title: Altered Expression Pattern of Clock Genes in a Rat Model of Depression.
abstract: 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 is associated 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: period genes 1 and 2 (Per1 and 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 a 4h sampling interval within 24h. 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 polymerase chain reaction (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 is likely associated with the induction of a depression-like state in the CMS model.
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark (Drs Christiansen, Bouzinova, and Wiborg); Department of Clinical Biochemistry, Faculty of Health Sciences, University of Copenhagen, Denmark (Dr Fahrenkrug).
authors.forename: S L
authors.initials: SL
authors.lastname: Christiansen
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark (Drs Christiansen, Bouzinova, and Wiborg); Department of Clinical Biochemistry, Faculty of Health Sciences, University of Copenhagen, Denmark (Dr Fahrenkrug).
authors.forename: E V
authors.initials: EV
authors.lastname: Bouzinova
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark (Drs Christiansen, Bouzinova, and Wiborg); Department of Clinical Biochemistry, Faculty of Health Sciences, University of Copenhagen, Denmark (Dr Fahrenkrug).
authors.forename: J
authors.initials: J
authors.lastname: Fahrenkrug
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark (Drs Christiansen, Bouzinova, and Wiborg); Department of Clinical Biochemistry, Faculty of Health Sciences, University of Copenhagen, Denmark (Dr Fahrenkrug). ove.wiborg@clin.au.dk.
authors.forename: O
authors.initials: O
authors.lastname: Wiborg
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002940:Circadian Rhythm; D003863:Depression / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D005247:Feeding Behavior; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D056930:ARNTL Transcription Factors; C000598703:Arntl protein, rat; D019422:Dietary Sucrose; C539024:Per1 protein, rat; C513311:Per2 protein, rat; D056950:Period Circadian Proteins
keywords: animal model; circadian rhythm; clock gene expression; depression; stress