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

摘要

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 maternalfeeding 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.