Neural Stem Cell-Derived Exosomes Revert HFD-Dependent Memory Impairment via CREB-BDNF Signalling.
Animals
Brain-Derived Neurotrophic Factor
/ metabolism
Cyclic AMP Response Element-Binding Protein
/ metabolism
Diet, High-Fat
Down-Regulation
/ genetics
Exosomes
/ metabolism
Hippocampus
/ metabolism
Male
Memory Disorders
/ genetics
Mice, Inbred C57BL
Neural Stem Cells
/ metabolism
Neuronal Plasticity
/ genetics
Receptor, trkB
/ metabolism
Signal Transduction
Transcription, Genetic
BDNF
CREB
epigenetics
exosomes
high fat diet
memory deficits
personalized medicine
synaptic plasticity
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
26 Nov 2020
26 Nov 2020
Historique:
received:
06
10
2020
revised:
20
11
2020
accepted:
25
11
2020
entrez:
1
12
2020
pubmed:
2
12
2020
medline:
5
3
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33256199
pii: ijms21238994
doi: 10.3390/ijms21238994
pmc: PMC7729830
pii:
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
Cyclic AMP Response Element-Binding Protein
0
Receptor, trkB
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Italian Ministry of Health
ID : GR-2018-12366381
Organisme : Università Cattolica del Sacro Cuore
ID : Linea D.3.2 2017
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