Beneficial effects of arketamine on the reduced bone mineral density in susceptible mice after chronic social defeat stress: Role of the gut-microbiota-bone-brain axis.
Xiayun Wan, Akifumi Eguchi, Lijia Chang, Chisato Mori, Kenji Hashimoto
Neuropharmacology May 1, 2023 DOI: 10.1016/j.neuropharm.2023.109466 via PubMed
Summary
AI-generated from the abstractA single injection of arketamine (10 mg/kg) reduced anhedonia-like behavior and reversed the loss of femoral neck cortical and total bone mineral density in mice susceptible to chronic social defeat stress. The abundance of certain gut microbiota and plasma metabolites differed between arketamine-treated and saline-treated susceptible mice, and these microbial and metabolite abundances correlated with bone mineral density. The findings suggest arketamine may improve both depressive symptoms and bone density through a gut-microbiota-bone-brain axis, indicating potential as a therapy for depressed patients with low bone mineral density.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Chronic social defeat stress susceptible mice |
| Intervention | Arketamine |
| Dose | 10 mg/kg |
| Duration | Single administration |
| Topics | Ketamine |
| Keywords | Bone mineral density Gut microbiota Metabolites |
| Key finding | Arketamine ameliorated anhedonia-like behavior and reduced femoral neck cortical and total bone mineral density in CSDS susceptible mice, with changes linked to gut microbiota and plasma metabolites. |
Abstract
Patients with depression exhibit reduced bone mineral density (BMD). We previously reported that the new antidepressant arketamine improved the reduced BMD seen in chronic social defeat stress (CSDS) susceptible mice and ovariectomized mice. Considering the role of the gut microbiota in maintaining bone health, the current study investigated whether the gut microbiota, along with metabolites derived from the microbiome, play a role in the beneficial actions of arketamine with respect to the anhedonia-like behavior and reduced BMD seen in CSDS susceptible mice. A single administration of arketamine (10 mg/kg) ameliorated anhedonia-like behavior and decreased femoral neck cortical (and total) BMD in CSDS susceptible mice. There was a negative correlation between anhedonia-like behavior and BMD. Furthermore, significant differences in the abundance of microbiota (and plasma metabolites) were found between the CSDS + saline and CSDS + arketamine groups. Correlations were observed between the abundance of certain microbiota (and plasma metabolites) and cortical (and total) BMD. These data suggest that, in addition to its anti-anhedonia effect, arketamine might ameliorate the reduced cortical (and total) BMD seen in CSDS susceptible mice through the gut-microbiota-bone-brain axis. Therefore, arketamine could serve as a drug therapy for depressed patients with low BMD. This article is part of the Special Issue on "Ketamine and its Metabolites".