Hyaluronidase-induced matrix remodeling contributes to long-term synaptic changes

Extracellular brain space contains water, dissolved ions, and multiple other signaling molecules. The neural extracellular matrix (ECM) is also a significant component of the extracellular space. The ECM is synthesized by neurons, astrocytes, and other types of cells. Hyaluronan, a hyaluronic acid p...

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Main Authors: Rostislav Sokolov, Viktoriya Krut', Vsevolod Belousov, Andrey Rozov, Irina V. Mukhina
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Neural Circuits
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Online Access:https://www.frontiersin.org/articles/10.3389/fncir.2024.1441280/full
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author Rostislav Sokolov
Rostislav Sokolov
Viktoriya Krut'
Viktoriya Krut'
Vsevolod Belousov
Vsevolod Belousov
Vsevolod Belousov
Vsevolod Belousov
Andrey Rozov
Andrey Rozov
Irina V. Mukhina
Irina V. Mukhina
author_facet Rostislav Sokolov
Rostislav Sokolov
Viktoriya Krut'
Viktoriya Krut'
Vsevolod Belousov
Vsevolod Belousov
Vsevolod Belousov
Vsevolod Belousov
Andrey Rozov
Andrey Rozov
Irina V. Mukhina
Irina V. Mukhina
author_sort Rostislav Sokolov
collection DOAJ
description Extracellular brain space contains water, dissolved ions, and multiple other signaling molecules. The neural extracellular matrix (ECM) is also a significant component of the extracellular space. The ECM is synthesized by neurons, astrocytes, and other types of cells. Hyaluronan, a hyaluronic acid polymer, is a key component of the ECM. The functions of hyaluronan include barrier functions and signaling. In this article, we investigate physiological processes during the acute phase of enzymatic ECM removal. We found that hyaluronidase, an ECM removal agent, triggers simultaneous membrane depolarization and sharp calcium influx into neurons. Spontaneous action potential firing frequency increased rapidly after ECM destruction in interneurons, but not pyramidal neurons. Hyaluronidase-dependent calcium entry can be blocked by a selective antagonist of N-methyl-D-aspartate (NMDA) receptors, revealing these receptors as the main player in the observed phenomenon. Additionally, we demonstrate increased NMDA-dependent long-term potentiation at CA3-to-CA1 synapses during the acute phase of ECM removal. These findings suggest that hyaluronan is a significant synaptic player.
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spelling doaj-art-a073f6b9407248eaa94cbaa3342fbaf92025-01-17T06:50:47ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102025-01-011810.3389/fncir.2024.14412801441280Hyaluronidase-induced matrix remodeling contributes to long-term synaptic changesRostislav Sokolov0Rostislav Sokolov1Viktoriya Krut'2Viktoriya Krut'3Vsevolod Belousov4Vsevolod Belousov5Vsevolod Belousov6Vsevolod Belousov7Andrey Rozov8Andrey Rozov9Irina V. Mukhina10Irina V. Mukhina11Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, RussiaPirogov Russian National Research Medical University, Moscow, RussiaPirogov Russian National Research Medical University, Moscow, RussiaFederal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow, RussiaPirogov Russian National Research Medical University, Moscow, RussiaFederal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaLife Improvement by Future Technologies (LIFT) Center, Moscow, RussiaInstitute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, RussiaFederal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow, RussiaInstitute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, RussiaInstitute of Fundamental Medicine, Privolzhsky Research Medical University, Nizhny Novgorod, RussiaExtracellular brain space contains water, dissolved ions, and multiple other signaling molecules. The neural extracellular matrix (ECM) is also a significant component of the extracellular space. The ECM is synthesized by neurons, astrocytes, and other types of cells. Hyaluronan, a hyaluronic acid polymer, is a key component of the ECM. The functions of hyaluronan include barrier functions and signaling. In this article, we investigate physiological processes during the acute phase of enzymatic ECM removal. We found that hyaluronidase, an ECM removal agent, triggers simultaneous membrane depolarization and sharp calcium influx into neurons. Spontaneous action potential firing frequency increased rapidly after ECM destruction in interneurons, but not pyramidal neurons. Hyaluronidase-dependent calcium entry can be blocked by a selective antagonist of N-methyl-D-aspartate (NMDA) receptors, revealing these receptors as the main player in the observed phenomenon. Additionally, we demonstrate increased NMDA-dependent long-term potentiation at CA3-to-CA1 synapses during the acute phase of ECM removal. These findings suggest that hyaluronan is a significant synaptic player.https://www.frontiersin.org/articles/10.3389/fncir.2024.1441280/fullhippocampusextracellular matrixsynaptic plasticityNMDA receptorshyaluronidase
spellingShingle Rostislav Sokolov
Rostislav Sokolov
Viktoriya Krut'
Viktoriya Krut'
Vsevolod Belousov
Vsevolod Belousov
Vsevolod Belousov
Vsevolod Belousov
Andrey Rozov
Andrey Rozov
Irina V. Mukhina
Irina V. Mukhina
Hyaluronidase-induced matrix remodeling contributes to long-term synaptic changes
Frontiers in Neural Circuits
hippocampus
extracellular matrix
synaptic plasticity
NMDA receptors
hyaluronidase
title Hyaluronidase-induced matrix remodeling contributes to long-term synaptic changes
title_full Hyaluronidase-induced matrix remodeling contributes to long-term synaptic changes
title_fullStr Hyaluronidase-induced matrix remodeling contributes to long-term synaptic changes
title_full_unstemmed Hyaluronidase-induced matrix remodeling contributes to long-term synaptic changes
title_short Hyaluronidase-induced matrix remodeling contributes to long-term synaptic changes
title_sort hyaluronidase induced matrix remodeling contributes to long term synaptic changes
topic hippocampus
extracellular matrix
synaptic plasticity
NMDA receptors
hyaluronidase
url https://www.frontiersin.org/articles/10.3389/fncir.2024.1441280/full
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