Neural stem cell‐derived exosomes revert HFD-dependent memory impairment via CREB‐BDNF signalling
Articolo
Data di Pubblicazione:
2020
Citazione:
Spinelli, M., Natale, F., Rinaudo, M., Leone, L., Mezzogori, D., Fusco, S., Grassi, C., Neural stem cell‐derived exosomes revert HFD-dependent memory impairment via CREB‐BDNF signalling, <>, 2020; 2020 (21): N/A-N/A. [doi:10.3390/ijms21238994] [http://hdl.handle.net/10807/164173]
Abstract:
Overnutrition and metabolic disorders impair cognitive functions through molecular
mechanisms still poorly understood. In mice fed with a high fat diet (HFD) we analysed the
expression of synaptic plasticity‐related genes and the activation of cAMP response elementbinding
protein (CREB)‐brain‐derived neurotrophic factor (BDNF)‐tropomyosin receptor kinase B
(TrkB) signalling. We found that a HFD inhibited both CREB phosphorylation and the expression
of a set of CREB target genes in the hippocampus. The intranasal administration of neural stem cell
(NSC)‐derived exosomes (exo‐NSC) epigenetically restored the transcription of Bdnf, nNOS, Sirt1,
Egr3, and RelA genes by inducing the recruitment of CREB on their regulatory sequences. Finally,
exo‐NSC administration rescued both BDNF signalling and memory in HFD mice. Collectively, our
findings highlight novel mechanisms underlying HFD‐related memory impairment and provide
evidence of the potential therapeutic effect of exo‐NSC against metabolic disease‐related cognitive
decline
mechanisms still poorly understood. In mice fed with a high fat diet (HFD) we analysed the
expression of synaptic plasticity‐related genes and the activation of cAMP response elementbinding
protein (CREB)‐brain‐derived neurotrophic factor (BDNF)‐tropomyosin receptor kinase B
(TrkB) signalling. We found that a HFD inhibited both CREB phosphorylation and the expression
of a set of CREB target genes in the hippocampus. The intranasal administration of neural stem cell
(NSC)‐derived exosomes (exo‐NSC) epigenetically restored the transcription of Bdnf, nNOS, Sirt1,
Egr3, and RelA genes by inducing the recruitment of CREB on their regulatory sequences. Finally,
exo‐NSC administration rescued both BDNF signalling and memory in HFD mice. Collectively, our
findings highlight novel mechanisms underlying HFD‐related memory impairment and provide
evidence of the potential therapeutic effect of exo‐NSC against metabolic disease‐related cognitive
decline
Tipologia CRIS:
Articolo in rivista, Nota a sentenza
Keywords:
CREB; synaptic plasticity; high fat diet; exosomes; memory deficits; BDNF; personalized medicine; epigenetics
Elenco autori:
Spinelli, Matteo; Natale, Francesca; Rinaudo, Marco; Leone, Lucia; Mezzogori, D; Fusco, Salvatore; Grassi, Claudio
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