Reversible Loss of Hippocampal Function in a Mouse Model of Demyelination/Remyelination
Demyelination of axons in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS) and other demyelinating diseases. Cycles of demyelination, followed by remyelination, appear in the majority of MS patients and are associated with the onset and quiescence of disease-related symptoms...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987410/ https://www.ncbi.nlm.nih.gov/pubmed/32038176 http://dx.doi.org/10.3389/fncel.2019.00588 |
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author | Das, Aniruddha Bastian, Chinthasagar Trestan, Lexie Suh, Jason Dey, Tanujit Trapp, Bruce D. Baltan, Selva Dana, Hod |
author_facet | Das, Aniruddha Bastian, Chinthasagar Trestan, Lexie Suh, Jason Dey, Tanujit Trapp, Bruce D. Baltan, Selva Dana, Hod |
author_sort | Das, Aniruddha |
collection | PubMed |
description | Demyelination of axons in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS) and other demyelinating diseases. Cycles of demyelination, followed by remyelination, appear in the majority of MS patients and are associated with the onset and quiescence of disease-related symptoms, respectively. Previous studies in human patients and animal models have shown that vast demyelination is accompanied by wide-scale changes to brain activity, but details of this process are poorly understood. We used electrophysiological recordings and non-linear fluorescence imaging from genetically encoded calcium indicators to monitor the activity of hippocampal neurons during demyelination and remyelination over a period of 100 days. We found that synaptic transmission in CA1 neurons was diminished in vitro, and that neuronal firing rates in CA1 and the dentate gyrus (DG) were substantially reduced during demyelination in vivo, which partially recovered after a short remyelination period. This new approach allows monitoring how changes in synaptic transmission induced by cuprizone diet affect neuronal activity, and it can potentially be used to study the effects of therapeutic interventions in protecting the functionality of CNS neurons. |
format | Online Article Text |
id | pubmed-6987410 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69874102020-02-07 Reversible Loss of Hippocampal Function in a Mouse Model of Demyelination/Remyelination Das, Aniruddha Bastian, Chinthasagar Trestan, Lexie Suh, Jason Dey, Tanujit Trapp, Bruce D. Baltan, Selva Dana, Hod Front Cell Neurosci Neuroscience Demyelination of axons in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS) and other demyelinating diseases. Cycles of demyelination, followed by remyelination, appear in the majority of MS patients and are associated with the onset and quiescence of disease-related symptoms, respectively. Previous studies in human patients and animal models have shown that vast demyelination is accompanied by wide-scale changes to brain activity, but details of this process are poorly understood. We used electrophysiological recordings and non-linear fluorescence imaging from genetically encoded calcium indicators to monitor the activity of hippocampal neurons during demyelination and remyelination over a period of 100 days. We found that synaptic transmission in CA1 neurons was diminished in vitro, and that neuronal firing rates in CA1 and the dentate gyrus (DG) were substantially reduced during demyelination in vivo, which partially recovered after a short remyelination period. This new approach allows monitoring how changes in synaptic transmission induced by cuprizone diet affect neuronal activity, and it can potentially be used to study the effects of therapeutic interventions in protecting the functionality of CNS neurons. Frontiers Media S.A. 2020-01-22 /pmc/articles/PMC6987410/ /pubmed/32038176 http://dx.doi.org/10.3389/fncel.2019.00588 Text en Copyright © 2020 Das, Bastian, Trestan, Suh, Dey, Trapp, Baltan and Dana. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Das, Aniruddha Bastian, Chinthasagar Trestan, Lexie Suh, Jason Dey, Tanujit Trapp, Bruce D. Baltan, Selva Dana, Hod Reversible Loss of Hippocampal Function in a Mouse Model of Demyelination/Remyelination |
title | Reversible Loss of Hippocampal Function in a Mouse Model of Demyelination/Remyelination |
title_full | Reversible Loss of Hippocampal Function in a Mouse Model of Demyelination/Remyelination |
title_fullStr | Reversible Loss of Hippocampal Function in a Mouse Model of Demyelination/Remyelination |
title_full_unstemmed | Reversible Loss of Hippocampal Function in a Mouse Model of Demyelination/Remyelination |
title_short | Reversible Loss of Hippocampal Function in a Mouse Model of Demyelination/Remyelination |
title_sort | reversible loss of hippocampal function in a mouse model of demyelination/remyelination |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987410/ https://www.ncbi.nlm.nih.gov/pubmed/32038176 http://dx.doi.org/10.3389/fncel.2019.00588 |
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