Deficiency of the circadian clock gene Rev-erbα induces mood disorder-like behaviours and dysregulation of the serotonergic system in mice

Otsuka, Tsuyoshi; Le, Hue Thi; Thein, Zaw Lin; Ihara, Hayato; Sato, Fuyuki; Nakao, Tomomi; Kohsaka, Akira

doi:10.1016/j.physbeh.2022.113960

Cited by 10 publications

(4 citation statements)

References 59 publications

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“…This is consistent with alterations in clock genes in mice under 27 h light‐dark cycle conditions 28 and with the shift model mice 26 . Importantly, these clock genes have been shown to be associated with mood 54–57 . Notably, there was significant overexpression of Bmal1 mRNA in the PFC and hippocampus at night and the changes in protein expression were consistent with the changes in mRNA.…”

Section: Discussionsupporting

confidence: 81%

“…26 Importantly, these clock genes have been shown to be associated with mood. [54][55][56][57] Notably, there was significant overexpression of Bmal1 mRNA in the PFC and hippocampus at night and the changes in protein expression were consistent with the changes in mRNA. Previous studies in mice and nonhuman primates have shown that Bmal1 knockdown leads to anxiety and depression-like behavior.…”

Section: Discussionsupporting

confidence: 54%

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Circadian misalignment impairs oligodendrocyte myelination via Bmal1 overexpression leading to anxiety and depression‐like behaviors

Zuo,

Hou,

Wang

et al. 2024

Journal of Pineal Research

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Circadian misalignment (CM) caused by shift work can increase the risk of mood impairment. However, the pathological mechanisms underlying these deficits remain unclear. In the present study, we used long‐term variable photoperiod (L‐VP) in wild‐type mice to better simulate real‐life shift patterns and study its effects on the prefrontal cortex (PFC) and hippocampus, which are closely related to mood function. The results showed that exposure to L‐VP altered the activity/rest rhythms of mice, by eliciting phase delay and decreased amplitude of the rhythms. Mice with CM developed anxiety and depression‐like manifestations and the number of mature oligodendrocytes (OL) was reduced in the medial prefrontal cortex and hippocampal CA1 regions. Mood impairment and OL reduction worsened with increased exposure time to L‐VP, while normal photoperiod restoration had no effect. Mechanistically, we identified upregulation of Bmal1 in the PFC and hippocampal regions of CM mice at night, when genes related to mature OL and myelination should be highly expressed. CM mice exhibited significant inhibition of the protein kinase B (AKT)/mTOR signaling pathway, which is directly associated to OL differentiation and maturation. Furthermore, we demonstrated in the OL precursor cell line Oli‐Neu that overexpression of Bmal1 inhibits AKT/mTOR pathway and reduces the expression of genes OL differentiation. In conclusion, BMAL1 might play a critical role in CM, providing strong research evidence for BMAL1 as a potential target for CM therapy.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 54%

Circadian misalignment impairs oligodendrocyte myelination via Bmal1 overexpression leading to anxiety and depression‐like behaviors

Zuo,

Hou,

Wang

et al. 2024

Journal of Pineal Research

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“…Disruptions in sleep disorders patterns, diurna activity, hormone secretion, and other physiological processes regulated by the circadian clock represent core features of depressive disorders [ 11 , 20 – 21 ]. While some CRGs located in the suprachiasmatic nucleus region of the hypothalamus, such as 5-hydroxytryptamine (5-HT), Basic helix-loop-helix ARNT-like protein 1 (BMAL1), Peroxidase 1-3 (Per 1-3), Nuclear receptor subfamily 1 group D member 1 (NR1D1), and D site-binding protein (DBP), have been observed in patients with MDD, the intricate functions of these CRGs pose formidable obstacles to their utilization as potential targets for the prevention, diagnosis, and treatment of the disorder [ 22 , 23 ]. Fortuitously, the advent of bioinformatics and machine learning techniques has rendered the elucidation of disease pathogenic mechanisms and the identification of prospective disease biomarkers more feasible endeavors.…”

Section: Discussionmentioning

confidence: 99%

Mining key circadian biomarkers for major depressive disorder by integrating bioinformatics and machine learning

Shi,

Zhu,

Hou

et al. 2024

Aging

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“…[ 20 ] Otsuka et al demonstrated that the Rev-erbα gene can regulate negative emotions and behaviors in mice by acting on the 5-hydroxytryptaminergic system. [ 21 ] The hypothalamic–pituitary–adrenal (HPA) axis is a significant part of the neuroendocrine system, which is involved in controlling the response to stress. When the HPA axis is activated, the paraventricular nucleus of the hypothalamus releases corticotropin-releasing hormone, thereby signaling the anterior pituitary gland to secrete adrenocorticotropic hormone into the blood stream, which in turn acts on the adrenal cortex to stimulate the secretion of cortisol (CORT).…”

Section: Biological Clock Genes Regulate the Physiological And Pathol...mentioning

confidence: 99%

Antidepressant mechanism of traditional Chinese medicine: Involving regulation of circadian clock genes

Lv,

Huang,

et al. 2024

Medicine

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Numerous studies have demonstrated an intimate relationship between circadian rhythm disorders and the development and prevention of depression. The biological clock genes, which constitute the molecular basis of endogenous circadian rhythms, hold promising prospects for depression treatment. Based on an extensive review of recent domestic and international research, this article presents a comprehensive analysis of how traditional Chinese medicine (TCM) intervenes in depression by regulating circadian rhythms. The findings indicate that TCM exerts its antidepressant effects by targeting specific biological clock genes such as Bmal1, clock, Arntl, Per1, Per2, Per3, Nr1d1, Cry2, and Dbp, as well as regulating circadian rhythms of hormone secretion. However, most current research is still confined to basic experimental studies, lacking clinical double-blind control trials to further validate these viewpoints. Furthermore, there is insufficient research on the signal transduction pathway between biological clock genes and pathological changes in depression. Additionally, further clarification is needed regarding the specific targets of TCM on the biological clock genes.

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Deficiency of the circadian clock gene Rev-erbα induces mood disorder-like behaviours and dysregulation of the serotonergic system in mice

Cited by 10 publications

References 59 publications

Circadian misalignment impairs oligodendrocyte myelination via Bmal1 overexpression leading to anxiety and depression‐like behaviors

Circadian misalignment impairs oligodendrocyte myelination via Bmal1 overexpression leading to anxiety and depression‐like behaviors

Mining key circadian biomarkers for major depressive disorder by integrating bioinformatics and machine learning

Antidepressant mechanism of traditional Chinese medicine: Involving regulation of circadian clock genes

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