Circadian and photic regulation of clock and clock‐controlled proteins in the suprachiasmatic nuclei of calorie‐restricted mice

Abstract

In mammals, behavioural and physiological rhythms as well as clock gene expression in the central suprachiasmatic clock (SCN) are phase-shifted by a timed calorie restriction (T-CR; animals receiving at midday 66% of their daily food intake). The molecular mechanism of SCN depends on feedback loops involving clock genes and their protein products. To understand how T-CR mediates its synchronizing effects, we examined the rhythmic expression of three clock proteins, PERIOD (PER) 1, 2 and CLOCK, and one clock-controlled protein (i.e. vasopressin; AVP) in the SCN of mice either fed ad libitum (AL) or with T-CR. Moreover, we evaluated expression of these proteins in the SCN of AL and T-CR mice following a 1-h light pulse. The results indicate that, while PER1 and AVP rhythms were phase-advanced in T-CR mice, the PER2 rhythm showed an increased amplitude. CLOCK was expressed constitutively in AL mice while in T-CR it was significantly reduced, especially after feeding time. A light pulse produced a delayed increase in PER1 and a larger increase in PER2 expression in the SCN of T-CR mice than in AL animals. In addition, light exposure triggered an increase in AVP-ir cells in both AL and T-CR mice, and also of CLOCK expression but in T-CR mice only. The circadian changes in clock and clock-controlled proteins and their acute responses to light in the SCN of T-CR mice demonstrate that metabolic cues induced by a calorie restriction modulate the translational regulation of the SCN clock.

The Cerebellum Harbors a Circadian Oscillator Involved in Food Anticipation

“…Daynight expression of Bmal1 in the cerebellum of mice fed ad libitum is high and low at midday and midnight, respectively (C. Graff and E. Challet, unpublished data), as already observed (Namihira et al, 1999) and in accordance with its role as a transcriptional activator of Rev-erb␣ and Per genes. The daily expression of PER2 was delayed by ϳ5 h compared with the cycling of Per2, in keeping with the 4 -6 h lag found in the suprachiasmatic nuclei (Field et al, 2000;Mendoza et al, 2007). Moreover, immunohistochemical staining indicates that the cerebellar oscillator likely resides in the Purkinje cells.…”

Perinatal nutrient restriction induces long-lasting alterations in the circadian expression pattern of genes regulating food intake and energy metabolism

“…[22][23][24][25] Yet, the rythmicity of the circadian clock in the SCN is also disrupted if in addition to limiting the access to food the amount of calories is reduced to 60-70% in relation to animals fed ad libitum. [59][60][61] We observed that perinatal protein restriction altered in the long term, the circadian rhythmic characteristics of FAS, GCK and the clock core genes CLOCK, Bmal1 and Per1 in the liver indicating that the rythmicity of this peripheral clock is disrupted by early undernutrition. We also observed alterations in the circadian expression profile and/or the peak expression levels of NPY, AgRP, CART, Bmal1 and Per1 in the hypothalamus.…”

Forebrain oscillators ticking with different clock hands

“…Schematic sagittal section of a mouse forebrain summarizing differential PER1 (orange) and PER2 (purple) immunoreactivity (IR) under food ad libitum and respective modifications in response to hypocaloric feeding. aPirC: anterior piriform cortex, Arc: arcuate nuclei of the hypothalamus, BLA: basolateral amygdala, CA1: Ammon's horn, CEA: central amygdala, DG: dentate gyrus, DMH: dorsomedial nuclei of the hypothalamus, dST: dorsal striatum, PVN: paraventricular nuclei of the hypothalamus, PVT: paraventricular nucleus of the thalamus, SCN: suprachiasmatic nuclei (data analyzed in Mendoza et al, 2007), VMH: ventromedial nuclei of the hypothalamus.…”

“…PER2 expression has also been reported in limbic structures, such as amygdala and bed nucleus of the stria terminalis (Amir et al, 2004;Lamont et al, 2005). Except for the SCN in which the rhythm of PERs follows the mRNA expression by 4-6 h (Field et al, 2000;Mendoza et al, 2007), little is known about the exact timing of both PER1 and PER2 oscillations in forebrain structures. For that purpose, we investigated the daily patterns of PER1 and PER2 expression throughout the forebrain in mice fed ad libitum.…”