The role of CD38 in inflammation-induced depression-like behavior and the antidepressant effect of (R)-ketamine.
Xinying Zhang, Teng He, Zifeng Wu, Yuanyuan Wang, Hanyu Liu, Bingyuan Zhang, Siqi Yang, Di Wang, Chao Huang, J. Duan, Xiangyang Xu, Xiangqing Xu, Kenji Hashimoto, Riyue Jiang, Ling Yang, Chun Yang
Brain, behavior, and immunity October 1, 2023 DOI: 10.1016/j.bbi.2023.09.026 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | LPS-treated mice |
| Interventions | genetic knockout of CD38 (R)-ketamine |
| Topics | Depression Esketamine Ketamine |
| Key points | Hippocampal CD38 expression is linked to depression-like behaviors in an inflammation model, and its inhibition alleviates these behaviors. |
Abstract
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 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 depressive behaviors in an inflammation model, highlighting its potential as a therapeutic target for antidepressant development.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.