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.

Maternal insulin resistance multigenerationally impairs synaptic plasticity and memory via gametic mechanisms / Fusco, S; Spinelli, M; Cocco, S; Ripoli, C; Mastrodonato, A; Natale, F; Rinaudo, M; Livrizzi, G; Grassi, C. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 10:(2019). [10.1038/s41467-019-12793-3]

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

Spinelli M;
2019-01-01

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.
2019
Maternal insulin resistance multigenerationally impairs synaptic plasticity and memory via gametic mechanisms / Fusco, S; Spinelli, M; Cocco, S; Ripoli, C; Mastrodonato, A; Natale, F; Rinaudo, M; Livrizzi, G; Grassi, C. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 10:(2019). [10.1038/s41467-019-12793-3]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/327952
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