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Microglia-Dependent Reversal of Depression-Like Behaviors in Chronically Stressed Mice by Administration of a Specific Immuno-stimulant β-Glucan

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Abstract

In recent years, the decline of microglia in the hippocampus has been shown to play a role in the development of depression, and its reversal shows marked antidepressant-like effects. β-glucan is a polysaccharide from Saccharomyces cerevisiae and has numerous beneficial effects on the nervous system, including improving axon regeneration and cognition. Considering its immuno-stimulatory activities in cultured microglia and brain tissues, we hypothesize that β-glucan may be a potential candidate to correct the functional deficiency of microglia and thereby alleviate depression-like behaviors in chronically stressed animals. An expected, our results showed that a single injection of β-glucan 5 h before behavioral tests at a dose of 10 or 20 mg/kg, but not at a dose of 5 mg/kg, reversed the depression-like behavior induced by chronic stress in mice in the tail suspension test, forced swimming test, and sucrose preference test. The effect of β-glucan (20 mg/kg) also showed time-dependent properties that were statistically significant 5 and 8, but not 3, hours after drug injection and persisted for at least 7 days. Fourteen days after β-glucan injection, no antidepressant-like effect was observed anymore. However, this effect was overcome by a second β-glucan injection (20 mg/kg) 14 days after the first β-glucan injection. Stimulation of microglia appeared to mediate the antidepressant-like effect of β-glucan, because both inhibition of microglia and their depletion prevented the antidepressant-like effect of β-glucan. Based on these effects of β-glucan, β-glucan administration could be developed as a new strategy for the treatment of depression.

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Acknowledgements

The authors would kindly like to thank Dr Yiming Gu for his initial contribution to the construction of the depression model.

Funding

This work was supported by the Natural Science Foundation of Jiangsu Province (BK20221375 and BK20230288), the Nantong Health Commission (QN2023035 and MS2023033), the Six Phase of Jiangsu 333 High-level Talent Training Project (2022: 3-16-661), and the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province (23KJB310020).

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Author notes

  1. Cheng Zhao, Zhuo Chen, Xu Lu, Wenfeng Hu and Rongrong Yang have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Affiliated Hospital of Nantong University, #20 Xisi Road, Nantong, 226001, Jiangsu, China

    Cheng Zhao

  2. Invasive Technology Department, First People’s Hospital of Nantong City, the Second Affiliated Hospital of Nantong University, #666 Shengli Road, Nantong, 226006, China

    Zhuo Chen

  3. Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong, 226001, Jiangsu Province, China

    Xu Lu, Bingran Chen & Chao Huang

  4. Department of Pharmacy, Affiliated Maternal and Child Health Hospital of Nantong University, #399 Shijidadao, Nantong, 226007, China

    Wenfeng Hu

  5. Department of Anesthesiology, Affiliated Hospital of Nantong University, #20 Xisi Road, Nantong, 226001, Jiangsu, China

    Rongrong Yang

  6. Department of Pharmacy, Nantong Third Hospital Affiliated to Nantong University, #60 Middle Qingnian Road, Nantong, 226006, Jiangsu, China

    Qun Lu

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  1. Cheng Zhao
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Contributions

CZ: Methodology, Software, Investigation, Formal analysis, Writing—original draft. ZC: Methodology, Software. QL: Methodology, Software, Investigation, Formal analysis, Data curation. XL: Methodology, Resources, Supervision. WH: Methodology, Software. Rongrong Yang: Methodology, Software. BC: Methodology, Software. CH: Conceptualization, Resources, Supervision. All authors reviewed and approved the manuscript.

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Correspondence to Cheng Zhao or Chao Huang.

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Zhao, C., Chen, Z., Lu, X. et al. Microglia-Dependent Reversal of Depression-Like Behaviors in Chronically Stressed Mice by Administration of a Specific Immuno-stimulant β-Glucan. Neurochem Res 49, 519–531 (2024). https://doi.org/10.1007/s11064-023-04056-x

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