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Astrocytic CD44 Deficiency Reduces the Severity of Kainate-Induced Epilepsy
Background: Epilepsy affects millions of people worldwide, yet we still lack a successful treatment for all epileptic patients. Most of the available drugs modulate neuronal activity. Astrocytes, the most abundant cells in the brain, may constitute alternative drug targets. A robust expansion of ast...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252631/ https://www.ncbi.nlm.nih.gov/pubmed/37296604 http://dx.doi.org/10.3390/cells12111483 |
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author | Kruk, Patrycja K. Nader, Karolina Skupien-Jaroszek, Anna Wójtowicz, Tomasz Buszka, Anna Olech-Kochańczyk, Gabriela Wilczynski, Grzegorz M. Worch, Remigiusz Kalita, Katarzyna Włodarczyk, Jakub Dzwonek, Joanna |
author_facet | Kruk, Patrycja K. Nader, Karolina Skupien-Jaroszek, Anna Wójtowicz, Tomasz Buszka, Anna Olech-Kochańczyk, Gabriela Wilczynski, Grzegorz M. Worch, Remigiusz Kalita, Katarzyna Włodarczyk, Jakub Dzwonek, Joanna |
author_sort | Kruk, Patrycja K. |
collection | PubMed |
description | Background: Epilepsy affects millions of people worldwide, yet we still lack a successful treatment for all epileptic patients. Most of the available drugs modulate neuronal activity. Astrocytes, the most abundant cells in the brain, may constitute alternative drug targets. A robust expansion of astrocytic cell bodies and processes occurs after seizures. Highly expressed in astrocytes, CD44 adhesion protein is upregulated during injury and is suggested to be one of the most important proteins associated with epilepsy. It connects the astrocytic cytoskeleton to hyaluronan in the extracellular matrix, influencing both structural and functional aspects of brain plasticity. Methods: Herein, we used transgenic mice with an astrocyte CD44 knockout to evaluate the impact of the hippocampal CD44 absence on the development of epileptogenesis and ultrastructural changes at the tripartite synapse. Results: We demonstrated that local, virally-induced CD44 deficiency in hippocampal astrocytes reduces reactive astrogliosis and decreases the progression of kainic acid-induced epileptogenesis. We also observed that CD44 deficiency resulted in structural changes evident in a higher dendritic spine number along with a lower percentage of astrocyte-synapse contacts, and decreased post-synaptic density size in the hippocampal molecular layer of the dentate gyrus. Conclusions: Overall, our study indicates that CD44 signaling may be important for astrocytic coverage of synapses in the hippocampus and that alterations of astrocytes translate to functional changes in the pathology of epilepsy. |
format | Online Article Text |
id | pubmed-10252631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102526312023-06-10 Astrocytic CD44 Deficiency Reduces the Severity of Kainate-Induced Epilepsy Kruk, Patrycja K. Nader, Karolina Skupien-Jaroszek, Anna Wójtowicz, Tomasz Buszka, Anna Olech-Kochańczyk, Gabriela Wilczynski, Grzegorz M. Worch, Remigiusz Kalita, Katarzyna Włodarczyk, Jakub Dzwonek, Joanna Cells Article Background: Epilepsy affects millions of people worldwide, yet we still lack a successful treatment for all epileptic patients. Most of the available drugs modulate neuronal activity. Astrocytes, the most abundant cells in the brain, may constitute alternative drug targets. A robust expansion of astrocytic cell bodies and processes occurs after seizures. Highly expressed in astrocytes, CD44 adhesion protein is upregulated during injury and is suggested to be one of the most important proteins associated with epilepsy. It connects the astrocytic cytoskeleton to hyaluronan in the extracellular matrix, influencing both structural and functional aspects of brain plasticity. Methods: Herein, we used transgenic mice with an astrocyte CD44 knockout to evaluate the impact of the hippocampal CD44 absence on the development of epileptogenesis and ultrastructural changes at the tripartite synapse. Results: We demonstrated that local, virally-induced CD44 deficiency in hippocampal astrocytes reduces reactive astrogliosis and decreases the progression of kainic acid-induced epileptogenesis. We also observed that CD44 deficiency resulted in structural changes evident in a higher dendritic spine number along with a lower percentage of astrocyte-synapse contacts, and decreased post-synaptic density size in the hippocampal molecular layer of the dentate gyrus. Conclusions: Overall, our study indicates that CD44 signaling may be important for astrocytic coverage of synapses in the hippocampus and that alterations of astrocytes translate to functional changes in the pathology of epilepsy. MDPI 2023-05-26 /pmc/articles/PMC10252631/ /pubmed/37296604 http://dx.doi.org/10.3390/cells12111483 Text en © 2023 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 Kruk, Patrycja K. Nader, Karolina Skupien-Jaroszek, Anna Wójtowicz, Tomasz Buszka, Anna Olech-Kochańczyk, Gabriela Wilczynski, Grzegorz M. Worch, Remigiusz Kalita, Katarzyna Włodarczyk, Jakub Dzwonek, Joanna Astrocytic CD44 Deficiency Reduces the Severity of Kainate-Induced Epilepsy |
title | Astrocytic CD44 Deficiency Reduces the Severity of Kainate-Induced Epilepsy |
title_full | Astrocytic CD44 Deficiency Reduces the Severity of Kainate-Induced Epilepsy |
title_fullStr | Astrocytic CD44 Deficiency Reduces the Severity of Kainate-Induced Epilepsy |
title_full_unstemmed | Astrocytic CD44 Deficiency Reduces the Severity of Kainate-Induced Epilepsy |
title_short | Astrocytic CD44 Deficiency Reduces the Severity of Kainate-Induced Epilepsy |
title_sort | astrocytic cd44 deficiency reduces the severity of kainate-induced epilepsy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252631/ https://www.ncbi.nlm.nih.gov/pubmed/37296604 http://dx.doi.org/10.3390/cells12111483 |
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