IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29506-y.html
   My bibliography  Save this article

Stearoyl-CoA Desaturase inhibition reverses immune, synaptic and cognitive impairments in an Alzheimer’s disease mouse model

Author

Listed:
  • Laura K. Hamilton

    (Université de Montréal
    Université de Montréal)

  • Gaël Moquin-Beaudry

    (Université de Montréal
    Université de Montréal)

  • Chenicka L. Mangahas

    (Université de Montréal
    Université de Montréal)

  • Federico Pratesi

    (Université de Montréal
    Université de Montréal
    CIUSSS de l’Estrie-CHUS
    Université de Sherbrooke)

  • Myriam Aubin

    (CIUSSS de l’Estrie-CHUS
    Université de Sherbrooke)

  • Anne Aumont

    (Université de Montréal
    Université de Montréal
    CIUSSS de l’Estrie-CHUS
    Université de Sherbrooke)

  • Sandra E. Joppé

    (Université de Montréal
    Université de Montréal)

  • Alexandre Légiot

    (Université de Québec à Montréal (UQAM))

  • Annick Vachon

    (CIUSSS de l’Estrie-CHUS
    Université de Sherbrooke)

  • Mélanie Plourde

    (CIUSSS de l’Estrie-CHUS
    Université de Sherbrooke)

  • Catherine Mounier

    (Université de Québec à Montréal (UQAM))

  • Martine Tétreault

    (Université de Montréal
    Université de Montréal)

  • Karl J. L. Fernandes

    (Université de Montréal
    Université de Montréal
    CIUSSS de l’Estrie-CHUS
    Université de Sherbrooke)

Abstract

The defining features of Alzheimer’s disease (AD) include alterations in protein aggregation, immunity, lipid metabolism, synapses, and learning and memory. Of these, lipid abnormalities are the least understood. Here, we investigate the role of Stearoyl-CoA desaturase (SCD), a crucial regulator of fatty acid desaturation, in AD pathogenesis. We show that inhibiting brain SCD activity for 1-month in the 3xTg mouse model of AD alters core AD-related transcriptomic pathways in the hippocampus, and that it concomitantly restores essential components of hippocampal function, including dendritic spines and structure, immediate-early gene expression, and learning and memory itself. Moreover, SCD inhibition dampens activation of microglia, key mediators of spine loss during AD and the main immune cells of the brain. These data reveal that brain fatty acid metabolism links AD genes to downstream immune, synaptic, and functional impairments, identifying SCD as a potential target for AD treatment.

Suggested Citation

  • Laura K. Hamilton & Gaël Moquin-Beaudry & Chenicka L. Mangahas & Federico Pratesi & Myriam Aubin & Anne Aumont & Sandra E. Joppé & Alexandre Légiot & Annick Vachon & Mélanie Plourde & Catherine Mounie, 2022. "Stearoyl-CoA Desaturase inhibition reverses immune, synaptic and cognitive impairments in an Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29506-y
    DOI: 10.1038/s41467-022-29506-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29506-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29506-y?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. Chenwei Li & Baolin Liu & Boxi Kang & Zedao Liu & Yedan Liu & Changya Chen & Xianwen Ren & Zemin Zhang, 2020. "SciBet as a portable and fast single cell type identifier," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    2. Kevin Huynh & Wei Ling Florence Lim & Corey Giles & Kaushala S. Jayawardana & Agus Salim & Natalie A. Mellett & Adam Alexander T. Smith & Gavriel Olshansky & Brian G. Drew & Pratishtha Chatterjee & Ia, 2020. "Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    3. Elizabeth Spangenberg & Paul L. Severson & Lindsay A. Hohsfield & Joshua Crapser & Jiazhong Zhang & Elizabeth A. Burton & Ying Zhang & Wayne Spevak & Jack Lin & Nicole Y. Phan & Gaston Habets & Andrey, 2019. "Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model," Nature Communications, Nature, vol. 10(1), pages 1-21, December.
    4. Paras S. Minhas & Amira Latif-Hernandez & Melanie R. McReynolds & Aarooran S. Durairaj & Qian Wang & Amanda Rubin & Amit U. Joshi & Joy Q. He & Esha Gauba & Ling Liu & Congcong Wang & Miles Linde & Yu, 2021. "Restoring metabolism of myeloid cells reverses cognitive decline in ageing," Nature, Nature, vol. 590(7844), pages 122-128, February.
    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. Yannick Fotio & Alex Mabou Tagne & Erica Squire & Hye-lim Lee & Connor M. Phillips & Kayla Chang & Faizy Ahmed & Andrew S. Greenberg & S. Armando Villalta & Vanessa M. Scarfone & Gilberto Spadoni & Ma, 2024. "NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Augusto Faria Andrade & Alva Annett & Elham Karimi & Danai Georgia Topouza & Morteza Rezanejad & Yitong Liu & Michael McNicholas & Eduardo G. Gonzalez Santiago & Dhana Llivichuzhca-Loja & Arne Gehlhaa, 2024. "Immune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting function," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Noah R. Johnson & Peng Yuan & Erika Castillo & T. Peter Lopez & Weizhou Yue & Annalise Bond & Brianna M. Rivera & Miranda C. Sullivan & Masakazu Hirouchi & Kurt Giles & Atsushi Aoyagi & Carlo Condello, 2023. "CSF1R inhibitors induce a sex-specific resilient microglial phenotype and functional rescue in a tauopathy mouse model," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    4. Gemma Cadby & Corey Giles & Phillip E. Melton & Kevin Huynh & Natalie A. Mellett & Thy Duong & Anh Nguyen & Michelle Cinel & Alex Smith & Gavriel Olshansky & Tingting Wang & Marta Brozynska & Mike Ino, 2022. "Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Judy Chen & Jane C. Deng & Rachel L. Zemans & Karim Bahmed & Beata Kosmider & Min Zhang & Marc Peters-Golden & Daniel R. Goldstein, 2022. "Age-induced prostaglandin E2 impairs mitochondrial fitness and increases mortality to influenza infection," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Rongbo Shen & Lin Liu & Zihan Wu & Ying Zhang & Zhiyuan Yuan & Junfu Guo & Fan Yang & Chao Zhang & Bichao Chen & Wanwan Feng & Chao Liu & Jing Guo & Guozhen Fan & Yong Zhang & Yuxiang Li & Xun Xu & Ji, 2022. "Spatial-ID: a cell typing method for spatially resolved transcriptomics via transfer learning and spatial embedding," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Niranjana Natarajan & Jonathan Florentin & Ebin Johny & Hanxi Xiao & Scott Patrick O’Neil & Liqun Lei & Jixing Shen & Lee Ohayon & Aaron R. Johnson & Krithika Rao & Xiaoyun Li & Yanwu Zhao & Yingze Zh, 2024. "Aberrant mitochondrial DNA synthesis in macrophages exacerbates inflammation and atherosclerosis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    8. Rasmus Berglund & Yufei Cheng & Eliane Piket & Milena Z. Adzemovic & Manuel Zeitelhofer & Tomas Olsson & Andre Ortlieb Guerreiro-Cacais & Maja Jagodic, 2024. "The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    9. Stefano Suzzi & Tommaso Croese & Adi Ravid & Or Gold & Abbe R. Clark & Sedi Medina & Daniel Kitsberg & Miriam Adam & Katherine A. Vernon & Eva Kohnert & Inbar Shapira & Sergey Malitsky & Maxim Itkin &, 2023. "N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    10. Oana A. Zeleznik & Jae H. Kang & Jessica Lasky-Su & A. Heather Eliassen & Lisa Frueh & Clary B. Clish & Bernard A. Rosner & Tobias Elze & Pirro Hysi & Anthony Khawaja & Janey L. Wiggs & Louis R. Pasqu, 2023. "Plasma metabolite profile for primary open-angle glaucoma in three US cohorts and the UK Biobank," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    11. Alicia Bedolla & Elliot Wegman & Max Weed & Messiyah K. Stevens & Kierra Ware & Aditi Paranjpe & Anastasia Alkhimovitch & Igal Ifergan & Aleksandr Taranov & Joshua D. Peter & Rosa Maria Salazar Gonzal, 2024. "Adult microglial TGFβ1 is required for microglia homeostasis via an autocrine mechanism to maintain cognitive function in mice," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    12. Anaísa V. Ferreira & Juan Carlos Alarcon-Barrera & Jorge Domínguez-Andrés & Özlem Bulut & Gizem Kilic & Priya A. Debisarun & Rutger J. Röring & Hatice N. Özhan & Eva Terschlüsen & Athanasios Ziogas & , 2023. "Fatty acid desaturation and lipoxygenase pathways support trained immunity," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    13. Jiawei Chen & Hao Xu & Wanyu Tao & Zhaoxiong Chen & Yuxuan Zhao & Jing-Dong J. Han, 2023. "Transformer for one stop interpretable cell type annotation," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    14. Xin Li & Bairu Li & Shaobin Gu & Xinyue Pang & Patrick Mason & Jiangfeng Yuan & Jingyu Jia & Jiaju Sun & Chunyan Zhao & Robert Henry, 2024. "Single-cell and spatial RNA sequencing reveal the spatiotemporal trajectories of fruit senescence," Nature Communications, Nature, vol. 15(1), pages 1-19, 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:13:y:2022:i:1:d:10.1038_s41467-022-29506-y. 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.