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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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