Ketamine is a noncompetitive antagonist of N-methyl-D-aspartate receptors (NMDARs). We have shown that ketamine can induce cognitive impairments and schizophrenia-like symptoms in mice. However, the detailed metabolic profile changes in the progression of ketamine-induced schizophrenia-like symptoms are still not fully elucidated. In this study, an ultra-performance liquid chromatography-Q-Exactive hybrid quadrupole-Orbitrap mass spectrometry-based untargeted hippocampus high-throughput metabolomics method was first performed to screen for potential biomarkers in a schizophrenia-like state in a chronically administered ketamine-induced mouse model. Our results identified that the amino acid and energy metabolism pathways were significantly affected in mouse models of ketamine-induced schizophrenia. The detailed amino acid profiles were subsequently quantified in the hippocampus. The results showed that ketamine dramatically decreased the Lys, Gly, and Ser levels while significantly increasing the Gln level and relative Glu-to-GABA ratio. Our study suggested that Gln, Gly and Ser metabolism disturbances might be involved in ketamine-induced schizophrenia-like phenotypes. This research offers a fresh viewpoint for creating new neuroleptic medications and contributes to understanding the mechanisms underlying ketamine-induced schizophrenia.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2022.09.064 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ketamine administration during adolescence impairs synaptic integration and inhibitory synaptic transmission in the adult dentate gyrus.
Prog Neurobiol
January 2025
Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Universidad de Valparaíso, Valparaíso 2340000, Chile; Millennium Nucleus of Neuroepigenetics and Plasticity (EpiNeuro), Santiago, Chile. Electronic address:
Ketamine administration during adolescence affects cognitive performance; however, its long-term impact on synaptic function and neuronal integration in the hippocampus a brain region critical for cognition remains unclear. Using functional and molecular analyses, we found that chronic ketamine administration during adolescence exerts long-term effects on synaptic integration, expanding the temporal window in an input-specific manner affecting the inner molecular layer but not the medial perforant path inputs in the adult mouse dorsal hippocampal dentate gyrus. Ketamine also alters the excitatory/inhibitory balance by reducing the efficacy of inhibitory inputs likely due to a reduction in parvalbumin-positive interneurons number and function.
View Article and Find Full Text PDFRepeated administration of a subanesthetic dose of ketamine results in impaired motor and cognitive behavior and differential expression of hippocampal P2X1 and P2X7 receptors in adult mice.
Behav Brain Res
January 2025
Laboratorio de Neurobiología, División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica (IPICYT), San Luis Potosí, Mexico. Electronic address:
Ketamine hydrochloride serves multiple purposes, including its use as a general anesthetic, treatment for depression, and recreational drug. In studies involving rodents, ketamine is utilized as a model for schizophrenia. However, it is unclear whether age affects the behavioral response induced by repeated ketamine administration and if it modifies the expression levels of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and purinergic receptors (P2X1, P2X4, P2X7).
View Article and Find Full Text PDFExploring the Different Impacts of Ketamine on Neurotrophic Factors and Inflammatory Parameters in a Cecal Ligation and Puncture-Induced Sepsis Model.
Neurotox Res
January 2025
Translational Psychiatry Laboratory, Graduate Program in Health Sciences, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC, Brazil.
Given ketamine's conflicting impacts on the central nervous system, investigating its effects within an inflammatory context becomes crucial. This study aimed to assess the impact of varying ketamine doses on neurotrophin and inflammatory cytokine levels within the brains of rats submitted to the sepsis model. Wistar rats were submitted to the cecal ligation and puncture (CLP) model of sepsis.
View Article and Find Full Text PDFInulin alleviates chronic ketamine-induced impairments in memory and prepulse inhibition by regulating the gut microbiota, inflammation, and kynurenine pathway.
Int J Biol Macromol
January 2025
Institute of Neuropsychiatry, The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Liwan District, Guangzhou, Guangdong Province 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China. Electronic address:
Chronic ketamine administration causes cognitive impairments similar to those observed in schizophrenia. Growing evidence suggests that patients with schizophrenia show alterations in gut microbiota, which is associated with cognitive impairments. Inulin could regulate gut microbiota.
View Article and Find Full Text PDFChelidonic acid abrogates oxidative stress and memory dysfunction in experimental aging rats.
Turk J Biol
October 2024
Neuropyschopharmacology Application and Research Center, Üsküdar University, İstanbul, Turkiye.
Background/aim: In an aging model established using male Wistar albino rats via the administration of D-galactose (D-gal), the aim of this study was to examine the effects of chelidonic acid (CA) on cognitive function and the levels of glutathione (GSH), malondialdehyde (MDA), total antioxidant status (TAS), and brain-derived neurotrophic factor (BDNF).
Materials And Methods: Thirty-two, three-month-old Wistar albino male rats (n = 8) were divided into four groups, as the control (C) group, CA group (2 mg/kg of CA via oral gavage), D-gal group (150 mg/kg of D-gal, subcutaneously), and D-gal + CA group (150 mg/kg of D-gal and 2 mg/kg of CA). Following overnight fasting, the 10-week trial was concluded with intramuscular injections of anesthetic drugs xylazine (8-10 mg/kg) and ketamine (80-100 mg/kg), and subsequently, the collection of cardiac blood.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!