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Rapid Antidepressant-Like Potential of Chaihu Shugan San Depends on Suppressing Glutamate Neurotransmission and Activating Synaptic Proteins in Hippocampus of Female Mice

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Abstract

Objective

To explore the rapid antidepressant potential and the underlying mechanism of Chaihu Shugan San (CSS) in female mice.

Methods

Liquid chromatography mass spectrometry (LC-MS)/MS was used to determine the content of main components in CSS to determine its stability. Female C57BL/6J mice were randomly divided into 4 groups, including control (saline), vehicle (saline), CSS (4 g/kg) and ketamine (30 mg/kg) groups. Mice were subjected to irregular stress stimulation for 4 weeks to establish the chronic mild stress (CMS) model, then received a single administration of drugs. Two hours later, the behavioral tests were performed, including open field test, tail suspension test (TST), forced swimming test (FST), novelty suppression feeding test (NSF), and sucrose preference test (SPT). Western blot analysis was used to detect the expression levels of N-methyl-D-aspartate receptor (NMDA) subtypes [N-methyl-D-aspartate receptor 1 (NR1), NR2A, NR2B], synaptic proteins [synapsin1 and post synaptic density protein 95 (PSD95)], and brain-derived neurotrophic factor (BDNF). Moreover, the rapid antidepressant effect of CSS was tested by pharmacological technologies and optogenetic interventions that activated glutamate receptors, NMDA.

Results

Compared with the vehicle group, a single administration of CSS (4 g/kg) reversed all behavioral defects in TST, FST, SPT and NSF caused by CMS (P<0.05 or P<0.01). CSS also significantly decreased the expressions of NMDA subtypes (NR1, NR2A, NR2B) at 2 h in hippocampus of mice (all P<0.01). In addition, similar to ketamine, CSS increased levels of synaptic proteins and BDNF (P<0.05 or P<0.01). Furthermore, the rapid antidepressant effects of CSS were blocked by transient activation of NMDA receptors in the hippocampus (all P<0.01).

Conclusion

Rapid antidepressant effects of CSS by improving behavioral deficits in female CMS mice depended on rapid suppression of NMDA receptors and activation of synaptic proteins.

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Authors and Affiliations

  1. Department of Chinese Medicine Preparations, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China

    Chao Lu, Zi-wei Gao, Shan Xing, Hui-hui Wang, Hang Zhou & Lei Wu

  2. College of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210046, China

    Shan Xing

  3. Department of Chinese Medicine, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China

    Yun-ke Huang

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  1. Chao Lu
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  2. Zi-wei Gao
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  4. Hui-hui Wang
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  5. Yun-ke Huang
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  6. Hang Zhou
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  7. Lei Wu
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Contributions

Lu C, Gao ZW and Wu L conceived and designed the experiments. Wu L, Gao ZW, Huang YK, Lu C, and Wang HH performed the experiments. Wu L, Lu C and Zhou H analyzed the data. Lu C, Xing S and Wu L contributed to the writing of the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Lei Wu.

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The authors declare no competing financial interest.

Additional information

Supported by the National Natural Science Foundation of China (No. 82174107, 82304898), Jiangsu Provincial Administration of Traditional Chinese Medicine Fund (No. YB2020014), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (No. 035062005001)

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Lu, C., Gao, Zw., Xing, S. et al. Rapid Antidepressant-Like Potential of Chaihu Shugan San Depends on Suppressing Glutamate Neurotransmission and Activating Synaptic Proteins in Hippocampus of Female Mice. Chin. J. Integr. Med. (2024). https://doi.org/10.1007/s11655-024-3906-2

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