Diverse development and higher sensitivity of the circadian clocks to changes in maternal-feeding regime in a rat model of cardio-metabolic disease.

Spontaneously hypertensive rats (SHR) develop cardiovascular and metabolic pathology in adulthood when their circadian system exhibits significant aberrances compared with healthy control rats. This study was aimed to elucidate how the SHR circadian system develops during ontogenesis and to assess its sensitivity to changes in maternal-feeding regime. Analysis of ontogenesis of clock gene expression rhythms in the suprachiasmatic nuclei, liver and colon revealed significant differences in SHR compared with Wistar rats. In the suprachiasmatic nuclei of the hypothalamus (SCN) and liver, the development of a high-amplitude expression rhythm selectively for Bmal1 was delayed compared with Wistar rat. The atypical development of the SHR circadian clocks during postnatal ontogenesis might arise from differences in maternal behavior between SHR and Wistar rats that were detected soon after delivery. It may also arise from higher sensitivity of the circadian clocks in the SHR SCN, liver and colon to maternal behavior related to changes in the feeding regime because in contrast to Wistar rat, the SHR SCN and peripheral clocks during the prenatal period and the hepatic clock during the early postnatal period were phase shifted due to exposure of mothers to a restricted feeding regime. The maternal restricted feeding regime shifted the clocks despite the fact that the mothers were maintained under the light/dark cycle. Our findings of the diverse development and higher sensitivity of the developing circadian system of SHR to maternal cues might result from previously demonstrated differences in the SHR circadian genotype and may potentially contribute to cardiovascular and metabolic diseases, which the animal model spontaneously develops.

Development and entrainment of the colonic circadian clock during ontogenesis.

Colonic morphology and function change significantly during ontogenesis. In mammals, many colonic physiological functions are temporally controlled by the circadian clock in the colon, which is entrained by the central circadian clock in the suprachiasmatic nuclei (SCN). The aim of this present study was to ascertain when and how the circadian clock in the colon develops during the perinatal period and whether maternal cues and/or the developing pup SCN may influence the ontogenesis of the colonic clock. Daily profiles of clock genes Per1, Per2, Cry1, Cry2, Rev-erbα, Bmal1, and Clock expression in the colon underwent significant modifications since embryonic day 20 (E20) through postnatal days (P) 2, 10, 20, and 30 via changes in the mutual phasing among the individual clock gene expression rhythms, their relative phasing to the light-dark regime, and their amplitudes. An adult-like state was achieved around P20. The foster study revealed that during the prenatal period, the maternal circadian phase may partially modulate development of the colonic clock. Postnatally, the absence and/or presence of rhythmic maternal care affected the phasing of the clock gene expression profiles in pups at P10 and P20. A reversal in the colonic clock phase between P10 and P20 occurred in the absence of rhythmic signals from the pup SCN. The data demonstrate ontogenetic maturation of the colonic clock and stress the importance of prenatal and postnatal maternal rhythmic signals for its development. These data may contribute to the understanding of colonic function-related diseases in newborn children.