Skip to content

Mapping metabolite change in the mouse brain after esketamine injection by ambient mass spectrometry imaging and metabolomics.

Guan-Xi Liu, Ze-Lin Li, Su-Yan Lin, Qian Wang, Zheng-Yi Luo, Kai Wu, Yan-Lin Zhou, Yu-Ping Ning

Frontiers in Psychiatry May 10, 2023 DOI: 10.3389/fpsyt.2023.1109344 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Preclinical spatial metabolomics study Peer reviewed
Population Brain tissue (whole-brain metabolic mapping in an animal model after esketamine injection)
Intervention Esketamine
Topics Depression Ketamine Esketamine
Keywords Antidepressant Mass spectrometry imaging Spatial metabolomics
Key points Using AFADESI-mass spectrometry imaging, the authors report that esketamine injection produced metabolite changes across the brain, with glycerophospholipid metabolism altered mainly around the brain and sphingolipid metabolism altered mainly in the globus pallidus, the region showing the most significant metabolite change. They propose this spatial metabolic mapping helps explore esketamine's potential antidepressant mechanism.

Abstract

Ketamine is a new, fast, and effective antidepression treatment method; however, the possible dissociation effects, sensory changes, abuse risk, and the inability to accurately identify whether patients have a significant response to ketamine limit its clinical use. Further exploration of the antidepressant mechanisms of ketamine will contribute to its safe and practical application. Metabolites, the products of upstream gene expression and protein regulatory networks, play an essential role in various physiological and pathophysiological processes. In traditional metabonomics it is difficult to achieve the spatial localization of metabolites, which limits the further analysis of brain metabonomics by researchers. Here, we used a metabolic network mapping method called ambient air flow-assisted desorption electrospray ionization (AFADESI)-mass spectrometry imaging (MSI). We found the main changes in glycerophospholipid metabolism around the brain and sphingolipid metabolism changed mainly in the globus pallidus, which showed the most significant metabolite change after esketamine injection. The spatial distribution of metabolic changes was evaluated in the whole brain, and the potential mechanism of esketamine's antidepressant effect was explored in this research.

Comparable studies

Other preclinical and animal studies on esketamine for depression, most cited first.

Study Year Design Participants
Low-dose S-ketamine exerts antidepressant-like effects via enhanced hippocampal synaptic plasticity in postpartum depression rats. Rat model of postpartum depression induced by reproductive hormone withdrawal 2022 Animal study
Antidepressant effects of esketamine via the BDNF/AKT/mTOR pathway in mice with postpartum depression and their offspring. Mice with postpartum depression and their offspring 2024 Animal study
Electroconvulsive therapy combined with esketamine improved depression through PI3K/AKT/GLT-1 pathway. Human patients with severe depression and a rat model of depression 2025 Randomized controlled trial and animal study n = 12
S-ketamine Alleviates Neuroinflammation and Attenuates Lipopolysaccharide-Induced Depression Via Targeting SIRT2. Lipopolysaccharide (LPS)-induced mouse model 2025 Animal study with in vitro and in vivo experiments
Esketamine alleviates LPS-induced depression-like behavior by activating Nrf2-mediated anti-inflammatory response in adolescent mice. Adolescent male C57BL/6J mice 2025 Preclinical experimental study

Explore topics

By condition and practice