Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Gut microbiota-induced CXCL1 elevation triggers early neuroinflammation in the substantia nigra of Parkinsonian mice

Acta Pharmacologica Sinica volume 45, pages 52–65 (2024)Cite this article

Abstract

Gut microbiota disturbance and systemic inflammation have been implicated in the degeneration of dopaminergic neurons in Parkinson’s disease (PD). How the alteration of gut microbiota results in neuropathological events in PD remains elusive. In this study, we explored whether and how environmental insults caused early neuropathological events in the substantia nigra (SN) of a PD mouse model. Aged (12-month-old) mice were orally administered rotenone (6.25 mg·kg−1·d−1) 5 days per week for 2 months. We demonstrated that oral administration of rotenone to ageing mice was sufficient to establish a PD mouse model and that microglial activation and iron deposition selectively appeared in the SN of the mice prior to loss of motor coordination and dopaminergic neurons, and these events could be fully blocked by microglial elimination with a PLX5622-formulated diet. 16 S rDNA sequencing analysis showed that the gut microbiota in rotenone-treated mice was altered, and mice receiving faecal microbial transplantation (FMT) from ageing mice treated with rotenone for 2 months exhibited the same pathology in the SN. We demonstrated that C-X-C motif chemokine ligand-1 (CXCL1) was an essential molecule, as intravenous injection of CXCL1 mimicked almost all the pathology in serum and SN induced by oral rotenone and FMT. Using metabolomics and transcriptomics analyses, we identified the PPAR pathway as a key pathway involved in rotenone-induced neuronal damage. Inhibition of the PPARγ pathway was consistent in the above models, whereas its activation by linoleic acid (60 mg·kg−1·d−1, i.g. for 1 week) could block these pathological events in mice intravenously injected with CXCL1. Altogether, these results reveal that the altered gut microbiota resulted in neuroinflammation and iron deposition occurring early in the SN of ageing mice with oral administration of rotenone, much earlier than motor symptoms and dopaminergic neuron loss. We found that CXCL1 plays a crucial role in this process, possibly via PPARγ signalling inhibition. This study may pave the way for understanding the “brain-gut-microbiota” molecular regulatory networks in PD pathogenesis.

The aged C57BL/6 male mice with rotenone intragastric administration showed altered gut microbiota, which caused systemic inflammation, PPARγ signalling inhibition and neuroinflammation, brain iron deposition and ferroptosis, and eventually dopaminergic neurodegeneration in PD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Neuroinflammation and iron deposition prior to dopaminergic neurodegeneration in the SN of rotenone-induced PD mice model.
Fig. 2: Depletion of microglia by PLX5622 prevents iron deposition and nigral neurodegeneration in rotenone-induced PD mice model.
Fig. 3: Altered gut microbiota induced by rotenone contributes to microglia activation, iron deposition, and dopaminergic neuron loss in the SN of C57BL/6 mice.
Fig. 4: CXCL1 induces microglia activation, and iron deposition in the SN of C57BL/6 mice.
Fig. 5: Identification of PPARγ signalling pathway.
Fig. 6: PPARγ activation rescued microglia activation, iron deposition, and nigral dopaminergic neurodegeneration in mice with CXCL1 intravenous injection.

Similar content being viewed by others

Data availability

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

Materials availability

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

References

  1. Deng H, Wang P, Jankovic J. The genetics of Parkinson disease. Ageing Res Rev. 2018;42:72–85.

    Article  CAS  PubMed  Google Scholar 

  2. Marras C, Canning CG, Goldman SM. Environment, lifestyle, and Parkinson’s disease: implications for prevention in the next decade. Mov Disord. 2019;34:801–11.

    Article  PubMed  Google Scholar 

  3. Mattson MP, Arumugam TV. Hallmarks of brain aging: adaptive and pathological modification by metabolic states. Cell Metab. 2018;27:1176–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Challis C, Hori A, Sampson TR, Yoo BB, Challis RC, Hamilton AM, et al. Gut-seeded alpha-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice. Nat Neurosci. 2020;23:327–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Singh A, Dawson TM, Kulkarni S. Neurodegenerative disorders and gut-brain interactions. J Clin Invest. 2021;131:e143775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Willyard C. How gut microbes could drive brain disorders. Nature. 2021;590:22–5.

    Article  CAS  PubMed  Google Scholar 

  7. Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Burmann J, et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord. 2016;32:66–72.

    Article  PubMed  Google Scholar 

  8. Li W, Wu X, Hu X, Wang T, Liang S, Duan Y, et al. Structural changes of gut microbiota in Parkinson’s disease and its correlation with clinical features. Sci China Life Sci. 2017;60:1223–33.

    Article  PubMed  Google Scholar 

  9. Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell. 2016;167:1469–80.e1412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lin CH, Chen CC, Chiang HL, Liou JM, Chang CM, Lu TP, et al. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson’s disease. J Neuroinflammation. 2019;16:129.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Aho VTE, Houser MC, Pereira PAB, Chang J, Rudi K, Paulin L, et al. Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease. Mol Neurodegener. 2021;16:6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhao Z, Ning J, Bao XQ, Shang M, Ma J, Li G, et al. Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis. Microbiome. 2021;9:226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. De Filippo K, Dudeck A, Hasenberg M, Nye E, van Rooijen N, Hartmann K, et al. Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation. Blood. 2013;121:4930–7.

    Article  PubMed  Google Scholar 

  14. Farmen K, Nissen SK, Stokholm MG, Iranzo A, Ostergaard K, Serradell M, et al. Monocyte markers correlate with immune and neuronal brain changes in REM sleep behavior disorder. Proc Natl Acad Sci USA. 2021;118:e2020858118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. De Francesco E, Terzaghi M, Storelli E, Magistrelli L, Comi C, Legnaro M, et al. CD4+ T-cell transcription factors in idiopathic REM sleep behavior disorder and Parkinson’s disease. Mov Disord. 2021;36:225–9.

    Article  PubMed  Google Scholar 

  16. Zhang H, Wang T, Li Y, Mao W, Hao S, Huang Z, et al. Plasma immune markers in an idiopathic REM sleep behavior disorder cohort. Parkinsonism Relat Disord. 2020;78:145–50.

    Article  PubMed  Google Scholar 

  17. Terkelsen MH, Klaestrup IH, Hvingelby V, Lauritsen J, Pavese N, Romero-Ramos M. Neuroinflammation and immune changes in prodromal Parkinson’s disease and other synucleinopathies. J Parkinsons Dis. 2022;12:S149–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bhattarai Y, Si J, Pu M, Ross OA, McLean PJ, Till L, et al. Role of gut microbiota in regulating gastrointestinal dysfunction and motor symptoms in a mouse model of Parkinson’s disease. Gut Microbes. 2021;13:1866974.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Pan-Montojo F, Anichtchik O, Dening Y, Knels L, Pursche S, Jung R, et al. Progression of Parkinson’s disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS One. 2010;5:e8762.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Thirugnanam T, Santhakumar K. Chemically induced models of Parkinson’s disease. Comp Biochem Physiol C Toxicol Pharmacol. 2022;252:109213.

    Article  CAS  PubMed  Google Scholar 

  21. Johnson ME, Bobrovskaya L. An update on the rotenone models of Parkinson’s disease: their ability to reproduce the features of clinical disease and model gene-environment interactions. Neurotoxicology. 2015;46:101–16.

    Article  CAS  PubMed  Google Scholar 

  22. Taguchi T, Ikuno M, Yamakado H, Takahashi R. Animal model for prodromal Parkinson’s disease. Int J Mol Sci. 2020;21:1961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang N, Liu W, Zheng Y, Wang S, Yang B, Li M, et al. CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-kappaB/SOX4 signaling. Cell Death Dis. 2018;9:880.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Huang Y, Xu Z, Xiong S, Sun F, Qin G, Hu G, et al. Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion. Nat Neurosci. 2018;21:530–40.

    Article  CAS  PubMed  Google Scholar 

  25. Spangenberg E, Severson PL, Hohsfield LA, Crapser J, Zhang J, Burton EA, et al. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model. Nat Commun. 2019;10:3758.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Schuijt TJ, Lankelma JM, Scicluna BP, de Sousa e Melo F, Roelofs JJ, de Boer JD, et al. The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia. Gut. 2016;65:575–83.

    Article  CAS  PubMed  Google Scholar 

  27. Zheng X, Zhao A, Xie G, Chi Y, Zhao L, Li H, et al. Melamine-induced renal toxicity is mediated by the gut microbiota. Sci Transl Med. 2013;5:172ra122.

    Article  Google Scholar 

  28. Ali W, Ikram M, Park HY, Jo MG, Ullah R, Ahmad S, et al. Oral administration of alpha linoleic acid rescues abeta-induced glia-mediated neuroinflammation and cognitive dysfunction in C57BL/6N mice. Cells. 2020;9:667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Matias M, Silvestre S, Falcao A, Alves G. Considerations and pitfalls in selecting the drug vehicles for evaluation of new drug candidates: focus on in vivo pharmaco-toxicological assays based on the rotarod performance test. J Pharm Pharm Sci. 2018;21:110–8.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang QS, Heng Y, Mou Z, Huang JY, Yuan YH, Chen NH. Reassessment of subacute MPTP-treated mice as animal model of Parkinson’s disease. Acta Pharmacol Sin. 2017;38:1317–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang Z, Zeng YN, Yang P, Jin LQ, Xiong WC, Zhu MZ, et al. Axonal iron transport in the brain modulates anxiety-related behaviors. Nat Chem Biol. 2019;15:1214–22.

    Article  CAS  PubMed  Google Scholar 

  32. Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017;20:145–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Castellani RJ, Siedlak SL, Perry G, Smith MA. Sequestration of iron by Lewy bodies in Parkinson’s disease. Acta Neuropathol. 2000;100:111–4.

    Article  CAS  PubMed  Google Scholar 

  34. Hare DJ, Double KL. Iron and dopamine: a toxic couple. Brain. 2016;139:1026–35.

    Article  PubMed  Google Scholar 

  35. Xu YY, Wan WP, Zhao S, Ma ZG. L-type calcium channels are involved in iron-induced neurotoxicity in primary cultured ventral mesencephalon neurons of rats. Neurosci Bull. 2020;36:165–73.

    Article  PubMed  Google Scholar 

  36. Abeyawardhane DL, Lucas HR. Iron redox chemistry and implications in the Parkinson’s disease brain. Oxid Med Cell Longev. 2019;2019:4609702.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Guiney SJ, Adlard PA, Bush AI, Finkelstein DI, Ayton S. Ferroptosis and cell death mechanisms in Parkinson’s disease. Neurochem Int. 2017;104:34–48.

    Article  CAS  PubMed  Google Scholar 

  38. Sun J, Lai Z, Ma J, Gao L, Chen M, Chen J, et al. Quantitative evaluation of iron content in idiopathic rapid eye movement sleep behavior disorder. Mov Disord. 2020;35:478–85.

    Article  CAS  PubMed  Google Scholar 

  39. Rong Y, Xu Z, Zhu Y, Zhang X, Lai L, Sun S, et al. Combination of quantitative susceptibility mapping and diffusion Kurtosis imaging provides potential biomarkers for early-stage Parkinson’s disease. ACS Chem Neurosci. 2022;13:2699–708.

    Article  CAS  PubMed  Google Scholar 

  40. He N, Chen Y, LeWitt PA, Yan F, Haacke EM. Application of neuromelanin MR imaging in Parkinson disease. J Magn Reson Imaging. 2022;57:337–52.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Kim WG, Mohney RP, Wilson B, Jeohn GH, Liu B, Hong JS. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci. 2000;20:6309–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Qian ZM, Ke Y. Brain iron transport. Biol Rev Camb Philos Soc. 2019;94:1672–84.

    Article  PubMed  Google Scholar 

  43. Wang J, Song N, Jiang H, Wang J, Xie J. Pro-inflammatory cytokines modulate iron regulatory protein 1 expression and iron transportation through reactive oxygen/nitrogen species production in ventral mesencephalic neurons. Biochim Biophys Acta. 2013;1832:618–25.

    Article  CAS  PubMed  Google Scholar 

  44. McCarthy RC, Sosa JC, Gardeck AM, Baez AS, Lee CH, Wessling-Resnick M. Inflammation-induced iron transport and metabolism by brain microglia. J Biol Chem. 2018;293:7853–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Guo JJ, Yue F, Song DY, Bousset L, Liang X, Tang J, et al. Intranasal administration of alpha-synuclein preformed fibrils triggers microglial iron deposition in the substantia nigra of Macaca fascicularis. Cell Death Dis. 2021;12:81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Rathnasamy G, Ling EA, Kaur C. Consequences of iron accumulation in microglia and its implications in neuropathological conditions. CNS Neurol Disord Drug Targets. 2013;12:785–98.

    Article  CAS  PubMed  Google Scholar 

  47. Song N, Wang J, Jiang H, Xie J. Astroglial and microglial contributions to iron metabolism disturbance in Parkinson’s disease. Biochim Biophys Acta Mol Basis Dis. 2018;1864:967–73.

    Article  CAS  PubMed  Google Scholar 

  48. Caboni P, Sherer TB, Zhang N, Taylor G, Na HM, Greenamyre JT, et al. Rotenone, deguelin, their metabolites, and the rat model of Parkinson’s disease. Chem Res Toxicol. 2004;17:1540–8.

    Article  CAS  PubMed  Google Scholar 

  49. Pickard JM, Zeng MY, Caruso R, Nunez G. Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease. Immunol Rev. 2017;279:70–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Rhee SH, Pothoulakis C, Mayer EA. Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol. 2009;6:306–14.

    Article  CAS  PubMed  Google Scholar 

  51. Bairamian D, Sha S, Rolhion N, Sokol H, Dorothee G, Lemere CA, et al. Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease. Mol Neurodegener. 2022;17:19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wallen ZD, Demirkan A, Twa G, Cohen G, Dean MN, Standaert DG, et al. Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms. Nat Commun. 2022;13:6958.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Zhu X, Li B, Lou P, Dai T, Chen Y, Zhuge A, et al. The relationship between the gut microbiome and neurodegenerative diseases. Neurosci Bull. 2021;37:1510–22.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Ianiro G, Tilg H, Gasbarrini A. Antibiotics as deep modulators of gut microbiota: between good and evil. Gut. 2016;65:1906–15.

    Article  CAS  PubMed  Google Scholar 

  55. Ramirez J, Guarner F, Bustos Fernandez L, Maruy A, Sdepanian VL, Cohen H. Antibiotics as major disruptors of gut microbiota. Front Cell Infect Microbiol. 2020;10:572912.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Suez J, Zmora N, Zilberman-Schapira G, Mor U, Dori-Bachash M, Bashiardes S, et al. Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell. 2018;174:1406–23.e1416.

    Article  CAS  PubMed  Google Scholar 

  57. Hall S, Janelidze S, Surova Y, Widner H, Zetterberg H, Hansson O. Cerebrospinal fluid concentrations of inflammatory markers in Parkinson’s disease and atypical parkinsonian disorders. Sci Rep. 2018;8:13276.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Calvani R, Picca A, Landi G, Marini F, Biancolillo A, Coelho-Junior HJ, et al. A novel multi-marker discovery approach identifies new serum biomarkers for Parkinson’s disease in older people: an EXosomes in PArkiNson Disease (EXPAND) ancillary study. Geroscience. 2020;42:1323–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Huang X, Guo M, Zhang Y, Xie J, Huang R, Zuo Z, et al. Microglial IL-1RA ameliorates brain injury after ischemic stroke by inhibiting astrocytic CXCL1-mediated neutrophil recruitment and microvessel occlusion. Glia. 2023;71:1607–25.

    Article  CAS  PubMed  Google Scholar 

  60. Ransohoff RM. A polarizing question: do M1 and M2 microglia exist? Nat Neurosci. 2016;19:987–91.

    Article  CAS  PubMed  Google Scholar 

  61. Liang H, Tang T, Huang H, Li T, Gao C, Han Y, et al. Peroxisome proliferator-activated receptor-gamma ameliorates neuronal ferroptosis after traumatic brain injury in mice by inhibiting cyclooxygenase-2. Exp Neurol. 2022;354:114100.

    Article  CAS  PubMed  Google Scholar 

  62. Machado MMF, Bassani TB, Coppola-Segovia V, Moura ELR, Zanata SM, Andreatini R, et al. PPAR-gamma agonist pioglitazone reduces microglial proliferation and NF-kappaB activation in the substantia nigra in the 6-hydroxydopamine model of Parkinson’s disease. Pharmacol Rep. 2019;71:556–64.

    Article  CAS  PubMed  Google Scholar 

  63. Luo R, Su LY, Li G, Yang J, Liu Q, Yang LX, et al. Activation of PPARA-mediated autophagy reduces Alzheimer disease-like pathology and cognitive decline in a murine model. Autophagy. 2020;16:52–69.

    Article  CAS  PubMed  Google Scholar 

  64. Duan C, Jiao D, Wang H, Wu Q, Men W, Yan H, et al. Activation of the PPARgamma prevents ferroptosis-induced neuronal loss in response to intracerebral hemorrhage through synergistic actions with the Nrf2. Front Pharmacol. 2022;13:869300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Vetuschi A, Pompili S, Gaudio E, Latella G, Sferra R. PPAR-gamma with its anti-inflammatory and anti-fibrotic action could be an effective therapeutic target in IBD. Eur Rev Med Pharmacol Sci. 2018;22:8839–48.

    CAS  PubMed  Google Scholar 

  66. Luo W, Xu Q, Wang Q, Wu H, Hua J. Effect of modulation of PPAR-gamma activity on Kupffer cells M1/M2 polarization in the development of non-alcoholic fatty liver disease. Sci Rep. 2017;7:44612.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Marion-Letellier R, Savoye G, Ghosh S. Fatty acids, eicosanoids and PPAR gamma. Eur J Pharmacol. 2016;785:44–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (32170984, 31871049), the Excellent Innovative Team of Shandong Province and the Taishan Scholars Construction Project, and the Natural Science Foundation of Shandong Province (ZR2023QH110, ZR2020YQ23, and ZR2021MC116).

Author information

Authors and Affiliations

  1. Institute of Brain Science and Disease, School of Basic Medicine, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao, 266021, China

    Xi-zhen Ma, Lei-lei Chen, Le Qu, Hui Li, Jun Wang, Ning Song & Jun-xia Xie

Authors
  1. Xi-zhen Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lei-lei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Le Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ning Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jun-xia Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XZM performed experiments and composed the first draft, NS guided the experiment, polished, and finalised the article, JW and LLC guided the experiment, LQ and HL performed experiments, JXX conceived and directed the project. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Ning Song or Jun-xia Xie.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of the Medical College of Qingdao University (QDU-AEC-2022116, March 1, 2022).

Supplementary information

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

Ma, Xz., Chen, Ll., Qu, L. et al. Gut microbiota-induced CXCL1 elevation triggers early neuroinflammation in the substantia nigra of Parkinsonian mice. Acta Pharmacol Sin 45, 52–65 (2024). https://doi.org/10.1038/s41401-023-01147-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41401-023-01147-x

Keywords

Search

Advanced search

Quick links