title: CREB-regulated diurnal activity patterns are not indicative for depression-like symptoms in mice and men.
abstract: Activation of the transcription factor CREB by Ser142 phosphorylation is implicated in synchronizing circadian rhythmicity, which is disturbed in many depressive patients. Hence, one could assume that emotional behaviour and neuroendocrinological markers would be altered in CREB(S142A) mice, in which serine 142 is replaced by alanine, preventing phosphorylation at this residue. Moreover, associations of CREB Ser142 and seasonal affective disorder (SAD) might be detectable by the analysis of single-nucleotide polymorphisms (SNPs) in the CREB gene close to the Ser142 residue in SAD patients. However, neither CREB(S142A) mice demonstrate features of depression, nor there is evidence for an association of SAD with the CREB genotypes. Nevertheless, in humans there is an association of a global seasonality score and circadian rhythmicity with the CREB genotypes in healthy control probands, but not SAD patients. This parallels the phenotype of CREB(S142A) mice, presenting alterations of circadian rhythm and light-induced entrainment. Thus it is reasonable to assume that CREB Ser142 represents a molecular switch in mice and men, which is responsible for the (dys)regulation of circadian rhythms.
authors.affiliation: Central Institute of Mental Health Mannheim (ZI), University of Heidelberg, Germany. chourbaj@zi-mannheim.de
authors.forename: Sabine
authors.initials: S
authors.lastname: Chourbaji
authors.forename: Christiane
authors.initials: C
authors.lastname: Brandwein
authors.forename: Daniel
authors.initials: D
authors.lastname: Gau
authors.forename: Martin
authors.initials: M
authors.lastname: Depner
authors.forename: Christina
authors.initials: C
authors.lastname: Saam
authors.forename: Carolina
authors.initials: C
authors.lastname: Johansson
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.forename: Timo
authors.initials: T
authors.lastname: Partonen
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.forename: Rolf
authors.initials: R
authors.lastname: Adolfsson
authors.forename: Alexandre
authors.initials: A
authors.lastname: Urani
authors.forename: Thomas
authors.initials: T
authors.lastname: Lemberger
authors.forename: Günther
authors.initials: G
authors.lastname: Schütz
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
authors.forename: Peter
authors.initials: P
authors.lastname: Gass
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D003863:Depression / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D051379:Mice; D008960:Models, Psychological; D016574:Seasonal Affective Disorder / Q000503:physiopathology
chemical_list: C115163:CREB1 protein, human; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein