title: Instant and Lasting Down-Regulation of NR1 Expression in the Hippocampus is Associated Temporally with Antidepressant Activity After Acute Yueju.
abstract: Accumulating evidence indicated that N-methyl-D-aspartate (NMDA) receptors are involved in the pathophysiology of depression and implicated in therapeutic targets. NMDA antagonists, such as ketamine, displayed fast-onset and long-lasting antidepressant activity in preclinical and clinical studies. Previous studies showed that Yueju pill exerts antidepressant effects similar to ketamine. Here, we focused on investigating the association of acute and lasting antidepressant responses of Yueju with time course changes of NMDA receptor subunits NR1, NR2A, and NR2B expressions in the hippocampus, a key region regulating depression response. As a result, Yueju reduced immobility time in the forced swimming test from 30 min to 5 days post a single administration. Yueju acutely decreased NR1 and NR2B protein expression in the hippocampus, with NR2A expression unaltered. NR1 expression remained down-regulated 5 days post Yueju administration, whereas NR2B returned to normal level in 24 h. Yueju and ketamine similarly ameliorated the depression-like symptoms at least for 72 h in learned helplessness test. They both reversed the up-regulated expression of NR1 in the learned helpless mice 1 or 3 days post administration. Different from ketamine, the antidepressant effects of Yueju were not influenced by blockade of amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor. These findings served as preclinical evidence that Yueju may confer acute and long-lasting antidepressant effects by favorably modulating NMDA function in the hippocampus.
authors.affiliation: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Baomei
authors.initials: B
authors.lastname: Xia
authors.affiliation: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Hailou
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Wenda
authors.initials: W
authors.lastname: Xue
authors.affiliation: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Tao
authors.affiliation: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.affiliation: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Ruyan
authors.initials: R
authors.lastname: Wu
authors.affiliation: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.affiliation: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Key Laboratory of Integrative Medicine for 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.forename: Juanjuan
authors.initials: J
authors.lastname: Tang
authors.affiliation: Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Haoxin
authors.initials: H
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Baochang
authors.initials: B
authors.lastname: Cai
authors.affiliation: School of Behavioral Sciences, The Academic College of Tel Aviv-Yaffo, Tel-Aviv, 61083, Israel.
authors.forename: Ravid
authors.initials: R
authors.lastname: Doronc
authors.affiliation: Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China. chengang@njucm.edu.cn.|Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China. chengang@njucm.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy*; D003866:Depressive Disorder / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine
keywords: GluA1; Ketamine; Learned helplessness; NMDA receptor; NR1; Yueju pill
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