Project Summary

Stephen R. Salton, M.D., Ph.D., (Independent Investigator 2006) of Mount Sinai School of Medicine, points out that growth factors in general, and brain-derived neurotrophic factor (BDNF) in particular, play critical roles in regulating nervous system development and function. Furthermore, many studies suggest that BDNF signaling through its receptor TrkB is involved in the pathophysiology of mood disorders, and is required for the efficacy of antidepressant therapy. His prior work indicates that a BDNF-regulated gene, vgf (non-acronymic), which encodes a secreted neuronal protein and peptide precursor, might be an important mediator of these anti-depressant actions. Hippocampal VGF expression is induced by electroconvulsive therapy and by exercise, both of which produce anti-depressant responses. In addition, a specific C-terminal VGF-derived peptide has been found to have anti-depressant actions. These published and preliminary studies suggest that the gene encoding VGF could be an important mediator of BDNF’s anti-depressant actions. We propose to utilize available VGF mutant mouse models we currently are studying in our lab, and to generate new, powerful conditional models, to assess the anti-depressant function(s) of VGF and VGF-derived peptides. These experiments will test the hypotheses that the secreted protein VGF, a BDNF-inducible neuropeptide precursor, regulates mood and is required for antidepressant therapy. Further study of VGF mutant mice has the potential to elucidate additional downstream targets of BDNF and antidepressant agents, and increase our understanding of the pathophysiology of mood disorders.

Program Area: MOOD DISORDERS

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