Niannian Huang1, Yue Wang1, Gaofeng Zhan1, Fan Yu2, Shan Li1, Dongyu Hua1, Riyue Jiang3, Shiyong Li1, Yeshun Wu4, Ling Yang4, Bin Zhu5, Fei Hua2, Ailin Luo6, Chun Yang7. 1. Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. 2. Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China. 3. Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China. 4. Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China. 5. Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China. 6. Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. alluo@tjh.tjmu.edu.cn. 7. Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. yangchuntz@sina.com.
Abstract
RATIONALE: Basic and clinical studies have reported rapid and long-lasting antidepressant effects of ketamine. Although previous studies have proposed several mechanisms underlying the antidepressant effects of ketamine, these mechanisms have not been completely elucidated. OBJECTIVES: The present study evaluated the effects of systemically administered ketamine treatment in a lipopolysaccharide (LPS)-induced mouse model of depression. METHODS: Non-targeted metabolomics, western blotting, and behavioral tests (locomotion, tail suspension, and forced swimming tests) were performed. RESULT: Ketamine significantly attenuated the abnormally increased immobility time in a lipopolysaccharide (LPS)-induced mouse model of depression. Aminomalonic acid, glutaraldehyde, glycine, histidine, N-methyl-L-glutamic acid, and ribose levels in skeletal muscle were altered following ketamine administration. Furthermore, ketamine significantly decreased the LPS-induced increase in glycine receptor A1 (GlyA1) levels. However, the glycine receptor antagonist strychnine did not elicit any pharmacological effects on ketamine-induced alterations in behaviors or muscular GlyA1 levels. Exogenous glycine and L-serine significantly improved depression-like symptoms in LPS-induced mice. CONCLUSIONS: Our findings suggest that skeletal muscular glycine contributes to the antidepressant effects of ketamine in inflammation. Effective strategies for improving skeletal muscular glycine levels may be a novel approach to depression treatment.
RATIONALE: Basic and clinical studies have reported rapid and long-lasting antidepressant effects of ketamine. Although previous studies have proposed several mechanisms underlying the antidepressant effects of ketamine, these mechanisms have not been completely elucidated. OBJECTIVES: The present study evaluated the effects of systemically administered ketamine treatment in a lipopolysaccharide (LPS)-induced mouse model of depression. METHODS: Non-targeted metabolomics, western blotting, and behavioral tests (locomotion, tail suspension, and forced swimming tests) were performed. RESULT: Ketamine significantly attenuated the abnormally increased immobility time in a lipopolysaccharide (LPS)-induced mouse model of depression. Aminomalonic acid, glutaraldehyde, glycine, histidine, N-methyl-L-glutamic acid, and ribose levels in skeletal muscle were altered following ketamine administration. Furthermore, ketamine significantly decreased the LPS-induced increase in glycine receptor A1 (GlyA1) levels. However, the glycine receptor antagonist strychnine did not elicit any pharmacological effects on ketamine-induced alterations in behaviors or muscular GlyA1 levels. Exogenous glycine and L-serine significantly improved depression-like symptoms in LPS-induced mice. CONCLUSIONS: Our findings suggest that skeletal muscular glycine contributes to the antidepressant effects of ketamine in inflammation. Effective strategies for improving skeletal muscular glycine levels may be a novel approach to depression treatment.
Authors: Leandro Z Agudelo; Teresa Femenía; Funda Orhan; Margareta Porsmyr-Palmertz; Michel Goiny; Vicente Martinez-Redondo; Jorge C Correia; Manizheh Izadi; Maria Bhat; Ina Schuppe-Koistinen; Amanda T Pettersson; Duarte M S Ferreira; Anna Krook; Romain Barres; Juleen R Zierath; Sophie Erhardt; Maria Lindskog; Jorge L Ruas Journal: Cell Date: 2014-09-25 Impact factor: 41.582
Authors: Yi Nong; Yue-Qiao Huang; William Ju; Lorraine V Kalia; Gholamreza Ahmadian; Yu Tian Wang; Michael W Salter Journal: Nature Date: 2003-03-20 Impact factor: 49.962