In a mouse model of depression, (R)-ketamine produces longer-lasting antidepressant effects than (S)-ketamine. The study identifies a molecular pathway in microglia—cells in the brain's medial prefrontal cortex—that mediates these effects. (R)-ketamine activates the ERK-NRBP1-CREB-BDNF signaling cascade in microglia, increasing BDNF transcription. Blocking this pathway with specific inhibitors or depleting microglia prevented (R)-ketamine's antidepressant-like effects and its ability to restore reduced dendritic spine density. These findings suggest that microglial signaling is essential for (R)-ketamine's antidepressant actions.
Emerging viruses like monkeypox virus and SARS-CoV-2 can cause depression by triggering neuroinflammation, immune dysfunction, and neurotransmitter imbalances. Standard antidepressants often work poorly for post-viral depression. Ketamine and its enantiomers S-ketamine and R-ketamine show promise as rapid-acting antidepressants, especially for treatment-resistant depression. This review describes the mechanisms linking viral infections to depression and the antidepressant actions of ketamine compounds. Preliminary reports suggest effectiveness, but more studies are needed to establish optimal treatment strategies, long-term safety, and clinical integration for depression associated with emerging viral infections.