Variations in Phase and Amplitude of Rhythmic Clock Gene Expression across Prefrontal Cortex, Hippocampus, Amygdala, and Hypothalamic Paraventricular and Suprachiasmatic Nuclei of Male and Female Rats
Variations in Phase and Amplitude of Rhythmic Clock Gene Expression across Prefrontal Cortex, Hippocampus, Amygdala, and Hypothalamic Paraventricular and Suprachiasmatic Nuclei of Male and Female Rats
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DOI：
10.1177/0748730415598608
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发表时间：
2015-10-01
影响因子：
3.5
通讯作者：
Spencer, Robert L.
中科院分区：
文献类型：
--
作者：
Chun, Lauren E.;Woodruff, Elizabeth R.;Spencer, Robert L.
分子生物钟是一个由正向(BMal1，Clock/Npas2)和负向(Per1，2，3，Cry1，2)调控组分组成的自我调节转录/翻译循环。虽然在人体主要的昼夜节律起搏器--下丘脑视交叉上核(SCN)中，分子时钟已经被很好地描述了，但只有少数研究同时检测了SCN外脑组织中的正负时钟成分。此外，还没有对大脑中男性和女性时钟基因的表达进行直接比较。这种比较是合理的，因为昼夜节律功能和与时钟基因表达中断相关的紊乱存在性别差异。本研究在12：12小时的光：暗周期中，每隔4小时对雄性和雌性大鼠的SCN、前额叶皮质(PFC)、无颗粒头端岛、下丘脑室旁核(PVN)、杏仁核和海马区的基础时钟基因(PER1、PER2、BMal1)的表达进行了检测。在SCN、PFC、脑岛、PVN、海马亚区和杏仁核有明显的PER1、PER2和BMal1的节律，周期为24小时，这表明在SCN外的脑区有一个振荡的分子时钟的重要性。在大脑区域有3个不同的时钟基因表达谱，表明大脑时钟之间的多样性。尽管一般来说，雄性和雌性大鼠之间的CLOCK基因表达谱相似，但在CLOCK基因表达的稳健性方面存在性别差异(例如，雌性大鼠在PFC内侧的节律较少，在海马区的节律更强健，而在杏仁内侧核的中点较大)。此外，与非发情周期的雌性相比，具有规则发情周期的雌性在PFC中时钟基因表达的聚集节律减弱。这表明性腺激素可能调节分子时钟的表达。
The molecular circadian clock is a self-regulating transcription/translation cycle of positive (Bmal1, Clock/Npas2) and negative (Per1,2,3, Cry1,2) regulatory components. While the molecular clock has been well characterized in the body's master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), only a few studies have examined both the positive and negative clock components in extra-SCN brain tissue. Furthermore, there has yet to be a direct comparison of male and female clock gene expression in the brain. This comparison is warranted, as there are sex differences in circadian functioning and disorders associated with disrupted clock gene expression. This study examined basal clock gene expression (Per1, Per2, Bmal1 mRNA) in the SCN, prefrontal cortex (PFC), rostral agranular insula, hypothalamic paraventricular nucleus (PVN), amygdala, and hippocampus of male and female rats at 4-h intervals throughout a 12:12 h light:dark cycle. There was a significant rhythm of Per1, Per2, and Bmal1 in the SCN, PFC, insula, PVN, subregions of the hippocampus, and amygdala with a 24-h period, suggesting the importance of an oscillating molecular clock in extra-SCN brain regions. There were 3 distinct clock gene expression profiles across the brain regions, indicative of diversity among brain clocks. Although, generally, the clock gene expression profiles were similar between male and female rats, there were some sex differences in the robustness of clock gene expression (e.g., females had fewer robust rhythms in the medial PFC, more robust rhythms in the hippocampus, and a greater mesor in the medial amygdala). Furthermore, females with a regular estrous cycle had attenuated aggregate rhythms in clock gene expression in the PFC compared with noncycling females. This suggests that gonadal hormones may modulate the expression of the molecular clock.