Characterization of locomotor activity circadian rhythms in athymic nude mice

Abstract

BackgroundThe 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.MethodsGeneral 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.ResultsFree-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.ConclusionsSince 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.

Bioluminescent Multi-Characteristic Opsin for Simultaneous Optical Stimulation and Continuous Monitoring of Cortical Activities

“…To better characterize the network activity upon visual stimulation, neuronal activation parameter (NAP) was defined as a function of the number of nodes, the number of paths it connects, and the strength of Ca 2+ bioluminescence signal, although under anesthesia, a fourfold increase in NAP in the interval of the seventh to eighth recording hour (Figure 6N) is consistent with the earlier observation of increased activities during this period in non-anesthetized mice (Paladino et al, 2013;Lezak et al, 2017). Continuous EEG monitoring of the for 24 h (12-h light and 12-h dark) shows basal level of activity counts at the 1st-9th ZT hours, which increases significantly (∼5X) at the 11th-12th ZT hour and reaches minimum at ∼18th -19th ZT hour (Paladino et al, 2013;Lezak et al, 2017). Furthermore, our observation of decrease in Ca2 + bioluminescence activities after the 7th-8th until > 14th hour of recording matches well with the reported trend (Paladino et al, 2013;Lezak et al, 2017).…”

“…Continuous EEG monitoring of the for 24 h (12-h light and 12-h dark) shows basal level of activity counts at the 1st–9th ZT hours, which increases significantly (∼5X) at the 11th–12th ZT hour and reaches minimum at ∼18th –19th ZT hour ( Paladino et al, 2013 ; Lezak et al, 2017 ). Furthermore, our observation of decrease in Ca2 + bioluminescence activities after the 7th–8th until > 14th hour of recording matches well with the reported trend ( Paladino et al, 2013 ; Lezak et al, 2017 ). The autonomic response of the body due to circadian clock makes cortical neurons hyperactive with respect to visual stimulation, which is displayed in our extended Ca 2+ bioluminescence imaging.…”

“…This creates a tool that can report on internal cellular activities as a result of endogenous changes as well as induced changes from the cell-specific activation of the opsin. The uninterrupted recording of visually evoked neural activities in the cortex of mice enabled the determination of strength of sensory activation, which peaked at the seventh to eighth hour of anesthesia, coinciding with circadian rhythm ( Paladino et al, 2013 ; Lezak et al, 2017 ). For better quantification of network activities, we also employed an artificial intelligence-based decoding algorithm, which transforms the time-lapse Ca 2+ bioluminescence measurement peaks to a list of position coordinates and determines the communication pathway between them.…”

Impact of fasting on the rhythmic expression of myogenic and metabolic factors in skeletal muscle of adult mice

“…Apart from the food intake factor, physical activity might also directly influence gene expression and activation of signaling pathways. Locomotor activity in mice has a distinct circadian rhythm, with nocturnal activity accounting for ϳ70% of the total activity (39). In skeletal muscles of freely fed mice, MyoD, Myogenin, MuRF1, Fbxo32, Akt1, and S6 gene expression had a circadian pattern, with high expression during dark hours and low expression during light hours, and we do not exclude the possibility that higher nocturnal activity of mice may have affected expression of these genes.…”

Circadian Alterations in a Murine Model of Hypothalamic Glioma

“…Since pathologies affecting hypothalamic function can disrupt circadian timekeeping (Giustina and Braunstein, 2016 ), the presence of anomalous cells, such as glia-derived tumor cells could then modify circadian output clock, and be of relevance in the diagnosis of this tumors. Therefore, we aimed to study the effects of hypothalamic tumors on the circadian system, using an animal model suitable both for human tumor implantation and characterization of circadian parameters (Paladino et al, 2013 ).…”