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

Salvatore Fusco, Matteo Spinelli, Sara Cocco, Cristian Ripoli, Alessia Mastrodonato, Francesca Natale, Marco Rinaudo, Giulia Livrizzi, Claudio Grassi

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

14 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
Numero di pagine17
RivistaNature Communications
Volume10
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • Metabolic diseases
  • brain plasticity
  • insulin resistance

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