Translational Psychiatry
January 27, 2020
Kai Zhang, Chun Yang, Lijia Chang et al.
120 citations
In mice with depression-like symptoms from chronic social defeat stress, (R)-ketamine produced more potent and longer-lasting antidepressant effects than (S)-ketamine. RNA sequencing of the prefrontal cortex showed that transforming growth factor (TGF)-β signaling may explain these differences. (R)-ketamine, but not (S)-ketamine, reversed reduced expression of Tgfb1 and its receptors in the prefrontal cortex and hippocampus. Blocking TGF-β1 with inhibitors or a neutralizing antibody prevented (R)-ketamine's antidepressant effects. Depleting microglia also blocked these effects. Recombinant TGF-β1 itself produced rapid and lasting antidepressant effects in mice, suggesting a microglial TGF-β1-dependent mechanism and potential for new human antidepressants.
Scientific Reports
June 5, 2017
Ze-Min Xie, Xingming Wang, Ning Xu et al.
69 citations
Rats with neuropathic pain that also developed depression-like behaviors had higher levels of pro-inflammatory cytokines (interleukin-1β and interleukin-6) and an imbalance between pro- and anti-inflammatory cytokines, along with lower levels of brain-derived neurotrophic factor in the prefrontal cortex, compared to rats without depression-like behaviors and sham-operated controls. A single dose of ketamine reversed both the depression-like behaviors and the elevated serum levels of IL-1β and IL-6. These findings suggest that changes in inflammatory cytokines and BDNF may underlie depression caused by neuropathic pain, and that serum cytokines could serve as biomarkers for ketamine's antidepressant effects.
Journal of Anesthesia and Translational Medicine
July 11, 2024
Kenji Hashimoto, Mingming Zhao, Tingting Zhu et al.
32 citations
Ketamine and its enantiomers have a long history in anesthesia and are now gaining attention for rapid-acting antidepressant effects in severe depression. Esketamine, the (S)-enantiomer, received approval in the U.S. and Europe in 2019 as a nasal spray for depression, but concerns about long-term efficacy, addiction, and suicide risk persist. In rodent models, arketamine, the (R)-enantiomer, shows superior and longer-lasting antidepressant effects with fewer side effects than esketamine, though human research on arketamine is limited. The article reviews the historical use of ketamine and its enantiomers in anesthesia and psychiatry and explores future directions.