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Dysregulated Neurotransmission induces Trans-synaptic degeneration in reconstructed Neuronal Networks

Increasing evidence suggests that pathological hallmarks of chronic degenerative syndromes progressively spread among interconnected brain areas in a disease-specific stereotyped pattern. Functional brain imaging from patients affected by various neurological syndromes such as traumatic brain injury...

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Autores principales: Deleglise, Bérangère, Lassus, Benjamin, Soubeyre, Vanessa, Doulazmi, Mohamed, Brugg, Bernard, Vanhoutte, Peter, Peyrin, Jean-Michel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072786/
https://www.ncbi.nlm.nih.gov/pubmed/30072750
http://dx.doi.org/10.1038/s41598-018-29918-1
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author Deleglise, Bérangère
Lassus, Benjamin
Soubeyre, Vanessa
Doulazmi, Mohamed
Brugg, Bernard
Vanhoutte, Peter
Peyrin, Jean-Michel
author_facet Deleglise, Bérangère
Lassus, Benjamin
Soubeyre, Vanessa
Doulazmi, Mohamed
Brugg, Bernard
Vanhoutte, Peter
Peyrin, Jean-Michel
author_sort Deleglise, Bérangère
collection PubMed
description Increasing evidence suggests that pathological hallmarks of chronic degenerative syndromes progressively spread among interconnected brain areas in a disease-specific stereotyped pattern. Functional brain imaging from patients affected by various neurological syndromes such as traumatic brain injury and stroke indicates that the progression of such diseases follows functional connections, rather than simply spreading to structurally adjacent areas. Indeed, initial damage to a given brain area was shown to disrupt the communication in related brain networks. Using cortico-striatal neuronal networks reconstructed in a microfluidic environment, we investigated the role of glutamate signaling in activity-dependent neuronal survival and trans-synaptic degeneration processes. Using a variety of neuronal insults applied on cortical neurons, we demonstrate that acute injuries such as axonal trauma, focal ischemia, or alteration of neuronal rhythms, lead to glutamate-dependent striatal neuron dysfunction. Interestingly, focal pro-oxidant insults or chronic alteration of spontaneous cortical rhythms provoked dysfunction of distant striatal neurons through abnormal glutamate GluN2B-NMDAR-mediated signaling at cortico-striatal synapses. These results indicate that focal alteration of cortical functions can initiate spreading of dysfunction along neuronal pathways in the brain, reminiscent of diaschisis-like processes.
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spelling pubmed-60727862018-08-07 Dysregulated Neurotransmission induces Trans-synaptic degeneration in reconstructed Neuronal Networks Deleglise, Bérangère Lassus, Benjamin Soubeyre, Vanessa Doulazmi, Mohamed Brugg, Bernard Vanhoutte, Peter Peyrin, Jean-Michel Sci Rep Article Increasing evidence suggests that pathological hallmarks of chronic degenerative syndromes progressively spread among interconnected brain areas in a disease-specific stereotyped pattern. Functional brain imaging from patients affected by various neurological syndromes such as traumatic brain injury and stroke indicates that the progression of such diseases follows functional connections, rather than simply spreading to structurally adjacent areas. Indeed, initial damage to a given brain area was shown to disrupt the communication in related brain networks. Using cortico-striatal neuronal networks reconstructed in a microfluidic environment, we investigated the role of glutamate signaling in activity-dependent neuronal survival and trans-synaptic degeneration processes. Using a variety of neuronal insults applied on cortical neurons, we demonstrate that acute injuries such as axonal trauma, focal ischemia, or alteration of neuronal rhythms, lead to glutamate-dependent striatal neuron dysfunction. Interestingly, focal pro-oxidant insults or chronic alteration of spontaneous cortical rhythms provoked dysfunction of distant striatal neurons through abnormal glutamate GluN2B-NMDAR-mediated signaling at cortico-striatal synapses. These results indicate that focal alteration of cortical functions can initiate spreading of dysfunction along neuronal pathways in the brain, reminiscent of diaschisis-like processes. Nature Publishing Group UK 2018-08-02 /pmc/articles/PMC6072786/ /pubmed/30072750 http://dx.doi.org/10.1038/s41598-018-29918-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Deleglise, Bérangère
Lassus, Benjamin
Soubeyre, Vanessa
Doulazmi, Mohamed
Brugg, Bernard
Vanhoutte, Peter
Peyrin, Jean-Michel
Dysregulated Neurotransmission induces Trans-synaptic degeneration in reconstructed Neuronal Networks
title Dysregulated Neurotransmission induces Trans-synaptic degeneration in reconstructed Neuronal Networks
title_full Dysregulated Neurotransmission induces Trans-synaptic degeneration in reconstructed Neuronal Networks
title_fullStr Dysregulated Neurotransmission induces Trans-synaptic degeneration in reconstructed Neuronal Networks
title_full_unstemmed Dysregulated Neurotransmission induces Trans-synaptic degeneration in reconstructed Neuronal Networks
title_short Dysregulated Neurotransmission induces Trans-synaptic degeneration in reconstructed Neuronal Networks
title_sort dysregulated neurotransmission induces trans-synaptic degeneration in reconstructed neuronal networks
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072786/
https://www.ncbi.nlm.nih.gov/pubmed/30072750
http://dx.doi.org/10.1038/s41598-018-29918-1
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