VGF function in depression and antidepressant efficacy

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.