CREB-regulated diurnal activity patterns are not indicative for depression-like symptoms in mice and men.
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.
Chourbaji
Sabine
S
Central Institute of Mental Health Mannheim (ZI), University of Heidelberg, Germany. chourbaj@zi-mannheim.de
Brandwein
Christiane
C
Gau
Daniel
D
Depner
Martin
M
Saam
Christina
C
Johansson
Carolina
C
Schalling
Martin
M
Partonen
Timo
T
Kasper
Siegfried
S
Adolfsson
Rolf
R
Urani
Alexandre
A
Lemberger
Thomas
T
Schütz
Günther
G
Schumann
Gunter
G
Gass
Peter
P
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
C115163:CREB1 protein, human; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein