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...

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Autores principales: Das, Aniruddha, Bastian, Chinthasagar, Trestan, Lexie, Suh, Jason, Dey, Tanujit, Trapp, Bruce D., Baltan, Selva, Dana, Hod
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
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.
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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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