Forced Desynchronization of Activity Rhythms in a Model of Chronic Jet Lag in Mice

• Autores: Casiraghi, Leandro Pablo; Oda, Gisele A.; Chiesa, Juan José; Friesen, W. Otto; Golombek, Diego Andres
• Año de publicación: 2012
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: CHRONIC JET LAG; CIRCADIAN DISRUPTION; ENTRAINMENT; LOCOMOTOR ACTIVITY RHYTHMS; MATHEMATICAL SIMULATIONS; OSCILLATOR MODEL; SHIFT WORK
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

We studied locomotor activity rhythms of C57/Bl6 mice under a chronic jet lag (CJL) protocol (ChrA6/2), which consisted of 6-hour phase advances of the light-dark schedule (LD) every 2 days. Through periodogram analysis, we found 2 components of the activity rhythm: a short-period component (21.01 ± 0.04 h) that was entrained by the LD schedule and a long-period component (24.68 ± 0.26 h). We developed a mathematical model comprising 2 coupled circadian oscillators that was tested experimentally with different CJL schedules. Our simulations suggested that under CJL, the system behaves as if it were under a zeitgeber with a period determined by (24-[phase shift size/days between shifts]). Desynchronization within the system arises according to whether this effective zeitgeber is inside or outside the range of entrainment of the oscillators. In this sense, ChrA6/2 is interpreted as a (24 - 6/2 = 21 h) zeitgeber, and simulations predicted the behavior of mice under other CJL schedules with an effective 21-hour zeitgeber. Animals studied under an asymmetric T = 21 h zeitgeber (carried out by a 3-hour shortening of every dark phase) showed 2 activity components as observed under ChrA6/2: an entrained short-period (21.01 ± 0.03 h) and a long-period component (23.93 ± 0.31 h). Internal desynchronization was lost when mice were subjected to 9-hour advances every 3 days, a possibility also contemplated by the simulations. Simulations also predicted that desynchronization should be less prevalent under delaying than under advancing CJL. Indeed, most mice subjected to 6-hour delay shifts every 2 days (an effective 27-hour zeitgeber) displayed a single entrained activity component (26.92 ± 0.11 h). Our results demonstrate that the disruption provoked by CJL schedules is not dependent on the phase-shift magnitude or the frequency of the shifts separately but on the combination of both, through its ratio and additionally on their absolute values. In this study, we present a novel model of forced desynchronization in mice under a specific CJL schedule; in addition, our model provides theoretical tools for the evaluation of circadian disruption under CJL conditions that are currently used in circadian research.
Fil: Casiraghi, Leandro Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Oda, Gisele A.. Universidade de Sao Paulo; Brasil
Fil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Friesen, W. Otto. University of Virginia; Estados Unidos
Fil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina