Dysregulation of circadian clock gene expression patterns in a treatment-resistant animal model of depression

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Neurochemistry Pub Date : 2024-07-05 DOI:10.1111/jnc.16172
Kristoffer Højgaard, Erik Kaadt, Birgitte Hviid Mumm, Vitor Silva Pereira, Betina Elfving
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Abstract

Circadian rhythm (CR) disturbances are among the most commonly observed symptoms during major depressive disorder, mostly in the form of disrupted sleeping patterns. However, several other measurable parameters, such as plasma hormone rhythms and differential expression of circadian clock genes (ccgs), are also present, often referred to as circadian phase markers. In the recent years, CR disturbances have been recognized as an essential aspect of depression; however, most of the known animal models of depression have yet to be evaluated for their eligibility to model CR disturbances. In this study, we investigate the potential of adrenocorticotropic hormone (ACTH)-treated animals as a disease model for research in CR disturbances in treatment-resistant depression. For this purpose, we evaluate the changes in several circadian phase markers, including plasma concentrations of corticosterone, ACTH, and melatonin, as well as gene expression patterns of 13 selected ccgs at 3 different time points, in both peripheral and central tissues. We observed no impact on plasma corticosterone and melatonin concentrations in the ACTH rats compared to vehicle. However, the expression pattern of several ccgs was affected in the ACTH rats compared to vehicle. In the hippocampus, 10 ccgs were affected by ACTH treatment, whereas in the adrenal glands, 5 ccgs were affected and in the prefrontal cortex, hypothalamus and liver 4 ccgs were regulated. In the blood, only 1 gene was affected. Individual tissues showed changes in different ccgs, but the expression of Bmal1, Per1, and Per2 were most generally affected. Collectively, the results presented here indicate that the ACTH animal model displays dysregulation of a number of phase markers suggesting the model may be appropriate for future studies into CR disturbances.

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抗药性抑郁症动物模型中昼夜节律钟基因表达模式的失调。
昼夜节律(CR)紊乱是重度抑郁症患者最常出现的症状之一,主要表现为睡眠模式紊乱。然而,其他一些可测量的参数,如血浆激素节律和昼夜节律时钟基因(ccgs)的差异表达,也会出现昼夜节律紊乱,通常被称为昼夜节律相位标记。近年来,昼夜节律紊乱已被认为是抑郁症的一个重要方面;然而,大多数已知的抑郁症动物模型尚未被评估是否有资格作为昼夜节律紊乱的模型。在本研究中,我们调查了促肾上腺皮质激素(ACTH)处理的动物作为研究耐药抑郁症 CR 干扰的疾病模型的潜力。为此,我们评估了几种昼夜节律相位标志物的变化,包括皮质酮、促肾上腺皮质激素和褪黑激素的血浆浓度,以及在 3 个不同时间点,外周和中枢组织中 13 种选定 ccgs 的基因表达模式。与药物相比,我们观察到 ACTH 大鼠的血浆皮质酮和褪黑激素浓度没有受到影响。然而,与药物相比,ACTH 大鼠体内几种 ccgs 的表达模式受到了影响。在海马中,有 10 个 ccgs 受到 ACTH 处理的影响,而在肾上腺中,有 5 个 ccgs 受到影响,在前额叶皮质、下丘脑和肝脏中,有 4 个 ccgs 受到调节。在血液中,只有 1 个基因受到影响。个别组织的不同 ccgs 发生了变化,但 Bmal1、Per1 和 Per2 的表达受到的影响最为普遍。总之,本文介绍的结果表明,促肾上腺皮质激素动物模型显示出许多相位标志物的失调,这表明该模型可能适合于未来对 CR 干扰的研究。
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来源期刊
Journal of Neurochemistry
Journal of Neurochemistry 医学-神经科学
CiteScore
9.30
自引率
2.10%
发文量
181
审稿时长
2.2 months
期刊介绍: Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
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