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Hyaluronan-based extracellular matrix under conditions of homeostatic plasticity

Neuronal networks are balanced by mechanisms of homeostatic plasticity, which adjusts synaptic strength via molecular and morphological changes in the pre- and post-synapse. Here, we wondered whether the hyaluronic acid-based extracellular matrix (ECM) of the brain is involved in mechanisms of homeo...

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Autores principales: Valenzuela, Juan Carlos, Heise, Christopher, Franken, Gilbert, Singh, Jeet, Schweitzer, Barbara, Seidenbecher, Constanze I., Frischknecht, Renato
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173291/
https://www.ncbi.nlm.nih.gov/pubmed/25225099
http://dx.doi.org/10.1098/rstb.2013.0606
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author Valenzuela, Juan Carlos
Heise, Christopher
Franken, Gilbert
Singh, Jeet
Schweitzer, Barbara
Seidenbecher, Constanze I.
Frischknecht, Renato
author_facet Valenzuela, Juan Carlos
Heise, Christopher
Franken, Gilbert
Singh, Jeet
Schweitzer, Barbara
Seidenbecher, Constanze I.
Frischknecht, Renato
author_sort Valenzuela, Juan Carlos
collection PubMed
description Neuronal networks are balanced by mechanisms of homeostatic plasticity, which adjusts synaptic strength via molecular and morphological changes in the pre- and post-synapse. Here, we wondered whether the hyaluronic acid-based extracellular matrix (ECM) of the brain is involved in mechanisms of homeostatic plasticity. We hypothesized that the ECM, being rich in chondroitin sulfate proteoglycans such as brevican, which are suggested to stabilize synapses by their inhibitory effect on structural plasticity, must be remodelled to allow for structural and molecular changes during conditions of homeostatic plasticity. We found a high abundance of cleaved brevican fragments throughout the hippocampus and cortex and in neuronal cultures, with the strongest labelling in perineuronal nets on parvalbumin-positive interneurons. Using an antibody specific for a brevican fragment cleaved by the matrix metalloprotease ADAMTS4, we identified the enzyme as the main brevican-processing protease. Interestingly, we found ADAMTS4 largely associated with synapses. After inducing homeostatic plasticity in neuronal cell cultures by prolonged network inactivation, we found increased brevican processing at inhibitory as well as excitatory synapses, which is in line with the ADAMTS4 subcellular localization. Thus, the ECM is remodelled in conditions of homeostatic plasticity, which may liberate synapses to allow for a higher degree of structural plasticity.
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spelling pubmed-41732912014-10-19 Hyaluronan-based extracellular matrix under conditions of homeostatic plasticity Valenzuela, Juan Carlos Heise, Christopher Franken, Gilbert Singh, Jeet Schweitzer, Barbara Seidenbecher, Constanze I. Frischknecht, Renato Philos Trans R Soc Lond B Biol Sci Articles Neuronal networks are balanced by mechanisms of homeostatic plasticity, which adjusts synaptic strength via molecular and morphological changes in the pre- and post-synapse. Here, we wondered whether the hyaluronic acid-based extracellular matrix (ECM) of the brain is involved in mechanisms of homeostatic plasticity. We hypothesized that the ECM, being rich in chondroitin sulfate proteoglycans such as brevican, which are suggested to stabilize synapses by their inhibitory effect on structural plasticity, must be remodelled to allow for structural and molecular changes during conditions of homeostatic plasticity. We found a high abundance of cleaved brevican fragments throughout the hippocampus and cortex and in neuronal cultures, with the strongest labelling in perineuronal nets on parvalbumin-positive interneurons. Using an antibody specific for a brevican fragment cleaved by the matrix metalloprotease ADAMTS4, we identified the enzyme as the main brevican-processing protease. Interestingly, we found ADAMTS4 largely associated with synapses. After inducing homeostatic plasticity in neuronal cell cultures by prolonged network inactivation, we found increased brevican processing at inhibitory as well as excitatory synapses, which is in line with the ADAMTS4 subcellular localization. Thus, the ECM is remodelled in conditions of homeostatic plasticity, which may liberate synapses to allow for a higher degree of structural plasticity. The Royal Society 2014-10-19 /pmc/articles/PMC4173291/ /pubmed/25225099 http://dx.doi.org/10.1098/rstb.2013.0606 Text en http://creativecommons.org/licenses/by/4.0/ © 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Articles
Valenzuela, Juan Carlos
Heise, Christopher
Franken, Gilbert
Singh, Jeet
Schweitzer, Barbara
Seidenbecher, Constanze I.
Frischknecht, Renato
Hyaluronan-based extracellular matrix under conditions of homeostatic plasticity
title Hyaluronan-based extracellular matrix under conditions of homeostatic plasticity
title_full Hyaluronan-based extracellular matrix under conditions of homeostatic plasticity
title_fullStr Hyaluronan-based extracellular matrix under conditions of homeostatic plasticity
title_full_unstemmed Hyaluronan-based extracellular matrix under conditions of homeostatic plasticity
title_short Hyaluronan-based extracellular matrix under conditions of homeostatic plasticity
title_sort hyaluronan-based extracellular matrix under conditions of homeostatic plasticity
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173291/
https://www.ncbi.nlm.nih.gov/pubmed/25225099
http://dx.doi.org/10.1098/rstb.2013.0606
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