Ontogeny of Circadian Organization in the Rat

Abstract

The mammalian circadian system is orchestrated by a master pacemaker in the brain but many peripheral tissues also contain independent or quasi-independent circadian oscillators. The adaptive significance of clocks in these structures must lie, in large part, in the phase relationships between the constituent oscillators and their micro-and macro-environments. To examine the relationship between postnatal development, which is dependent on endogenous programs and maternal/ environmental influences, and the phase of circadian oscillators, we assessed the circadian phase of pineal, liver, lung, adrenal, and thyroid tissues cultured from Period 1-luciferase (Per1-luc) rat pups of various postnatal ages. The liver, thyroid, and pineal were rhythmic at birth, but the phases of their Per1-luc expression rhythms shifted remarkably during development. To determine if the timing of the phase shift in each tissue could be the result of changing environmental conditions, we monitored the behavior of pups and their mothers. We found that the circadian phase of the liver shifted from the day to night around postnatal day (P) 22 as the pups nursed less during the light and instead ate solid food during the dark. Furthermore, the phase of Per1-luc expression in liver cultures from nursing neonates could be shifted experimentally from the day to the night by allowing pups access to the dam only during the dark. Peak Per1-luc expression also shifted from mid-day to early night in thyroid cultures at about P20, concurrent with the shift in eating times. The phase of Per1-luc expression in the pineal gland shifted from day to night coincident with its sympathetic innervation at around P5. Per1-luc expression was rhythmic in adrenal cultures and peaked around the time of lights-off throughout development, however, the amplitude of the rhythm increased at P25. Lung cultures were completely arrhythmic until P12 when the pups began to leave the nest. Taken together,

Time matters: pathological effects of repeated psychosocial stress during the active, but not inactive, phase of male mice

“…Intriguingly, the response of the SDD was even greater than that of the SHC mice at this timepoint, which supports our claim that these mice do not generate an adaptive ACTH insensitivity. Importantly, peripheral organs such as the adrenal glands show their intrinsic rhythm of clock gene expression (likely a measure of the rhythmicity of the tissue) for at least a few days after they had been removed from an animal, indicating that this process is not centrally regulated by the SCN (Yamazaki et al 2000(Yamazaki et al , 2009. Thus, the CORT secretion of adrenal explants during in vitro ACTH stimulation does not reflect the potential of the adrenal to secret CORT at the moment of killing, but at the actual stimulation period.…”

The Mammalian Circadian Timing System: Organization and Coordination of Central and Peripheral Clocks

“…Thus, in both SCN cells and peripheral cells, the rhythm-generating molecular circuitry is thought to be based on a delayed transcriptional/translational feedback loop (TTFL) involving essentially the same core clock components (see Reference 1). Intriguingly, cultured cells (106) and tissue explants from liver, lung, kidney, spleen, pancreas, heart, stomach, skeletal muscle, lung, cornea, thyroid gland, and adrenal gland exhibit robust circadian oscillations in gene expression (178,(180)(181)(182). In contrast, analysis of clock gene expression in mouse thymus and testis revealed somewhat conflicting results: One research group could not find cyclic mRNA accumulation, whereas another described a 12-h cycle for clock gene expression (183,184).…”

Endocrine regulation of circadian physiology

“…GR is ubiquitously expressed throughout the body, with the notable exception of the SCN (Okamura 2007). It exerts a plethora of physiological effects by binding to GC-responsive elements (GREs) in the promotor of target genes and upregulating their expression (Yamazaki et al 2009). The mechanism of GC-induced resetting of local clocks has been described.…”