IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39038-8.html
   My bibliography  Save this article

The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson’s disease

Author

Listed:
  • A. de Rus Jacquet

    (Centre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences
    Université Laval
    Janelia Research Campus, Howard Hughes Medical Institute)

  • M. Alpaugh

    (Centre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences
    Université Laval
    University of Guelph)

  • H. L. Denis

    (Centre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences
    Université Laval)

  • J. L. Tancredi

    (Janelia Research Campus, Howard Hughes Medical Institute
    Cell Biology R&D, Thermo Fisher Scientific)

  • M. Boutin

    (Centre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences)

  • J. Decaestecker

    (Centre de Recherche du CHU de Québec - Université Laval, Axe Endocrinologie et Néphrologie)

  • C. Beauparlant

    (Centre de Recherche du CHU de Québec - Université Laval, Axe Endocrinologie et Néphrologie)

  • L. Herrmann

    (Centre de Recherche du CHU de Québec - Université Laval, Axe Endocrinologie et Néphrologie)

  • M. Saint-Pierre

    (Centre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences)

  • M. Parent

    (Université Laval
    CERVO Brain Research Center)

  • A. Droit

    (Centre de Recherche du CHU de Québec - Université Laval, Axe Endocrinologie et Néphrologie)

  • S. Breton

    (Centre de Recherche du CHU de Québec - Université Laval, Axe Reproduction, santé de la mère et de l’enfant
    Université Laval)

  • F. Cicchetti

    (Centre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences
    Université Laval)

Abstract

Astrocyte dysfunction has previously been linked to multiple neurodegenerative disorders including Parkinson’s disease (PD). Among their many roles, astrocytes are mediators of the brain immune response, and astrocyte reactivity is a pathological feature of PD. They are also involved in the formation and maintenance of the blood-brain barrier (BBB), but barrier integrity is compromised in people with PD. This study focuses on an unexplored area of PD pathogenesis by characterizing the interplay between astrocytes, inflammation and BBB integrity, and by combining patient-derived induced pluripotent stem cells with microfluidic technologies to generate a 3D human BBB chip. Here we report that astrocytes derived from female donors harboring the PD-related LRRK2 G2019S mutation are pro-inflammatory and fail to support the formation of a functional capillary in vitro. We show that inhibition of MEK1/2 signaling attenuates the inflammatory profile of mutant astrocytes and rescues BBB formation, providing insights into mechanisms regulating barrier integrity in PD. Lastly, we confirm that vascular changes are also observed in the human postmortem substantia nigra of both males and females with PD.

Suggested Citation

  • A. de Rus Jacquet & M. Alpaugh & H. L. Denis & J. L. Tancredi & M. Boutin & J. Decaestecker & C. Beauparlant & L. Herrmann & M. Saint-Pierre & M. Parent & A. Droit & S. Breton & F. Cicchetti, 2023. "The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson’s disease," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39038-8
    DOI: 10.1038/s41467-023-39038-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39038-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39038-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Vasiliki Panagiotakopoulou & Dina Ivanyuk & Silvia De Cicco & Wadood Haq & Aleksandra Arsić & Cong Yu & Daria Messelodi & Marvin Oldrati & David C. Schöndorf & Maria-Jose Perez & Ruggiero Pio Cassatel, 2020. "Interferon-γ signaling synergizes with LRRK2 in neurons and microglia derived from human induced pluripotent stem cells," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    2. Insup Choi & Beomsue Kim & Ji-Won Byun & Sung Hoon Baik & Yun Hyun Huh & Jong-Hyeon Kim & Inhee Mook-Jung & Woo Keun Song & Joo-Ho Shin & Hyemyung Seo & Young Ho Suh & Ilo Jou & Sang Myun Park & Ho Ch, 2015. "LRRK2 G2019S mutation attenuates microglial motility by inhibiting focal adhesion kinase," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    3. Shane A. Liddelow & Kevin A. Guttenplan & Laura E. Clarke & Frederick C. Bennett & Christopher J. Bohlen & Lucas Schirmer & Mariko L. Bennett & Alexandra E. Münch & Won-Suk Chung & Todd C. Peterson & , 2017. "Neurotoxic reactive astrocytes are induced by activated microglia," Nature, Nature, vol. 541(7638), pages 481-487, January.
    4. Sonja Kriks & Jae-Won Shim & Jinghua Piao & Yosif M. Ganat & Dustin R. Wakeman & Zhong Xie & Luis Carrillo-Reid & Gordon Auyeung & Chris Antonacci & Amanda Buch & Lichuan Yang & M. Flint Beal & D. Jam, 2011. "Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease," Nature, Nature, vol. 480(7378), pages 547-551, December.
    5. Lê, Sébastien & Josse, Julie & Husson, François, 2008. "FactoMineR: An R Package for Multivariate Analysis," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 25(i01).
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Surun, Clément & Drechsler, Martin, 2018. "Effectiveness of Tradable Permits for the Conservation of Metacommunities With Two Competing Species," Ecological Economics, Elsevier, vol. 147(C), pages 189-196.
    2. Alexander Platzer & Thomas Nussbaumer & Thomas Karonitsch & Josef S Smolen & Daniel Aletaha, 2019. "Analysis of gene expression in rheumatoid arthritis and related conditions offers insights into sex-bias, gene biotypes and co-expression patterns," PLOS ONE, Public Library of Science, vol. 14(7), pages 1-23, July.
    3. Baccar, Mariem & Raynal, Hélène & Sekhar, Muddu & Bergez, Jacques-Eric & Willaume, Magali & Casel, Pierre & Giriraj, P. & Murthy, Sanjeeva & Ruiz, Laurent, 2023. "Dynamics of crop category choices reveal strategies and tactics used by smallholder farmers in India to cope with unreliable water availability," Agricultural Systems, Elsevier, vol. 211(C).
    4. Aditi Sahu & Kivanc Kose & Lukas Kraehenbuehl & Candice Byers & Aliya Holland & Teguru Tembo & Anthony Santella & Anabel Alfonso & Madison Li & Miguel Cordova & Melissa Gill & Christi Fox & Salvador G, 2022. "In vivo tumor immune microenvironment phenotypes correlate with inflammation and vasculature to predict immunotherapy response," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    5. Roopam Shukla & Ankit Agarwal & Kamna Sachdeva & Juergen Kurths & P. K. Joshi, 2019. "Climate change perception: an analysis of climate change and risk perceptions among farmer types of Indian Western Himalayas," Climatic Change, Springer, vol. 152(1), pages 103-119, January.
    6. Cholez, Celia & Pauly, Olivier & Mahdad, Maral & Mehrabi, Sepide & Giagnocavo, Cynthia & Bijman, Jos, 2023. "Heterogeneity of inter-organizational collaborations in agrifood chain sustainability-oriented innovations," Agricultural Systems, Elsevier, vol. 212(C).
    7. Munten, Pauline & Swaen, Valérie & Vanhamme, Joëlle, 2024. "Exploring rebound effects in Access-Based services (ABS)," Journal of Business Research, Elsevier, vol. 182(C).
    8. Faith H. Brennan & Yang Li & Cankun Wang & Anjun Ma & Qi Guo & Yi Li & Nicole Pukos & Warren A. Campbell & Kristina G. Witcher & Zhen Guan & Kristina A. Kigerl & Jodie C. E. Hall & Jonathan P. Godbout, 2022. "Microglia coordinate cellular interactions during spinal cord repair in mice," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    9. Florence Jacquet & A Aboul-Naga & Bernard Hubert, 2020. "The contribution of ARIMNet to address livestock systems resilience in the Mediterranean region," Post-Print hal-03625860, HAL.
    10. Marika Vitali & Paolo Bosi & Elena Santacroce & Paolo Trevisi, 2021. "The multivariate approach identifies relationships between pre-slaughter factors, body lesions, ham defects and carcass traits in pigs," PLOS ONE, Public Library of Science, vol. 16(5), pages 1-14, May.
    11. Silvana Nisgoski & Joielan Xipaia dos Santos & Helena Cristina Vieira & Tawani Lorena Naide & Rafaela Stange & Washington Duarte Silva da Silva & Deivison Venicio Souza & Natally Celestino Gama & Márc, 2023. "Provenance Identification of Leaves and Nuts of Bertholletia excelsa Bonpl by Near-Infrared Spectroscopy and Color Parameters for Sustainable Extraction," Sustainability, MDPI, vol. 15(21), pages 1-15, November.
    12. Miranda D Stobbe & Gian A Thun & Andrea Diéguez-Docampo & Meritxell Oliva & Justin P Whalley & Emanuele Raineri & Ivo G Gut, 2019. "Recurrent somatic mutations reveal new insights into consequences of mutagenic processes in cancer," PLOS Computational Biology, Public Library of Science, vol. 15(11), pages 1-27, November.
    13. Alessandro Bonadonna & Stefano Duglio & Luigi Bollani & Giovanni Peira, 2022. "Mountain Food Products: A Cluster Analysis Based on Young Consumers’ Perceptions," Sustainability, MDPI, vol. 14(19), pages 1-14, September.
    14. Cyrille Bassolo Baki & Joost Wellens & Farid Traoré & Sié Palé & Bakary Djaby & Apolline Bambara & Nguyen T. T. Thao & Missa Hié & Bernard Tychon, 2022. "Assessment of Hydro-Agricultural Infrastructures in Burkina Faso by Using Multiple Correspondence Analysis Approach," Sustainability, MDPI, vol. 14(20), pages 1-20, October.
    15. Gennifer Meldrum & Dunja Mijatović & Wilfredo Rojas & Juana Flores & Milton Pinto & Grover Mamani & Eleuterio Condori & David Hilaquita & Helga Gruberg & Stefano Padulosi, 2018. "Climate change and crop diversity: farmers’ perceptions and adaptation on the Bolivian Altiplano," Environment, Development and Sustainability: A Multidisciplinary Approach to the Theory and Practice of Sustainable Development, Springer, vol. 20(2), pages 703-730, April.
    16. Claire H Luby & Julie C Dawson & Irwin L Goldman, 2016. "Assessment and Accessibility of Phenotypic and Genotypic Diversity of Carrot (Daucus carota L. var. sativus) Cultivars Commercially Available in the United States," PLOS ONE, Public Library of Science, vol. 11(12), pages 1-19, December.
    17. Hugo R Oliveira & Diana Tomás & Manuela Silva & Susana Lopes & Wanda Viegas & Maria Manuela Veloso, 2016. "Genetic Diversity and Population Structure in Vicia faba L. Landraces and Wild Related Species Assessed by Nuclear SSRs," PLOS ONE, Public Library of Science, vol. 11(5), pages 1-18, May.
    18. Bottaro, Giorgia & Liagre, Ludwig & Pettenella, Davide, 2024. "The Forest Sector in EU Member States' National Recovery and Resilience Plans: a preliminary analysis," Forest Policy and Economics, Elsevier, vol. 160(C).
    19. Julio E Peironcely & Theo Reijmers & Leon Coulier & Andreas Bender & Thomas Hankemeier, 2011. "Understanding and Classifying Metabolite Space and Metabolite-Likeness," PLOS ONE, Public Library of Science, vol. 6(12), pages 1-14, December.
    20. Hyun-Sik Yang & Ling Teng & Daniel Kang & Vilas Menon & Tian Ge & Hilary K. Finucane & Aaron P. Schultz & Michael Properzi & Hans-Ulrich Klein & Lori B. Chibnik & Julie A. Schneider & David A. Bennett, 2023. "Cell-type-specific Alzheimer’s disease polygenic risk scores are associated with distinct disease processes in Alzheimer’s disease," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39038-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.