Altered expression pattern of clock genes in a rat model of depression

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  • Sofie Christiansen
  • ,
  • Elena Bouzinova
  • Jan Fahrenkrug, Department of clinical medicine, Bispebjerg Hospital, Denmark
  • Ove Wiborg

Abnormalities in circadian rhythms may be causal factors in development of major depressive disorder. The biology underlying a causal relationship between circadian rhythm disturbances and depression is slowly being unraveled. Although there is no direct evidence of dysregulation of clock gene expression in depressive patients many studies have reported single-nucleotide polymorphisms in clock genes in these patients.


In the present study we investigated whether a depression-like state in rats associates with alternations of the diurnal expression of clock genes. The validated chronic mild stress (CMS) animal model of depression was used to investigate rhythmic expression of three clock genes; Per1, Per2 and Bmal1. Brain and liver tissue was collected from 96 animals after 3.5 weeks of CMS (48 control and 48 depression-like rats) at 4 h sampling interval within 24 h. We quantified expression of clock genes on brain sections in the prefrontal cortex, nucleus accumbens, pineal gland, suprachiasmatic nucleus, substantia nigra, amygdala, ventral tegmental area, subfields of the hippocampus, and the lateral habenula using in situ hybridization histochemistry. Expression of clock genes in the liver was monitored by real-time quantitative PCR.


We found that the effect of CMS on clock gene expression was selective and region specific. Per1 exhibits a robust diurnal rhythm in most regions of interest, whereas Bmal1 and in particular Per2 were susceptible to CMS.


The present results suggest that altered expression of investigated clock genes are likely to associate with the induction of a depression-like state in the CMS model
Original languageEnglish
JournalInternational Journal of Neuropsychopharmacology
Pages (from-to)1-13
Number of pages13
Publication statusPublished - Nov 2016

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