Neuropharmacology
September 1, 2022
Hao-Ming Hua, Chao Huang, Hanyu Liu et al.
35 citations
Ketamine's rapid antidepressant effects, a major advance in depression treatment, may involve the gut-brain axis. This review examines how ketamine and its metabolites interact with the gut microbiome and microbiota-derived molecules. The proposed mechanisms include modulation of the stress response, promotion of brain-derived neurotrophic factor (BDNF)-mediated neurogenesis, anti-inflammatory effects, and regulation of neurotransmitters. However, the exact mechanisms remain unclear.
Translational Psychiatry
September 3, 2021
Chao Huang, Yuanyuan Wang, Zifeng Wu et al.
29 citations
Ketamine acts as a rapid and long-lasting antidepressant, but its molecular mechanisms are unclear. In mice subjected to chronic social stress, microRNA miR-98-5p was downregulated in the prefrontal cortex and hippocampus. Overexpressing miR-98-5p with an agonist alleviated depression-like behaviors. Ketamine administration upregulated miR-98-5p, and inhibiting it with an antagonist blocked ketamine's antidepressant effect. This suggests a novel molecular mechanism for ketamine's action and that targeting miR-98-5p could be beneficial for depression treatment.
Brain, behavior, and immunity
October 1, 2023
Xinying Zhang, Teng He, Zifeng Wu et al.
In a mouse model of depression induced by lipopolysaccharide, CD38 expression increased in the hippocampus and cortex. Pharmacological inhibition or genetic knockout of CD38 reduced neuroinflammation, microglia activation, synaptic defects, and Sirt1/STAT3 signaling, and improved depression-like behaviors. Optogenetic activation of glutamatergic neurons in the hippocampal CA3 region reduced depression susceptibility and lowered CD38 expression. The antidepressant (R)-ketamine suppressed CD38 expression and reversed synaptic defects. Hippocampal CD38 is closely linked to depressive behaviors in this inflammation model, suggesting it as a potential therapeutic target.