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. 2024 Sep;168(9):1826-1841.
doi: 10.1111/jnc.16172. Epub 2024 Jul 5.

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

Kristoffer Højgaard  1 , Erik Kaadt  1 , Birgitte Hviid Mumm  1 , Vitor Silva Pereira  1 , Betina Elfving  1
Affiliations

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

Kristoffer Højgaard et al. J Neurochem. 2024 Sep.

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.

Keywords: ACTH model; circadian clock genes; circadian rhythm disturbances; major depressive disorder; stress.

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References

REFERENCES

    1. Alario, P., Gamallo, A., Beato, M. J., & Trancho, G. (1987). Body weight gain, food intake and adrenal development in chronic noise stressed rats. Physiology & Behavior, 40, 29–32.
    1. Al‐Safadi, S., Branchaud, M., Rutherford, S., & Amir, S. (2015). Glucocorticoids and stress‐induced changes in the expression of PERIOD1 in the rat forebrain. PLoS One, 10, e0130085.
    1. Arias‐de la Torre, J., Vilagut, G., Ronaldson, A., Serrano‐Blanco, A., Martín, V., Peters, M., Valderas, J. M., Dregan, A., & Alonso, J. (2021). Prevalence and variability of current depressive disorder in 27 European countries: A population‐based study. The Lancet. Public Health, 6, e729–e738.
    1. Baggs, J. E., Price, T. S., DiTacchio, L., Panda, S., FitzGerald, G. A., & Hogenesch, J. B. (2009). Network features of the mammalian circadian clock. PLoS Biology, 7, e1000052.
    1. Bartlang, M. S., Savelyev, S. A., Johansson, A. S., Reber, S. O., Helfrich‐Förster, C., & Lundkvist, G. B. (2014). Repeated psychosocial stress at night, but not day, affects the central molecular clock. Chronobiology International, 31, 996–1007.

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