Table 1.
Potential mTORC1-related biomarkers in animal model of MDD after pharmacological treatment. Summarized are mTORC1-related biomarkers, which are close relative to mTORC1 (mTORC1-proximal), farther downstream to mTORC1 (mTORC1-distal), and upstream to mTORC1. Presented data are based on pre-clinical studies in animals subjected to chronic stress paradigms in which the pharmacological treatment deemed successful, unless stated otherwise.
| References | Biomarker (time after dosing) | |||||
|---|---|---|---|---|---|---|
| mTORC1-proximal | mTORC1-distal | Upstream | AD | Rapid-acting | Drug class/target | |
| Kato and colleagues 13 | mTOR (ph, 1 h) | PSD95 (pr, 24 h) | Ketamine | Yes | NMDA receptor antagonist | |
| p70S6K (ph, 1 h) | GluR1 (pr, 24 h) | |||||
| 4EBP1 (ph, 1 h) | ||||||
| Pazini and colleagues 42 | mTOR (ph, 1 h) | PSD95 (pr, 30 min) | Ketamine | Yes | NMDA receptor antagonist | |
| p70S6K (ph, 1 h) | BDNF (pr) | |||||
| Pazini and colleagues 43 | PSD95 (pr, 1 h) | Ketamine | Yes | NMDA receptor antagonist | ||
| BDNF (pr, 1 h) | ||||||
| Fraga and colleagues 44 | p70S6K (ph, 1 h) | Ketamine | Yes | NMDA receptor antagonist | ||
| Li and colleagues 14 | mTOR (ph, 30 min) | PSD95 (pr, 2 h) | Akt (ph, 1 h) | Ketamine | Yes | NMDA receptor antagonist |
| p70S6K (ph, 30 min) | GluR1 (pr, 2 h) | ERK (ph, 1 h) | ||||
| 4EBP1 (ph, 30 min) | ||||||
| Li and colleagues 35 | PSD95 (pr, 2 days) | Ketamine | Yes | NMDA receptor antagonist | ||
| GluR1 (pr, 2 days) | ||||||
| Liu and colleagues 15 | mTOR (ph, 1 h) | Akt (ph, 1 h) | Ketamine | Yes | NMDA receptor antagonist | |
| p70S6K (ph, 1 h) | ERK (ph, 1 h) | |||||
| GSK-3β (ph, 1 h) | ||||||
| Fukumoto and colleagues 12 | mTOR (ph, 30 min) | Ketamine | Yes | NMDA receptor antagonist | ||
| Tang and colleagues 39 | p70S6K (ph, 2 days) | PSD95 (pr, 2 days) | Akt (ph, 2 days) | Ketamine | Yes | NMDA receptor antagonist |
| 4EBP1 (ph, 2 days) | GluR1 (pr, 2 days) | ERK (ph, 2 days) | ||||
| Liu and colleagues 45 | PSD95 (pr, 2 days) | Ketamine | Yes | NMDA receptor antagonist | ||
| BDNF (pr, 2 days) | ||||||
| Bcl2/Bax (pr, 2 days) | ||||||
| Zhou and colleagues 46 * | mTOR (ph, 30 min) | BDNF (pr, 30 min) | Ketamine | Yes | NMDA receptor antagonist | |
| Yang and colleagues 47 | mTOR (ph, 30 min) | BDNF (pr, 30 min) | Ketamine | Yes | NMDA receptor antagonist | |
| Beurel and colleagues 48 | GSK-3β (ph, 30 min) | Ketamine | Yes | NMDA receptor antagonist | ||
| Autry and colleagues 49 | eEF2K (ph, 30 min) | BDNF (pr, 30 min) | Ketamine | Yes | NMDA receptor antagonist | |
| Silva Pereira and colleagues 50 | BDNF (mRNA, 2 h) | Ketamine | Yes | NMDA receptor antagonist | ||
| Ju and colleagues 51 | BDNF (meth DNA, 23 days) | Ketamine | No | NMDA receptor antagonist | ||
| Pazini and colleagues 42 , Pazini and colleagues 43 | mTOR (ph, 1 h) | PSD95 (pr, 1 h) | Creatine | Yes | Ergogenic guanidine-like compound | |
| p70S6K (ph, 1 h) | BDNF (pr, 1 h) | |||||
| Kato and colleagues 13 | mTOR (ph, 1 h) | PSD95 (pr, 24 h) | NV-5138 | Yes | Leucine analog | |
| p70S6K (ph, 1 h) | GluR1 (pr, 24 h) | |||||
| 4EBP1 (ph, 1 h) | ||||||
| Li and colleagues 14 | mTOR (ph, 1 h) | PSD95 (pr, 6 h) | Akt (ph, 1 h) | Ro 25-6981 | Yes | NMDA receptor NR2B-subunit antagonist |
| p70S6K (ph, 1 h) | GluR1 (pr, 6 h) | ERK (ph, 1 h) | ||||
| 4EBP1 (ph, 1 h) | ||||||
| Fukumoto and colleagues 12 | mTOR (ph, 30 min) | BDNF** (pr, 1 h) | ERK** (ph, 1 h) | (2R,6R)-HNK | Yes | Ketamine metabolite |
| Voleti and colleagues 52 | mTOR (ph, 1 h) | Akt (ph, 1 h) | Scopolamine | Yes | Muscarinic receptor antagonists | |
| p70S6K (ph, 1 h) | ||||||
| Voleti and colleagues 52 | mTOR (ph, 1 h) | Akt (ph, 1 h) | Telenzepine | Yes | Muscarinic receptor antagonists | |
| p70S6K (ph, 2 h) | ERK (ph, 1 h) | |||||
| Fogaça and colleagues 11 | p70S6K (ph, 24 h) | PSD95 (pr, 24 h) | ERK** (ph, 1 h) | d-methadone | Yes | Opioid |
| GluR1 (pr, 24 h) | ||||||
| BDNF** (pr, 1 h) | ||||||
| Autry and colleagues 49 | eEF2K (ph, 30 min) | PSD95 (pr, 30 min) | MK-801/dizocilpine | Yes | NMDA receptor antagonist | |
| BDNF (pr, 30 min) | ||||||
| Suzuki and colleagues 53 | mTOR ** (ph, 1 h) | BDNF** (pr, 1 h) | Akt** (ph, 1 h) | TAK-137 | Yes | AMPA receptor potentiator |
| p70S6K ** (ph, 1 h) | ERK** (ph, 1 h) | |||||
Pr, protein; ph, phosphorylated protein; meth DNA, gene methylation; min, minute; h, hour; d, day; w, week. For all other abbreviations, see list of abbreviations.
*
Animals not exposed to stress.
**
Biomarker measured in cortical cell culture.