Antidepressant actions of the exercise-regulated gene VGF

Joshua G. Hunsberger, Samuel S. Newton, Alicia H. Bennett, Catharine H. Duman, David S. Russell, Stephen R. Salton, Ronald S. Duman

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

Exercise has many health benefits, including antidepressant actions in depressed human subjects, but the mechanisms underlying these effects have not been elucidated. We used a custom microarray to identify a previously undescribed profile of exercise-regulated genes in the mouse hippocampus, a brain region implicated in mood and antidepressant response. Pathway analysis of the regulated genes shows that exercise upregulates a neurotrophic factor signaling cascade that has been implicated in the actions of antidepressants. One of the most highly regulated target genes of exercise and of the growth factor pathway is the gene encoding the VGF nerve growth factor, a peptide precursor previously shown to influence synaptic plasticity and metabolism. We show that administration of a synthetic VGF-derived peptide produces a robust antidepressant response in mice and, conversely, that mutation of VGF in mice produces the opposite effects. The results suggest a new role for VGF and identify VGF signaling as a potential therapeutic target for antidepressant drug development.

Original languageEnglish (US)
Pages (from-to)1476-1482
Number of pages7
JournalNature Medicine
Volume13
Issue number12
DOIs
StatePublished - Dec 1 2007

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Antidepressive Agents
Genes
Peptides
Neuronal Plasticity
Gene encoding
Nerve Growth Factors
Nerve Growth Factor
Insurance Benefits
Microarrays
Metabolism
Plasticity
Hippocampus
Brain
Intercellular Signaling Peptides and Proteins
Up-Regulation
Health
Mutation
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hunsberger, J. G., Newton, S. S., Bennett, A. H., Duman, C. H., Russell, D. S., Salton, S. R., & Duman, R. S. (2007). Antidepressant actions of the exercise-regulated gene VGF. Nature Medicine, 13(12), 1476-1482. https://doi.org/10.1038/nm1669

Antidepressant actions of the exercise-regulated gene VGF. / Hunsberger, Joshua G.; Newton, Samuel S.; Bennett, Alicia H.; Duman, Catharine H.; Russell, David S.; Salton, Stephen R.; Duman, Ronald S.

In: Nature Medicine, Vol. 13, No. 12, 01.12.2007, p. 1476-1482.

Research output: Contribution to journalArticle

Hunsberger, JG, Newton, SS, Bennett, AH, Duman, CH, Russell, DS, Salton, SR & Duman, RS 2007, 'Antidepressant actions of the exercise-regulated gene VGF', Nature Medicine, vol. 13, no. 12, pp. 1476-1482. https://doi.org/10.1038/nm1669
Hunsberger JG, Newton SS, Bennett AH, Duman CH, Russell DS, Salton SR et al. Antidepressant actions of the exercise-regulated gene VGF. Nature Medicine. 2007 Dec 1;13(12):1476-1482. https://doi.org/10.1038/nm1669
Hunsberger, Joshua G. ; Newton, Samuel S. ; Bennett, Alicia H. ; Duman, Catharine H. ; Russell, David S. ; Salton, Stephen R. ; Duman, Ronald S. / Antidepressant actions of the exercise-regulated gene VGF. In: Nature Medicine. 2007 ; Vol. 13, No. 12. pp. 1476-1482.
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