Caputo Rosanna, Poirel Vincent-Joseph, Paiva Isabel, Boutillier Anne-Laurence, Challet Etienne, Meijer Johanna H, Raison Sylvie
Institute of Cellular and Integrative Neurosciences, CNRS and University of Strasbourg, 8 Allée du Général Rouvillois, Strasbourg 67000, France; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden 2333 ZC, the Netherlands.
Institute of Cellular and Integrative Neurosciences, CNRS and University of Strasbourg, 8 Allée du Général Rouvillois, Strasbourg 67000, France.
Neurosci Lett. 2023 Mar 16;799:137091. doi: 10.1016/j.neulet.2023.137091. Epub 2023 Jan 20.
The noradrenergic Locus Cœruleus is one of the major arousal structures involved in inducing wakefulness. While brain noradrenaline (NA) amounts display 24-h variations, the origin of NA rhythm is currently unknown. In this study, we tested the hypothesis that NA rhythm could result from its rhythmic synthesis. Therefore, we investigated the 24-h expression profile of NA rate-limiting enzyme, tyrosine hydroxylase (th), in the Locus Cœruleus (LC) of the nocturnal rat and the diurnal rodent Arvicanthis, under 12 h:12 h light/dark (LD) and constant darkness (DD) conditions. In both species, th mRNA levels vary significantly over 24-h. In nocturnal rats, th mRNA profiles show a unimodal rhythm, with peak values in late day in LD, and in the middle of the subjective day in DD. In contrast, th mRNA rhythm in Arvicanthis is characterized by a bimodal profile, with higher levels at the beginning of the day and of the night in LD, and in the middle of the subjective day and night in DD. The rhythmic pattern of th expression may be dependent on a LC clock machinery. Therefore, we investigated the expression of three clock genes, namely bmal1, per1, and per2, and found that their mRNAs display significant variations between day and nighttime points in both species, but in opposite directions. These data show that NA rhythm may be related to circadian expression of th gene in both species, but differs between nocturnal and diurnal rodents. Furthermore, the phase opposition of clock gene expression in the rat compared to Arvicanthis suggests that the clock machinery might be one of the mechanisms involved in th rhythmic expression.
去甲肾上腺素能蓝斑核是诱导清醒的主要觉醒结构之一。虽然脑去甲肾上腺素(NA)含量呈现24小时变化,但NA节律的起源目前尚不清楚。在本研究中,我们测试了NA节律可能源于其节律性合成的假设。因此,我们研究了夜行性大鼠和昼行性啮齿动物非洲沼鼠蓝斑核(LC)中NA限速酶酪氨酸羟化酶(th)的24小时表达谱,实验条件为12小时光照/12小时黑暗(LD)和持续黑暗(DD)。在这两个物种中,th mRNA水平在24小时内均有显著变化。在夜行性大鼠中,th mRNA谱显示出单峰节律,在LD条件下,峰值出现在白天晚些时候,在DD条件下,峰值出现在主观白天的中间。相比之下,非洲沼鼠的th mRNA节律具有双峰特征,在LD条件下,白天开始和夜晚开始时水平较高,在DD条件下,主观白天和夜晚的中间水平较高。th表达的节律模式可能依赖于蓝斑核的生物钟机制。因此,我们研究了三个生物钟基因bmal1、per1和per2的表达,发现它们的mRNA在两个物种的白天和夜间点之间均有显著变化,但方向相反。这些数据表明,NA节律可能与两个物种中th基因的昼夜表达有关,但在夜行性和昼行性啮齿动物之间存在差异。此外,与非洲沼鼠相比,大鼠生物钟基因表达的相位相反,这表明生物钟机制可能是th节律表达所涉及的机制之一。