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. (1st May 2023)

• Record Type: Journal Article
• Authors: Wan, Xiayun; Eguchi, Akifumi; Chang, Lijia; Mori, Chisato; Hashimoto, Kenji
• Is Part Of: Neuropharmacology. Volume 228(2023)
• Publication Date: 2023-05-01
• Subjects: Arketamine -- Bone -- Bone mineral density -- Gut microbiota -- Metabolites; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2023.109466
• Languages: English
• ISSNs: 0028-3908

Abstract

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". Graphical abstract: Image 1 Highlights: Patients with depression exhibit reduced bone mineral density (BMD). Susceptible mice after chronic social defeat stress (CSDS) exhibit reduced BMD. Arketamine ameliorated anhedonia-like behavior and reduced BMD in CSDS susceptible mice. There were correlations between the abundance of certain microbiota 8and plasma metabolites) and BMD. Arketamine would be a therapeutic drug for depressed patients with low BMD.