title: Involvement of normalized NMDA receptor and mTOR-related signaling in rapid antidepressant effects of Yueju and ketamine on chronically stressed mice.
abstract: Yueju, a Traditional Chinese Medicine formula, exhibited fast-onset antidepressant responses similar to ketamine. This study focused on assessing the rapid and persistent antidepressant efficacy of Yueju and ketamine in chronically stressed mice and its association with alternations in prefrontal N-methyl-D-aspartate (NMDA) receptor and mammalian target of rapamycin (mTOR)-related activity. Chronic mild stress (CMS) led to deficits in sucrose preference test (SPT), forced swim test, tail suspension test, and novelty-suppressed feeding test, which were improved differently by acute Yueju or ketamine administration. The improvement in SPT started as soon as 2 hours post Yueju and ketamine but lasted for 6 days only by Yueju. Body weight was regained by Yueju more than ketamine at post-drug administration day (PAD) 6. CMS decreased phosphorylation of the mTOR effectors 4E-BP1 and p70S6K, their upstream regulators ERK and Akt, and downstream targets including synaptic protein GluR1. Yueju or ketamine reversed these changes at PAD 2, but only Yueju reversed phosphor-Akt at PAD 6. CMS selectively and lastingly increased NMDA receptor subunit NR1 expression, which was reversed by ketamine or Yueju at PAD 2 but only by Yueju at PAD 6. These findings suggest that NR1 and Akt/mTOR signaling are important therapeutic targets for depression.
authors: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Key Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Physiology Research Section, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Juanjuan
authors: J
authors: Tang
authors: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Key Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Wenda
authors: W
authors: Xue
authors: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Key Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Baomei
authors: B
authors: Xia
authors: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Key Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Li
authors: L
authors: Ren
authors: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Key Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Weiwei
authors: W
authors: Tao
authors: First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Chang
authors: C
authors: Chen
authors: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Key Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Hailou
authors: H
authors: Zhang
authors: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Key Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Ruyan
authors: R
authors: Wu
authors: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Key Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Qisheng
authors: Q
authors: Wang
authors: Key Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Haoxin
authors: H
authors: Wu
authors: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Key Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Jinao
authors: J
authors: Duan
authors: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Key Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Gang
authors: G
authors: Chen
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal; D002908:Chronic Disease; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008954:Models, Biological; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D004365:Drugs, Chinese Herbal; D021122:Protein Subunits; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C531537:Yueju-Wan; D007649:Ketamine; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases