Diverse development and higher sensitivity of the circadian clocks to changes in maternal-feeding regime in a rat model of cardio-metabolic disease
Diverse development and higher sensitivity of the circadian clocks to changes in maternal-feeding regime in a rat model of cardio-metabolic disease
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DOI：
10.3109/07420528.2015.1014095
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发表时间：
2015-05-01
影响因子：
2.8
通讯作者：
Sumova, Alena
中科院分区：
文献类型：
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作者：
Olejnikova, Lucie;Polidarova, Lenka;Sumova, Alena
自发性高血压大鼠（SHR）在成年期发生心血管和代谢病变，与健康对照大鼠相比，其昼夜节律系统表现出显着的异常。本研究旨在阐明SHR个体发育过程中昼夜节律系统的发育，并评估其对母体喂养制度变化的敏感性。分析个体发育的时钟基因表达节律在视交叉上核，肝脏和结肠显示显着差异，SHR与Wistar大鼠相比。在视交叉上核的下丘脑（SCN）和肝脏，发展的高振幅的表达节奏选择性Bmal 1相比，Wistar大鼠延迟。出生后个体发育过程中SHR昼夜节律钟的非典型发育可能源于SHR和Wistar大鼠分娩后不久检测到的母体行为差异。这也可能是由于SHR SCN、肝脏和结肠中的昼夜节律钟对与喂养方案变化相关的母体行为的更高敏感性引起的，因为与Wistar大鼠相反，由于母体暴露于限制性喂养方案，SHR SCN和产前期间的外周时钟以及出生后早期期间的肝脏时钟发生了相移。母亲限制喂养制度改变了时钟，尽管事实上，母亲保持在光/暗周期。我们的研究结果表明，SHR的昼夜节律系统对母体线索的多样性发展和更高的敏感性可能是由于先前证明的SHR昼夜节律基因型的差异，并可能导致动物模型自发发展的心血管和代谢疾病。
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.