Journal of Clinical Investigation
April 16, 2019
T. Kato, Santosh Pothula, Rong-Jian Liu et al.
88 citations
Preclinical studies demonstrate that rapid acting antidepressants, including ketamine require stimulation of mTORC1 signaling. This pathway is regulated by neuronal activity, endocrine and metabolic signals, notably the amino acid leucine, which activates mTORC1 signaling via binding to the upstream regulator sestrin. Here, we examined the antidepressant actions of NV-5138, a novel highly...
American Journal of Psychiatry
January 4, 2019
Satoshi Deyama, Eunyoung Bang, Eric S. Wohleb et al.
100 citations
OBJECTIVE: -methyl-d-aspartate receptor antagonist ketamine produces rapid and sustained antidepressant actions even in patients with treatment-resistant depression. Vascular endothelial growth factor (VEGF) has been implicated in the effects of conventional monoamine-based antidepressants, but the role of VEGF in the rapid antidepressant actions of ketamine remains unclear. The authors...
Proceedings of the National Academy of Sciences
December 17, 2018
Kenichi Fukumoto, Manoela V. Fogaça, Rong-Jian Liu et al.
191 citations
Significance A metabolite of ketamine, (2 R ,6 R )-hydroxynorketamine [(2 R ,6 R )-HNK], produces rapid and sustained antidepressant effects in animal models but without the side effects of ketamine. Notably, (2 R ,6 R )-HNK does not block the NMDA receptor, the primary target of ketamine. Here, we demonstrate that the antidepressant effects of (2 R ,6 R )-HNK require activity dependent release...
Proceedings for Annual Meeting of The Japanese Pharmacological Society
2018
Satoshi Deyama, Eunyoung Baing, T. Kato et al.
Previous studies have shown that activity-dependent release of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) is required for the antidepressant actions of ketamine. Recently, we have found that neuronal vascular endothelial growth factor (VEGF),signaling in the mPFC also plays a crucial role in the antidepressant actions of this rapid acting agent. However, it...