IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v627y2024i8004d10.1038_s41586-024-07109-5.html
   My bibliography  Save this article

A concerted neuron–astrocyte program declines in ageing and schizophrenia

Author

Listed:
  • Emi Ling

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • James Nemesh

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Melissa Goldman

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Nolan Kamitaki

    (Broad Institute of MIT and Harvard
    Harvard Medical School
    Harvard Medical School)

  • Nora Reed

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Robert E. Handsaker

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Giulio Genovese

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Jonathan S. Vogelgsang

    (McLean Hospital
    Harvard Medical School)

  • Sherif Gerges

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Seva Kashin

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Sulagna Ghosh

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • John M. Esposito

    (McLean Hospital)

  • Kiely Morris

    (McLean Hospital)

  • Daniel Meyer

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Alyssa Lutservitz

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Christopher D. Mullally

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Alec Wysoker

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Liv Spina

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Anna Neumann

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Marina Hogan

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Kiku Ichihara

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Sabina Berretta

    (Broad Institute of MIT and Harvard
    McLean Hospital
    Harvard Medical School
    Harvard Medical School)

  • Steven A. McCarroll

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

Abstract

Human brains vary across people and over time; such variation is not yet understood in cellular terms. Here we describe a relationship between people’s cortical neurons and cortical astrocytes. We used single-nucleus RNA sequencing to analyse the prefrontal cortex of 191 human donors aged 22–97 years, including healthy individuals and people with schizophrenia. Latent-factor analysis of these data revealed that, in people whose cortical neurons more strongly expressed genes encoding synaptic components, cortical astrocytes more strongly expressed distinct genes with synaptic functions and genes for synthesizing cholesterol, an astrocyte-supplied component of synaptic membranes. We call this relationship the synaptic neuron and astrocyte program (SNAP). In schizophrenia and ageing—two conditions that involve declines in cognitive flexibility and plasticity1,2—cells divested from SNAP: astrocytes, glutamatergic (excitatory) neurons and GABAergic (inhibitory) neurons all showed reduced SNAP expression to corresponding degrees. The distinct astrocytic and neuronal components of SNAP both involved genes in which genetic risk factors for schizophrenia were strongly concentrated. SNAP, which varies quantitatively even among healthy people of similar age, may underlie many aspects of normal human interindividual differences and may be an important point of convergence for multiple kinds of pathophysiology.

Suggested Citation

  • Emi Ling & James Nemesh & Melissa Goldman & Nolan Kamitaki & Nora Reed & Robert E. Handsaker & Giulio Genovese & Jonathan S. Vogelgsang & Sherif Gerges & Seva Kashin & Sulagna Ghosh & John M. Esposito, 2024. "A concerted neuron–astrocyte program declines in ageing and schizophrenia," Nature, Nature, vol. 627(8004), pages 604-611, March.
    • Handle: RePEc:nat:nature:v:627:y:2024:i:8004:d:10.1038_s41586-024-07109-5
    DOI: 10.1038/s41586-024-07109-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-024-07109-5
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-024-07109-5?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    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:nature:v:627:y:2024:i:8004:d:10.1038_s41586-024-07109-5. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.