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Gene expression patterns in a rodent model for depression
Author(s) -
Lagus Markus,
Gass Natalia,
Saharinen Juha,
Saarela Janna,
PorkkaHeiskanen Tarja,
Paunio Tiina
Publication year - 2010
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07166.x
Subject(s) - rodent , depression (economics) , rodent model , psychology , gene expression , expression (computer science) , neuroscience , computational biology , biology , gene , genetics , computer science , ecology , endocrinology , economics , macroeconomics , programming language
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.