyzed.
Main Results:
- Nude mice and WT controls exhibited similar free-running periods (approx. 23.9 hours).
- Both groups showed comparable phase delays to light pulses and similar c-Fos expression in the suprachiasmatic nuclei.
- Resynchronization times after light-dark schedule shifts and activity patterns were not significantly different between the groups.
Conclusions:
- Athymic Foxn1(Δ/Δ) mice display no significant differences in circadian system responses compared to WT controls.
- These mice are a suitable model for xenograft studies involving circadian schedule alterations or chronopharmacological treatments.
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