RGD Reference Report - VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. - Rat Genome Database

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VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants.

Authors: Warner-Schmidt, JL  Duman, RS 
Citation: Warner-Schmidt JL and Duman RS, Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4647-52. Epub 2007 Mar 5.
RGD ID: 2292006
Pubmed: PMID:17360578   (View Abstract at PubMed)
PMCID: PMC1838655   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0610282104   (Journal Full-text)

The neural mechanisms underlying the cellular and behavioral responses to antidepressants are not yet known. Up-regulation of growth factors and adult neurogenesis suggest a role for one or more of these factors in the action of antidepressants. One candidate of interest is vascular endothelial growth factor (VEGF), which was initially characterized for its role in angiogenesis, but also exerts direct mitogenic effects on neural progenitors in vitro. Results of this study demonstrate that VEGF is induced by multiple classes of antidepressants at time points consistent with the induction of cell proliferation and therapeutic action of these treatments. We find that VEGF signaling through the Flk-1 receptor is required for antidepressant-induced cell proliferation. We also show that VEGF-Flk-1 signaling is required and sufficient for behavioral responses in two chronic and two subchronic antidepressant models. Taken together, these studies identify VEGF and VEGF-Flk-1 signaling as mediators of antidepressant actions and potential targets for therapeutic intervention.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KdrRatpositive regulation of endothelial cell proliferation  IMP in the hippocampal subgranular zoneRGD 
KdrRatresponse to xenobiotic stimulus  IMP antidepressants fluoxetine and desipramineRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KdrRatabnormal depression-related behavior  IDA  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Kdr  (kinase insert domain receptor)


Additional Information