Diurnal Corticosterone Presence and Phase Modulate Clock Gene Expression in the Male Rat Prefrontal Cortex.
Diurnal Corticosterone Presence and Phase Modulate Clock Gene Expression in the Male Rat Prefrontal Cortex.
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DOI：
10.1210/en.2015-1884
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发表时间：
2016-02
期刊：
影响因子：
4.8
通讯作者：
E. Woodruff;L. Chun;Laura R. Hinds;R. Spencer
中科院分区：
文献类型：
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作者：
E. Woodruff;L. Chun;Laura R. Hinds;R. Spencer
情绪障碍与前额皮质 (PFC) 功能、昼夜节律和昼夜糖皮质激素（皮质酮 [CORT]）循环失调有关。一些外周组织中时钟基因表达的夹带依赖于 CORT。在本研究中，我们表征了不同昼夜 CORT 条件下雄性大鼠 PFC 和视交叉上核 (SCN) 中核心时钟基因 Per1、Per2 和 Bmal1 的 mRNA 表达模式。在实验1中，大鼠的肾上腺保持完整（假手术）或肾上腺切除（ADX），然后每日10次反相（内源性CORT峰值的相反时间）腹膜内注射媒介物或2.5 mg/kg CORT。在实验2中，所有大鼠均接受ADX手术，随后每天注射13次媒介物或CORT，与内源性CORT峰值反相或同相。在假手术大鼠中，时钟基因 mRNA 水平在 PFC 和 SCN 中显示出昼夜表达模式，但两种结构之间的相位不同。 ADX 显着改变了 PFC 中的时钟基因表达模式。这种改变通过同相 CORT 治疗而正常化，而反相 CORT 治疗似乎消除了昼夜模式（Per1 和 Bmal1）或抑制/反转其相位（Per2）。 CORT 条件对 SCN 中时钟基因表达的影响非常小。这些实验表明，糖皮质激素昼夜节律生理学的一个重要组成部分需要 CORT 对 PFC 中分子钟的调节。因此，他们还指出了在与 CORT 循环异常相关的疾病中导致 PFC 功能破坏的可能机制。
Mood disorders are associated with dysregulation of prefrontal cortex (PFC) function, circadian rhythms, and diurnal glucocorticoid (corticosterone [CORT]) circulation. Entrainment of clock gene expression in some peripheral tissues depends on CORT. In this study, we characterized over the course of the day the mRNA expression pattern of the core clock genes Per1, Per2, and Bmal1 in the male rat PFC and suprachiasmatic nucleus (SCN) under different diurnal CORT conditions. In experiment 1, rats were left adrenal-intact (sham) or were adrenalectomized (ADX) followed by 10 daily antiphasic (opposite time of day of the endogenous CORT peak) ip injections of either vehicle or 2.5 mg/kg CORT. In experiment 2, all rats received ADX surgery followed by 13 daily injections of vehicle or CORT either antiphasic or in-phase with the endogenous CORT peak. In sham rats clock gene mRNA levels displayed a diurnal pattern of expression in the PFC and the SCN, but the phase differed between the 2 structures. ADX substantially altered clock gene expression patterns in the PFC. This alteration was normalized by in-phase CORT treatment, whereas antiphasic CORT treatment appears to have eliminated a diurnal pattern (Per1 and Bmal1) or dampened/inverted its phase (Per2). There was very little effect of CORT condition on clock gene expression in the SCN. These experiments suggest that an important component of glucocorticoid circadian physiology entails CORT regulation of the molecular clock in the PFC. Consequently, they also point to a possible mechanism that contributes to PFC disrupted function in disorders associated with abnormal CORT circulation.