Gene expression patterns in a rodent model for depression.
Disturbances in sleep are encountered in the majority of patients with depression. To elucidate the possible molecular mechanisms behind this relationship we examined gene expression changes in a rodent model for depression and disturbed sleep. Animals were treated with daily injections of clomipramine in their early infancy, after which gene expression in basal forebrain was examined using Affymetrix Rat 230.2 chips. We tested the levels of both single transcripts and involved pathways, and searched for common nominators (i.e. transcription factors) that could explain these changes. We identified 72 differentially expressed gene transcripts, many of which are involved in epigenetic regulation, such as DNMT2. Analysis of functional pathways revealed statistically significant changes of the biological process of synaptic transmission, the cellular compartment of the synapse and the molecular function of GABA signalling, showing that transcripts with altered expression are functionally related. Finally, promoter analysis of the differentially expressed genes showed a clear enrichment of binding sites for the transcription factor CREB1, a molecule also involved in epigenetic regulation (cAMP response element-binding protein induces histone modifications). These results indicate that CREB1 may constitute one of the major links between disturbed sleep and mood. The results also highlight the molecular mechanisms in the murine clomipramine model, previously shown to be a valid model for depression.
Lagus
Markus
M
Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Biomedicum, Helsinki, Finland.
Gass
Natalia
N
Saharinen
Juha
J
Saarela
Janna
J
Porkka-Heiskanen
Tarja
T
Paunio
Tiina
T
D000818:Animals; D002997:Clomipramine; D003866:Depressive Disorder / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D016548:Prosencephalon / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D012893:Sleep Wake Disorders / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism
D002997:Clomipramine