Neural stem cell‐derived exosomes revert hfd‐ dependent memory impairment via creb‐bdnf signalling

Matteo Spinelli, Francesca Natale, Marco Rinaudo, Lucia Leone, Daniele Mezzogori, Salvatore Fusco, Claudio Grassi

Research output: Contribution to journalArticlepeer-review

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 element-binding 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.

Original languageEnglish
Article number8994
Pages (from-to)1-16
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume21
Issue number23
DOIs
Publication statusPublished - Dec 1 2020

Keywords

  • BDNF
  • CREB
  • Epigenetics
  • Exosomes
  • High fat diet
  • Memory deficits
  • Personalized medicine
  • Synaptic plasticity

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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