Role of a VGF/BDNF/TrkB Autoregulatory Feedback Loop in Rapid-Acting Antidepressant Efficacy.
Cheng Jiang, Wei-Jye Lin, Stephen R Salton
Journal of Molecular Neuroscience July 2019 DOI: 10.1007/s12031-018-1124-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Ketamine GLYX-13 TLQP-62 |
| Measures | Forced swim test (FST) |
| Topics | Ketamine |
| Keywords | Antidepressant Local protein synthesis Vgf |
| Key findings | The authors review evidence that rapid-acting antidepressants such as ketamine and GLYX-13 require VGF expression for efficacy, and that the VGF-derived peptide TLQP-62 has antidepressant efficacy in the forced swim test following intracerebroventricular or intra-hippocampal administration, requiring BDNF, mTOR, and AMPA receptor activation. They propose a rapidly induced autoregulatory feedback loop involving VGF, TLQP-62, BDNF/TrkB, mTOR, and AMPA receptors that may be critical for sustained antidepressant efficacy, depression-like behavior, and cognition. |
Abstract
Members of the neurotrophin family and in particular brain-derived neurotrophic factor (BDNF) regulate the response to rapid- and slow-acting chemical antidepressants and voluntary exercise. Recent work suggests that rapid-acting antidepressants that modulate N-methyl-D-aspartate receptor (NMDA-R) signaling (e.g., ketamine and GLYX-13) require expression of VGF (non-acronymic), the BDNF-inducible secreted neuronal protein and peptide precursor, for efficacy. In addition, the VGF-derived C-terminal peptide TLQP-62 (named by its 4 N-terminal amino acids and length) has antidepressant efficacy following icv or intra-hippocampal administration, in the forced swim test (FST). Similar to ketamine, the rapid antidepressant actions of TLQP-62 require BDNF expression, mTOR activation (rapamycin-sensitive), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activation (NBQX-sensitive) and are associated with GluR1 insertion. We review recent findings that identify a rapidly induced autoregulatory feedback loop, which likely plays a critical role in sustained efficacy of rapid-acting antidepressants, depression-like behavior, and cognition, and requires VGF, its C-terminal peptide TLQP-62, BDNF/TrkB signaling, the mTOR pathway, and AMPA receptor activation and insertion.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cited by 7
- Transient Stimulation with Psychoplastogens Is Sufficient to Initiate Neuronal Growth ACS Pharmacology & Translational Science September 11, 2020
- Rapid-acting antidepressants. Advances in pharmacology (San Diego, Calif.) 2019
- Rapid-Acting Antidepressants Current Pharmaceutical Design October 19, 2018
- The endogenous opioid system in the medial prefrontal cortex mediates ketamine's antidepressant-like actions. Translational Psychiatry February 12, 2024
- (2R, 6R)-hydroxynorketamine ameliorates PTSD-like behaviors during the reconsolidation phase of fear memory in rats by modulating the VGF/BDNF/GluA1 signaling pathway in the hippocampus. Behavioural Brain Research January 5, 2025
and 2 more in the library
Cites 7
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
- BDNF Release Is Required for the Behavioral Actions of Ketamine The International Journal of Neuropsychopharmacology October 31, 2014
- BDNF — a key transducer of antidepressant effects Neuropharmacology November 11, 2015
and 2 more in the library