IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-12793-3.html
   My bibliography  Save this article

Maternal insulin resistance multigenerationally impairs synaptic plasticity and memory via gametic mechanisms

Author

Listed:
  • Salvatore Fusco

    (Fondazione Policlinico Universitario A. Gemelli IRCCS
    Institute of Human Physiology, Università Cattolica del Sacro Cuore)

  • Matteo Spinelli

    (Institute of Human Physiology, Università Cattolica del Sacro Cuore)

  • Sara Cocco

    (Institute of Human Physiology, Università Cattolica del Sacro Cuore)

  • Cristian Ripoli

    (Fondazione Policlinico Universitario A. Gemelli IRCCS
    Institute of Human Physiology, Università Cattolica del Sacro Cuore)

  • Alessia Mastrodonato

    (Institute of Human Physiology, Università Cattolica del Sacro Cuore)

  • Francesca Natale

    (Institute of Human Physiology, Università Cattolica del Sacro Cuore)

  • Marco Rinaudo

    (Institute of Human Physiology, Università Cattolica del Sacro Cuore)

  • Giulia Livrizzi

    (Institute of Human Physiology, Università Cattolica del Sacro Cuore)

  • Claudio Grassi

    (Fondazione Policlinico Universitario A. Gemelli IRCCS
    Institute of Human Physiology, Università Cattolica del Sacro Cuore)

Abstract

Metabolic diseases harm brain health and cognitive functions, but whether maternal metabolic unbalance may affect brain plasticity of next generations is still unclear. Here, we demonstrate that maternal high fat diet (HFD)-dependent insulin resistance multigenerationally impairs synaptic plasticity, learning and memory. HFD downregulates BDNF and insulin signaling in maternal tissues and epigenetically inhibits BDNF expression in both germline and hippocampus of progeny. Notably, exposure of the HFD offspring to novel enriched environment restores Bdnf epigenetic activation in the male germline and counteracts the transmission of cognitive impairment to the next generations. BDNF administration to HFD-fed mothers or preserved insulin sensitivity in HFD-fed p66Shc KO mice also prevents the intergenerational transmission of brain damage to the progeny. Collectively, our data suggest that maternal diet multigenerationally impacts on descendants’ brain health via gametic mechanisms susceptible to lifestyle.

Suggested Citation

  • Salvatore Fusco & Matteo Spinelli & Sara Cocco & Cristian Ripoli & Alessia Mastrodonato & Francesca Natale & Marco Rinaudo & Giulia Livrizzi & Claudio Grassi, 2019. "Maternal insulin resistance multigenerationally impairs synaptic plasticity and memory via gametic mechanisms," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12793-3
    DOI: 10.1038/s41467-019-12793-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-12793-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-12793-3?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
    ---><---

    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:10:y:2019:i:1:d:10.1038_s41467-019-12793-3. 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.