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Instant and Lasting Down-Regulation of NR1 Expression in the Hippocampus is Associated Temporally with Antidepressant Activity After Acute Yueju

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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.

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Acknowledgments

This study was supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the Natural Science Foundation of Jiangsu Province (Grant Nos. BK20140962, BK20151568), the Natural Science Foundation of Nanjing University of Chinese Medicine (Grant Nos. 12XZR03, 12XZR04), the Israel Science Foundation (ISF 738/11), and Jiangsu Province college student’s practice and innovation training (201310315007Z).

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Authors and Affiliations

  1. Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China

    Baomei Xia, Hailou Zhang, Wenda Xue, Weiwei Tao, Chang Chen, Ruyan Wu, Li Ren, Juanjuan Tang & Gang Chen

  2. Key Laboratory of Integrative Medicine for Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China

    Baomei Xia, Hailou Zhang, Wenda Xue, Weiwei Tao, Chang Chen, Ruyan Wu, Li Ren, Juanjuan Tang, Haoxin Wu & Gang Chen

  3. Physiology Research Section, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China

    Juanjuan Tang

  4. First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China

    Chang Chen

  5. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China

    Baochang Cai

  6. School of Behavioral Sciences, The Academic College of Tel Aviv-Yaffo, Tel-Aviv, 61083, Israel

    Ravid Doronc

Authors
  1. Baomei Xia
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  2. Hailou Zhang
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  3. Wenda Xue
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  4. Weiwei Tao
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  5. Chang Chen
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  7. Li Ren
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  8. Juanjuan Tang
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  9. Haoxin Wu
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  10. Baochang Cai
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  11. Ravid Doronc
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  12. Gang Chen
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Correspondence to Gang Chen.

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Xia, B., Zhang, H., Xue, W. et al. Instant and Lasting Down-Regulation of NR1 Expression in the Hippocampus is Associated Temporally with Antidepressant Activity After Acute Yueju. Cell Mol Neurobiol 36, 1189–1196 (2016). https://doi.org/10.1007/s10571-015-0316-1

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  • DOI: https://doi.org/10.1007/s10571-015-0316-1

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