Altered Expression Pattern of Clock Genes in a Rat Model of Depression

Christiansen, S.; Bouzinova, EV; Fahrenkrug, Jan; Wiborg, Ove

doi:10.1093/ijnp/pyw061

Cited by 63 publications

(58 citation statements)

References 67 publications

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“…Some drugs cannot induce antidepressant effects in animal models of depression even though they have antidepressant effects in normal animals [5253]. Patients with depression and animal models of depression sometimes show disturbances in circadian system functionality [678545556]. Chronopharmacological profiles of antidepressant activity in depressive-like animals could be different from those in normal animals.…”

Section: Discussionmentioning

confidence: 99%

Time of Administration of Acute or Chronic Doses of Imipramine Affects its Antidepressant Action in Rats

Kawai¹,

Kodaira²,

Tanaka³

et al. 2018

Journal of Circadian Rhythms

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The pathogenesis and therapeutics of depression are linked to the operation of the circadian system. Here, we studied the chronopharmacological action of a tricyclic antidepressant, imipramine. Male adult Wistar–Hannover rats were administered imipramine acutely or chronically in the morning or in the evening. The antidepressant action of imipramine was analyzed using the forced swim test (FST). A single dose of imipramine (30 mg/kg) in the morning, but not in the evening, reduced immobility and increased climbing in the FST. The plasma concentrations of imipramine and its metabolite, desipramine, were slightly higher in the morning than in the evening, which might explain the dosing time-dependent action of imipramine. Next, we analyzed the effect of chronic imipramine treatment. Rats received imipramine in the morning or in the evening for 2 weeks. The morning treatment resulted in larger effects in the FST than the evening treatment, and was effective at a dose that was ineffective when administered acutely. The levels of brain α-adrenergic receptors tended to decrease after chronic imipramine treatment. Imipramine might interact with noradrenergic neurons, and this interaction might chronically alter receptor expression. This alteration seemed greater in the morning than in the evening, which might explain the dosing time-dependent action of imipramine.

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Section: Discussionmentioning

confidence: 99%

Time of Administration of Acute or Chronic Doses of Imipramine Affects its Antidepressant Action in Rats

Kawai¹,

Kodaira²,

Tanaka³

et al. 2018

Journal of Circadian Rhythms

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“…It has been reported that 2-10% of the genes in the mammalian genome are controlled by clock genes, and these are known as clock-control genes (CCGs) (13)(14)(15). Aberrant expression of clock genes can regulate downstream clock-control genes and cause various diseases, such as cancer, endocrine diseases, cardiovascular illnesses, and depression (3,6,(16)(17)(18). The International Agency for Research on Cancer have identified that the carcinogenesis of aberrant expression of clock genes is equal to that of diesel engine exhaust gas, inorganic lead compounds, and human papilloma virus (19).…”

Section: Introductionmentioning

confidence: 99%

The circadian clock gene PER2 plays an important role in tumor suppression through regulating tumor-associated genes in human oral squamous cell carcinoma

Chen

Yang

et al. 2017

Oncology Reports

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Abstract. Low expression of the clock gene PER2 is closely related to carcinogenesis and the development of cancer; however, the mechanism of the low expression of PER2 that led to cell malignant transformation remains unclear. This study used RNA interference (RNAi) technology to silence PER2 in SCC15 human oral squamous cell carcinoma (OSCC) cells. Then it was found that the ability of cancer cell proliferation, migration, and invasion were markedly increased (P<0.05), and the ability of cancer cell apoptosis and the number of cells in G1/G0 phase were markedly reduced (P<0.05) after PER2 knockdown. PER2 knockdown increased the expression of MDM2, MMP2, and VEGF mRNA (P<0.05), and decreased the expression of p53, Bax, and TIMP-2 mRNA (P<0.05). The in vivo experiments also proved that the tumorigenicity of SCC15 cells was significantly enhanced after PER2 silence (P<0.05). Overall, these results show that PER2 through the regulation of the numerous important downstream tumor-related genes, plays a major role in tumor suppression, and it may be a novel molecular target for cancer treatment.

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“…Thus, we predict that that stress induced pathophysiological firing in the loop consisting of the LHb, DRN and SCN (LHb®DRN®SCN®LHb) may be responsible for changes in daily rhythms associated with mood disorders. Stress and the circadian system exhibit 2way interaction where for example clock proteins CRY 1/2 increase the responsiveness of the HPA-axis (20) while stress-induced increase in glucocorticoids leads to altered clock gene expression in the SCN and regions associated with regulation of mood(21), (22). Stress induces increased firing in the LHb has been shown to activate HPA-axis causing elevated corticosterone release(23).…”

Section: Discussionmentioning

confidence: 99%

Blunted Diurnal Firing in Lateral Habenula Projections to Dorsal Raphe Nucleus and Delayed Photoentrainment in Stress-Susceptible Mice

Liu

Rastogi

Šabanović

et al. 2020

Preprint

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Daily rhythms are disrupted in patients suffering from mood disorders. The lateral habenula (LHb) and dorsal raphe nucleus (DRN) contribute to circadian timekeeping and regulate mood. Thus, pathophysiology in these nuclei may be responsible for aberrations in daily rhythms during mood disorders. Using the chronic social defeat stress (CSDS) paradigm and in-vitro slice electrophysiology we measured the effects of stress on diurnal rhythms in firing of LHb cells projecting to the DRN (cells LHb®DRN ) and DRN cells alone.We also performed optogenetic experiments to investigate if increased firing in cells LHb®DRN during exposure to subthreshold social defeat stress (SSDS), induces stresssusceptibility. Last we investigated whether exposure to CSDS affected the ability of mice to phototentrain to a new LD cycle. The cells LHb®DRN and DRN cells alone of stresssusceptible mice express greater blunted diurnal firing compared to stress-naive (control) and stress-resilient mice. Day-time optogenetic activation of cells LHb®DRN during SSDS induces stress-susceptibility which shows the direct correlation between increased activity in this circuit and putative mood disorders. Finally, we found that stresssusceptible mice are slower, while stress-resilient mice are faster, at photoentraining to a new LD cycle. Our findings suggest that CSDS induces blunted daily rhythms in firing in cells LHb®DRN and slow rate of photoentrainment in susceptible-mice. In contrast, resilientmice may undergo homeostatic adaptations that maintain daily rhythms in firing in cells LHb®DRN and also show rapid photoentrainment to a new LD-cycle.

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Altered Expression Pattern of Clock Genes in a Rat Model of Depression

Cited by 63 publications

References 67 publications

Time of Administration of Acute or Chronic Doses of Imipramine Affects its Antidepressant Action in Rats

Time of Administration of Acute or Chronic Doses of Imipramine Affects its Antidepressant Action in Rats

The circadian clock gene PER2 plays an important role in tumor suppression through regulating tumor-associated genes in human oral squamous cell carcinoma

Blunted Diurnal Firing in Lateral Habenula Projections to Dorsal Raphe Nucleus and Delayed Photoentrainment in Stress-Susceptible Mice

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