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雄性大鼠肾上腺生物钟基因昼夜节律表达及皮质酮节律的产后个体发育

Postnatal Ontogeny of the Circadian Expression of the Adrenal Clock Genes and Corticosterone Rhythm in Male Rats.

作者信息

Roa Silvia Liliana Ruiz, Martinez Edson Zangiacomi, Martins Clarissa Silva, Antonini Sonir Rauber, de Castro Margaret, Moreira Ayrton Custódio

机构信息

Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP 14049-900, Brazil.

Department of Social Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP 14049-900, Brazil.

出版信息

Endocrinology. 2017 May 1;158(5):1339-1346. doi: 10.1210/en.2016-1782.

Abstract

The postnatal synchronization of the circadian variation of the adrenal clock genes in mammals remains unknown. We evaluated the postnatal ontogeny of daily variation of clock genes (Clock/Bmal1/Per1/Per2/Per3/Cry1/Cry2/Rorα/Rev-Erbα) and steroidogenesis-related genes (Star and Mc2r) in rat adrenals and its relationship with the emergence of plasma corticosterone rhythm using cosinor analysis. Plasma corticosterone circadian rhythm was detected from postnatal day (P)1, with morning acrophase, between zeitgeber time (ZT)0 and ZT2. From P14, there was a nocturnal acrophase of corticosterone at ZT20, which was associated with pups' eye opening. From P3 there was a circadian variation of the mRNA expression of Bmal1, Per2, Per3, and Cry1 genes with morning acrophase, whereas Rev-Erbα had nocturnal acrophase. From P14, Bmal1, Per2, Per3, and Cry1 acrophases advanced by approximately 10 hours, as compared with early neonatal days, becoming vespertine-nocturnal. In all postnatal ages, Per2 and Cry1 circadian profiles were synchronized in phase with the circadian rhythm of plasma corticosterone, whereas Bmal1 was in antiphase. An adult-like Star circadian rhythm profile was observed only from P21. In conclusion, our original data demonstrated a progressive postnatal maturation of the circadian variation of the adrenal clock genes in synchrony with the development of the corticosterone circadian rhythm in rats.

摘要

哺乳动物肾上腺生物钟基因昼夜节律变化的产后同步性尚不清楚。我们使用余弦分析评估了大鼠肾上腺中生物钟基因(Clock/Bmal1/Per1/Per2/Per3/Cry1/Cry2/Rorα/Rev-Erbα)和类固醇生成相关基因(Star和Mc2r)的产后个体发育及其每日变化与血浆皮质酮节律出现的关系。从出生后第(P)1天开始检测到血浆皮质酮昼夜节律,其峰值出现在上午,在授时时间(ZT)0和ZT2之间。从P14开始,皮质酮的峰值出现在夜间ZT20,这与幼崽睁眼有关。从P3开始,Bmal1、Per2、Per3和Cry1基因的mRNA表达出现昼夜变化,峰值出现在上午,而Rev-Erbα的峰值出现在夜间。与新生儿早期相比,从P14开始,Bmal1、Per2、Per3和Cry1的峰值提前了约10小时,变为傍晚至夜间。在所有出生后年龄段,Per2和Cry1的昼夜节律与血浆皮质酮的昼夜节律同步,而Bmal1则相反。仅从P21开始观察到类似成年的Star昼夜节律模式。总之,我们的原始数据表明,大鼠肾上腺生物钟基因的昼夜变化在产后逐渐成熟,并与皮质酮昼夜节律的发展同步。

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