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Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice

The extracellular matrix (ECM) plays a key role in synaptogenesis and the regulation of synaptic functions in the central nervous system. Recent studies revealed that in addition to dopaminergic and serotoninergic neuromodulatory systems, microglia also contribute to the regulation of ECM remodeling...

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Autores principales: Strackeljan, Luisa, Baczynska, Ewa, Cangalaya, Carla, Baidoe-Ansah, David, Wlodarczyk, Jakub, Kaushik, Rahul, Dityatev, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393852/
https://www.ncbi.nlm.nih.gov/pubmed/34440631
http://dx.doi.org/10.3390/cells10081862
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author Strackeljan, Luisa
Baczynska, Ewa
Cangalaya, Carla
Baidoe-Ansah, David
Wlodarczyk, Jakub
Kaushik, Rahul
Dityatev, Alexander
author_facet Strackeljan, Luisa
Baczynska, Ewa
Cangalaya, Carla
Baidoe-Ansah, David
Wlodarczyk, Jakub
Kaushik, Rahul
Dityatev, Alexander
author_sort Strackeljan, Luisa
collection PubMed
description The extracellular matrix (ECM) plays a key role in synaptogenesis and the regulation of synaptic functions in the central nervous system. Recent studies revealed that in addition to dopaminergic and serotoninergic neuromodulatory systems, microglia also contribute to the regulation of ECM remodeling. In the present work, we investigated the physiological role of microglia in the remodeling of perineuronal nets (PNNs), predominantly associated with parvalbumin-immunopositive (PV+) interneurons, and the perisynaptic ECM around pyramidal neurons in the hippocampus. Adult mice were treated with PLX3397 (pexidartinib), as the inhibitor of colony-stimulating factor 1 receptor (CSF1-R), to deplete microglia. Then, confocal analysis of the ECM and synapses was performed. Although the elimination of microglia did not alter the overall number or intensity of PNNs in the CA1 region of the hippocampus, it decreased the size of PNN holes and elevated the expression of the surrounding ECM. In the neuropil area in the CA1 str. radiatum, the depletion of microglia increased the expression of perisynaptic ECM proteoglycan brevican, which was accompanied by the elevated expression of presynaptic marker vGluT1 and the increased density of dendritic spines. Thus, microglia regulate the homeostasis of pre- and postsynaptic excitatory terminals and the surrounding perisynaptic ECM as well as the fine structure of PNNs enveloping perisomatic—predominantly GABAergic—synapses.
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spelling pubmed-83938522021-08-28 Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice Strackeljan, Luisa Baczynska, Ewa Cangalaya, Carla Baidoe-Ansah, David Wlodarczyk, Jakub Kaushik, Rahul Dityatev, Alexander Cells Article The extracellular matrix (ECM) plays a key role in synaptogenesis and the regulation of synaptic functions in the central nervous system. Recent studies revealed that in addition to dopaminergic and serotoninergic neuromodulatory systems, microglia also contribute to the regulation of ECM remodeling. In the present work, we investigated the physiological role of microglia in the remodeling of perineuronal nets (PNNs), predominantly associated with parvalbumin-immunopositive (PV+) interneurons, and the perisynaptic ECM around pyramidal neurons in the hippocampus. Adult mice were treated with PLX3397 (pexidartinib), as the inhibitor of colony-stimulating factor 1 receptor (CSF1-R), to deplete microglia. Then, confocal analysis of the ECM and synapses was performed. Although the elimination of microglia did not alter the overall number or intensity of PNNs in the CA1 region of the hippocampus, it decreased the size of PNN holes and elevated the expression of the surrounding ECM. In the neuropil area in the CA1 str. radiatum, the depletion of microglia increased the expression of perisynaptic ECM proteoglycan brevican, which was accompanied by the elevated expression of presynaptic marker vGluT1 and the increased density of dendritic spines. Thus, microglia regulate the homeostasis of pre- and postsynaptic excitatory terminals and the surrounding perisynaptic ECM as well as the fine structure of PNNs enveloping perisomatic—predominantly GABAergic—synapses. MDPI 2021-07-22 /pmc/articles/PMC8393852/ /pubmed/34440631 http://dx.doi.org/10.3390/cells10081862 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Strackeljan, Luisa
Baczynska, Ewa
Cangalaya, Carla
Baidoe-Ansah, David
Wlodarczyk, Jakub
Kaushik, Rahul
Dityatev, Alexander
Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice
title Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice
title_full Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice
title_fullStr Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice
title_full_unstemmed Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice
title_short Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice
title_sort microglia depletion-induced remodeling of extracellular matrix and excitatory synapses in the hippocampus of adult mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393852/
https://www.ncbi.nlm.nih.gov/pubmed/34440631
http://dx.doi.org/10.3390/cells10081862
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