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• LPS-induced depression associates with increased CD38 levels in selected brain regions. • Inhibiting CD38 relieves depression-like behaviors via regulating neuroinflammation and synaptic function. • Inhibiting CD38 decreases excessive microglia activation via Sirt1-STAT3-NF-кB signaling pathway. • Neuronal activation in CA3 of hippocampus produces antidepressant effects. • The antidepressant effects of (R)-ketamine are related to decreased CD38 levels. CD38 is involved in immune responses, cell proliferation, and has been identified in the brain, where it is implicated in inflammation processes and psychiatric disorders. We hypothesized that dysfunctional CD38 activity in the brain may contribute to the pathogenesis of depression. To investigate the underlying mechanisms, we used a lipopolysaccharide (LPS)-induced depression-like model and conducted behavioral tests, molecular and morphological methods, along with optogenetic techniques. We microinjected adeno-associated virus into the hippocampal CA3 region with stereotaxic instrumentation. Our results showed a marked increase in CD38 expression in both the hippocampus and cortex of LPS-treated mice. Additionally, pharmacological inhibition and genetic knockout of CD38 effectively alleviated neuroinflammation, microglia activation, synaptic defects, and Sirt1/STAT3 signaling, subsequently improving depression-like behaviors. Moreover, optogenetic activation of glutamatergic neurons of hippocampal CA3 reduced the susceptibility of mice to depression-like behaviors, accompanied by reduced CD38 expression. We also found that (R)-ketamine, which displayed antidepressant effects, was linked to its anti-inflammatory properties by suppressing increased CD38 expression and reversing synaptic defects. In conclusion, hippocampal CD38 is closely linked to depression-like behaviors in an inflammation model, highlighting its potential as a therapeutic target for antidepressant development. [ABSTRACT FROM AUTHOR]

Anesthetic ketamine is a racemic mixture containing equal amount of (R)-ketamine and (S)-ketamine. Increasing preclinical data show that (R)-ketamine has a rapid-onset and sustained antidepressant without significant side effects. There are currently many studies on (R)-ketamine, however, the quantity and quality of these studies are unknown. Therefore, we conducted a bibliometric analysis of research on (R)-ketamine from January 2002 to December 2021. We obtained the publications on (R)-ketamine from the Web of Science database during the period. A variety of bibliographic elements were collected, including annual publications, authors, countries/regions, institutions, journals, and keywords. A total of 922 publications were included in this study. Professor Kenji Hashimoto of Chiba University in Japan was the most productively influential author in the field of (R)-ketamine and the authors from United States were the leader in this field. In addition, we found that the antidepressant effect of (R)-ketamine has been a hotspot in very recent years. This study provided a comprehensive analysis of research on (R)-ketamine and highlighted the growing interest in (R)-ketamine and its antidepressant effects. • A total of 922 publications on (R)-ketamine from January 2002 to December 2021 were analyzed. • Professor Kenji Hashimoto of Chiba University was the most productively influential author in the field of (R)-ketamine. • The antidepressant effect of (R)-ketamine has been a hotspot in recent years. [ABSTRACT FROM AUTHOR]