Skip to main content
SpringerLink
Log in

Atractylenolide I Suppresses A1 Astrocyte Activation to Improve Depression in Mice

  • Original Article
  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

This work aimed to investigate the role of atractylenolide I (ATR) in resisting depression and its mechanism of action. The mouse model of depression was constructed through chronic unpredictable mild stress (CUMS) method. After ATR intervention, changes in the depression-related behaviors of mice were detected through open field test and elevated plus maze. In addition, enzyme-linked immunosorbent assay (ELISA) was conducted to detect inflammatory factor levels. Real-time fluorescence quantitative PCR (RT-qPCR) was performed to measure the mRNA levels of A1/A2 astrocyte markers. Furthermore, primary astrocytes were induced in vitro, and the A1 differentiation level was detected by ELISA and RT-qPCR assays. ATR improved the behaviors of CUMS mice and alleviated the depression symptoms. Moreover, it reduced tissue inflammation, inhibited the A1 differentiation of astrocytes, and decreased the mRNA levels of A1 markers. After NLRP3 knockout, the effects of ATR were suppressed. Similarly, in vitro experimental results also revealed that ATR suppressed the A1 differentiation of astrocytes. Based on molecular dynamics and small molecule-protein docking results, ATR mainly targeted NLRP3 and suppressed the NLRP3-mediated A1 differentiation. We discover that ATR can target NLRP3 to suppress A1 differentiation of astrocytes, restrain tissue inflammation, and improve the depression symptoms in mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35

    Article  PubMed  Google Scholar 

  2. Liddelow S, Barres B (2015) SnapShot: astrocytes in health and disease. Cell 162:1170-1170.e1171

    Article  CAS  PubMed  Google Scholar 

  3. Eng L, Vanderhaeghen J, Bignami A et al (1971) An acidic protein isolated from fibrous astrocytes. Brain Res 28:351–354

    Article  CAS  PubMed  Google Scholar 

  4. Hara M, Kobayakawa K, Ohkawa Y et al (2017) Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin-N-cadherin pathway after spinal cord injury. Nat Med 23:818–828

    Article  CAS  PubMed  Google Scholar 

  5. Myer DJ (2006) Essential protective roles of reactive astrocytes in traumatic brain injury. Brain 129:2761–2772

    Article  CAS  PubMed  Google Scholar 

  6. Liddelow SA, Barres BA (2017) Reactive astrocytes: production, function, and therapeutic potential. Immunity 46:957–967

    Article  CAS  PubMed  Google Scholar 

  7. Liddelow SA, Guttenplan KA, Clarke LE et al (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541:481–487

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zamanian JL, Xu L, Foo LC et al (2012) Genomic analysis of reactive astrogliosis. J Neurosci 32:6391–6410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hou B, Zhang Y, Liang P, He Y, Peng B, Liu W, Han S, Yin J et al (2020) Inhibition of the NLRP3-inflammasome prevents cognitive deficits in experimental autoimmune encephalomyelitis mice via the alteration of astrocyte phenotype. Cell Death Dis 11(5):377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Endo K, Taguchi T, Taguchi F et al (1979) Antiinflammatory principles of Atractylodes rhizomes. Chem Pharm Bull (Tokyo) 27(12):2954–2958

    Article  CAS  PubMed  Google Scholar 

  11. Kitajima J, Kamoshita A, Ishikawa T et al (2003) Glycosides of Atractylodes ovata. Chem Pharm Bull (Tokyo) 51(9):1106–1108

    Article  CAS  PubMed  Google Scholar 

  12. Cheng Y, Mai JY, Hou TL et al (2016) Antiviral activities of atractylon from Atractylodis Rhizoma. Mol Med Rep 14(4):3704–3710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Iamsaard S, Kietinun S, Sattayasai J, Bunluepuech K, Wu AT, Choowong-In P (2023) Prevention of seminal vesicle damage by Mucuna pruriens var. pruriens seed extract in chronic unpredictable mild stress mice. Pharm Biol. 61(1):89–99

    Article  CAS  PubMed  Google Scholar 

  14. Hammond TR, McEllin B, Morton PD et al (2015) Endothelin-B receptor activation in astrocytes regulates the rate of oligodendrocyte regeneration during remyelination. Cell Rep 13:2090–2097

    Article  CAS  PubMed  Google Scholar 

  15. Faulkner JR, Herrmann JE, Woo MJ et al (2004) Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 24:2143–2155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bélanger M, Magistretti PJ (2009) The role of astroglia in neuroprotection. Dialogues Clin Neurosci 11:281–295

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zhong Z, Wen Z, Darnell JE Jr (1994) Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264:95–98

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Hong S, Song MR (2014) STAT3 but not STAT1 is required for astrocyte differentiation. PLoS ONE 9:e86851

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  19. Anderson MA, Burda JE, Ren Y et al (2016) Astrocyte scar formation aids central nervous system axon regeneration. Nature 532:195–200

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kettenmann H, Verkhratsky A (2008) Neuroglia: the 150 years after. Trends Neurosci 31:653–659

    Article  CAS  PubMed  Google Scholar 

  21. Okada S, Nakamura M, Katoh H et al (2006) Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nature Med 12:829–834

    Article  CAS  PubMed  Google Scholar 

  22. Kowiański P, Lietzau G, Czuba E et al (2018) BDNF: a key factor with multipotent impact on brain signaling and synaptic plasticity. Cell Mol Neurobiol 38:579–593

    Article  PubMed  Google Scholar 

  23. Xu X, Zhang A, Zhu Y et al (2018) MFG-E8 reverses microglial-induced neurotoxic astrocyte (A1) via NF-κ B and PI3K-Akt pathways. J Cell Physiol 234:904–914

    Article  PubMed  Google Scholar 

  24. Fujita A, Yamaguchi H, Yamasaki R et al (2018) Connexin 30 deficiency attenuates A2 astrocyte responses and induces severe neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride Parkinson’s disease animal model. J Neuroinflammation 15:227

    Article  PubMed  PubMed Central  Google Scholar 

  25. Zhang L, Lei Z, Guo Z et al (2020) Development of neuroregenerative gene therapy to reverse glial scar tissue back to neuron-enriched tissue. Front Cell Neurosci 14:594170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ma M, Li H, Wu J et al (2020) Roles of prokineticin 2 in subarachnoid hemorrhage-induced early brain injury via regulation of phenotype polarization in astrocytes. Mol Neurobiol 57:3744–3758

    Article  CAS  PubMed  Google Scholar 

  27. Liu LR, Liu JC, Bao JS et al (2020) Interaction of microglia and astrocytes in the neurovascular unit. Front Immunol 11:1024

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

I need to thank my colleagues and friends for their help and support in the research. Thanks for the support of the Science and Technology Planning Project of Jiaxing.

Funding

This study is funded by the Science and Technology Planning Project of Jiaxing [2023AZ11001].

Author information

Authors and Affiliations

  1. Department of Neurology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China

    Liping Zhai

  2. The Second Affiliated Hospital of Jiaxing University, Jiaxing, China

    Yongjia Sheng, Jin Wang, Xiaohong Zhou, Wenyan Li, Shasha Wu & Yi Yang

Authors
  1. Liping Zhai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yongjia Sheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaohong Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenyan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shasha Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Liping Zhai and Yongjia Sheng: Responsible for the operation of animal experiments and cell experiments. Jin Wang and Xiaohong Zhou: Responsible for data analysis and chart production. Wenyan Li and Shasha Wu: Responsible for writing and revising articles. Yi Yang: Provide funding and guidance for project implementation.

Corresponding author

Correspondence to Yi Yang.

Ethics declarations

Ethical Approval and Consent to Participate

The study is approved by the Ethics Committee.

Consent for Publication

All authors approved to publish the article.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhai, L., Sheng, Y., Wang, J. et al. Atractylenolide I Suppresses A1 Astrocyte Activation to Improve Depression in Mice. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04025-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12035-024-04025-7

Keywords

Search

Navigation