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VGF function in depression and antidepressant efficacy.

C Jiang1,2, W-J Lin1, M Sadahiro1,2

  • 1Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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VGF protein levels in the brain are linked to depression. Manipulating VGF in specific brain regions affects depression-like behaviors and antidepressant responses, highlighting its role in mood regulation.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Psychiatry

Background:

  • Brain-derived neurotrophic factor (BDNF) significantly influences depression and antidepressant actions.
  • VGF, a protein regulated by BDNF/TrkB signaling, shows altered expression in depressed individuals and stress models.

Purpose of the Study:

  • To investigate the role of VGF in depression-like behaviors and antidepressant responses.
  • To explore the impact of VGF manipulation in specific brain regions on mood regulation.

Main Methods:

  • Vgf gene ablation and overexpression using adeno-associated virus (AAV)-Cre in floxed VGF mice.
  • Assessment of depression-like behaviors in various mouse models, including chronic social defeat stress (CSDS) and forced swim test.
  • Analysis of VGF peptide effects and involvement of AMPA receptor and mTOR signaling pathways.

Main Results:

  • Vgf ablation in the dorsal hippocampus (dHc) induced pro-depressant behaviors, while NAc ablation had antidepressant effects.
  • VGF overexpression yielded opposite outcomes in dHc and NAc.
  • Reduced VGF levels increased susceptibility to CSDS and impaired ketamine response.
  • VGF-derived peptide TLQP-62 demonstrated rapid antidepressant efficacy in the dHc.

Conclusions:

  • VGF is a critical regulator of depression-like behaviors in the hippocampus and nucleus accumbens.
  • Antidepressant effects, particularly from ketamine, involve rapid VGF translation and are modulated by BDNF signaling.