Neuronal Prosurvival Role of Ceramide Synthase 2 by Olidogendrocyte-to-Neuron Extracellular Vesicle Transfer
Author
Other authors
Publication date
2023-03ISSN
1422-0067
Abstract
Ageing is associated with notorious alterations in neurons, i.e., in gene expression, mitochondrial function, membrane degradation or intercellular communication. However, neurons live for the entire lifespan of the individual. One of the reasons why neurons remain functional in elderly people is survival mechanisms prevail over death mechanisms. While many signals are either pro-survival or pro-death, others can play both roles. Extracellular vesicles (EVs) can signal both pro-toxicity and survival. We used young and old animals, primary neuronal and oligodendrocyte cultures and neuroblastoma and oligodendrocytic lines. We analysed our samples using a combination of proteomics and artificial neural networks, biochemistry and immunofluorescence approaches. We found an age-dependent increase in ceramide synthase 2 (CerS2) in cortical EVs, expressed by oligodendrocytes. In addition, we show that CerS2 is present in neurons via the uptake of oligodendrocyte-derived EVs. Finally, we show that age-associated inflammation and metabolic stress favour CerS2 expression and that oligodendrocyte-derived EVs loaded with CerS2 lead to the expression of the antiapoptotic factor Bcl2 in inflammatory conditions. Our study shows that intercellular communication is altered in the ageing brain, which favours neuronal survival through the transfer of oligodendrocyte-derived EVs containing CerS2.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
576 - Cellular and subcellular biology. Cytology
577 - Material bases of life. Biochemistry. Molecular biology. Biophysics
612 - Physiology. Human and comparative physiology
Keywords
Brain ageing
EVs
Exosomes
CerS2
Intercellular communication
Oligodendrocyte-to-neuron
Cervell--Envelliment
Extracellular vesicles
Interacció cel·lular
Pages
p.17
Publisher
MDPI
Is part of
International Journal of Molecular Sciences 2023, 24(6), 5986
Grant agreement number
info:eu-repo/grantAgreement/MCI/PN I+D/PID2019-104389RB-I00
info:eu-repo/grantAgreement/AEI i RyC/RYC2021-031713-I
This item appears in the following Collection(s)
Rights
© L'autor/a
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/