Depression-like phenotypes in mice with hepatic ischemia/reperfusion injury: A role of gut-microbiota-liver-brain axis via vagus nerve.
Yong Yang, Akifumi Eguchi, Xiayun Wan, Chisato Mori, Kenji Hashimoto
Journal of Affective Disorders January 15, 2024 DOI: 10.1016/j.jad.2023.10.142 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice with hepatic ischemia/reperfusion injury |
| Intervention | Arketamine |
| Dose | single injection |
| Duration | Behavioral tests 7 days after surgery; single injection of arketamine after behavioral tests |
| Topics | Depression Ketamine |
| Keywords | Gut microbiota Liver Metabolites Vagus nerve |
| Key points | Hepatic ischemia/reperfusion injury induces depression-like phenotypes in mice through the gut-microbiota-liver-brain axis via the subdiaphragmatic vagus nerve, and arketamine ameliorates these phenotypes. |
Abstract
Depression is a frequent symptom in patients with chronic liver disease; however, the mechanisms underlying this association remain unclear. Dysbiosis of gut microbiota plays a critical role in depression through the gut-brain axis via the vagus nerve. In this study, we investigated whether the gut-microbiota-liver-brain axis plays a role in depression-like phenotypes in mice with hepatic ischemia/reperfusion (HI/R) injury via the vagus nerve. Behavioral tests for depression-like behaviors were performed 7 days after sham or HI/R injury surgery. Mice with HI/R injury exhibited splenomegaly, systemic inflammation, depression-like behaviors, reduced expression of synaptic proteins in the prefrontal cortex (PFC), abnormal composition of gut microbiota, and altered blood metabolites and lipids. Furthermore, there were positive or negative correlations between the relative abundance of microbiome and behavioral data or blood metabolites (or lipids). Moreover, subdiaphragmatic vagotomy significantly blocked these changes in mice with HI/R injury. Notably, depression-like phenotypes in mice with HI/R injury were ameliorated after subsequent single injection of the new antidepressant arketamine. The current findings suggest that HI/R injury induces depression-like phenotypes in mice through the gut-microbiota-liver-brain axis via the subdiaphragmatic vagus nerve. Furthermore, arketamine may have therapeutic potential in the treatment of depression in patients with chronic liver disease.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cited by 4
- Role of the gut-brain axis via the subdiaphragmatic vagus nerve in stress resilience of 3,4-methylenedioxymethamphetamine in mice exposed to chronic restrain stress. Neurobiology of Disease December 1, 2023
- Role of oxidative phosphorylation in the antidepressant effects of arketamine via the vagus nerve-dependent spleen-brain axis. Neurobiology of Disease September 1, 2024
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers. Journal of Anesthesia and Translational Medicine September 1, 2025
- Depression-like phenotypes in mice following common bile duct ligation: Insights into the gut-liver-brain axis via the vagus nerve. Neurobiology of Disease March 1, 2024
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