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Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons

Recent studies have demonstrated that human tau can be secreted by neurons and non-neuronal cells, an event linked to the propagation of tau pathology in the brain. In the present study, we confirmed that under physiological conditions, one tau-positive band was detected in the culture medium with a...

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Autores principales: Mohamed, Nguyen-Vi, Plouffe, Vanessa, Rémillard-Labrosse, Gaudeline, Planel, Emmanuel, Leclerc, Nicole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101526/
https://www.ncbi.nlm.nih.gov/pubmed/25030297
http://dx.doi.org/10.1038/srep05715
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author Mohamed, Nguyen-Vi
Plouffe, Vanessa
Rémillard-Labrosse, Gaudeline
Planel, Emmanuel
Leclerc, Nicole
author_facet Mohamed, Nguyen-Vi
Plouffe, Vanessa
Rémillard-Labrosse, Gaudeline
Planel, Emmanuel
Leclerc, Nicole
author_sort Mohamed, Nguyen-Vi
collection PubMed
description Recent studies have demonstrated that human tau can be secreted by neurons and non-neuronal cells, an event linked to the propagation of tau pathology in the brain. In the present study, we confirmed that under physiological conditions, one tau-positive band was detected in the culture medium with an anti-tau antibody recognizing total tau and the Tau-1 antibody directed against unphosphorylated tau. We then examined whether tau secretion was modified upon insults. Tau secretion was increased by starvation [Earle's Balanced Salt Solution (EBSS)], inhibition of lysosomal function (leupeptin) and when both of these conditions were superimposed, this combined treatment having the most important effects on tau secretion. Interestingly, the pattern of tau secretion was distinct from that of control neurons when neurons were treated either with EBSS alone or EBSS + leupeptin. In these conditions, three tau-positive bands were detected in the culture medium. Two of these three bands were immunoreactive to Tau-1 antibody revealing that at least two tau species were released upon these treatments. Collectively, our results indicate that insults such as nutrient deprivation and lysosomal dysfunction observed in neurodegenerative diseases could result in an increase of tau secretion and propagation of tau pathology in the brain.
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spelling pubmed-41015262014-07-17 Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons Mohamed, Nguyen-Vi Plouffe, Vanessa Rémillard-Labrosse, Gaudeline Planel, Emmanuel Leclerc, Nicole Sci Rep Article Recent studies have demonstrated that human tau can be secreted by neurons and non-neuronal cells, an event linked to the propagation of tau pathology in the brain. In the present study, we confirmed that under physiological conditions, one tau-positive band was detected in the culture medium with an anti-tau antibody recognizing total tau and the Tau-1 antibody directed against unphosphorylated tau. We then examined whether tau secretion was modified upon insults. Tau secretion was increased by starvation [Earle's Balanced Salt Solution (EBSS)], inhibition of lysosomal function (leupeptin) and when both of these conditions were superimposed, this combined treatment having the most important effects on tau secretion. Interestingly, the pattern of tau secretion was distinct from that of control neurons when neurons were treated either with EBSS alone or EBSS + leupeptin. In these conditions, three tau-positive bands were detected in the culture medium. Two of these three bands were immunoreactive to Tau-1 antibody revealing that at least two tau species were released upon these treatments. Collectively, our results indicate that insults such as nutrient deprivation and lysosomal dysfunction observed in neurodegenerative diseases could result in an increase of tau secretion and propagation of tau pathology in the brain. Nature Publishing Group 2014-07-17 /pmc/articles/PMC4101526/ /pubmed/25030297 http://dx.doi.org/10.1038/srep05715 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Article
Mohamed, Nguyen-Vi
Plouffe, Vanessa
Rémillard-Labrosse, Gaudeline
Planel, Emmanuel
Leclerc, Nicole
Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons
title Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons
title_full Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons
title_fullStr Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons
title_full_unstemmed Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons
title_short Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons
title_sort starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101526/
https://www.ncbi.nlm.nih.gov/pubmed/25030297
http://dx.doi.org/10.1038/srep05715
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