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Glia from the central and peripheral nervous system are differentially affected by paclitaxel chemotherapy via modulating their neuroinflammatory and neuroregenerative properties

Glia are critical players in defining synaptic contacts and maintaining neuronal homeostasis. Both astrocytes as glia of the central nervous system (CNS), as well as satellite glial cells (SGC) as glia of the peripheral nervous system (PNS), intimately interact with microglia, especially under patho...

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Autores principales: Klein, Ines, Boenert, Janne, Lange, Felix, Christensen, Britt, Wassermann, Meike K., Wiesen, Martin H. J., Olschewski, Daniel Navin, Rabenstein, Monika, Müller, Carsten, Lehmann, Helmar C., Fink, Gereon Rudolf, Schroeter, Michael, Rueger, Maria Adele, Vay, Sabine Ulrike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9666700/
https://www.ncbi.nlm.nih.gov/pubmed/36408236
http://dx.doi.org/10.3389/fphar.2022.1038285
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author Klein, Ines
Boenert, Janne
Lange, Felix
Christensen, Britt
Wassermann, Meike K.
Wiesen, Martin H. J.
Olschewski, Daniel Navin
Rabenstein, Monika
Müller, Carsten
Lehmann, Helmar C.
Fink, Gereon Rudolf
Schroeter, Michael
Rueger, Maria Adele
Vay, Sabine Ulrike
author_facet Klein, Ines
Boenert, Janne
Lange, Felix
Christensen, Britt
Wassermann, Meike K.
Wiesen, Martin H. J.
Olschewski, Daniel Navin
Rabenstein, Monika
Müller, Carsten
Lehmann, Helmar C.
Fink, Gereon Rudolf
Schroeter, Michael
Rueger, Maria Adele
Vay, Sabine Ulrike
author_sort Klein, Ines
collection PubMed
description Glia are critical players in defining synaptic contacts and maintaining neuronal homeostasis. Both astrocytes as glia of the central nervous system (CNS), as well as satellite glial cells (SGC) as glia of the peripheral nervous system (PNS), intimately interact with microglia, especially under pathological conditions when glia regulate degenerative as well as regenerative processes. The chemotherapeutic agent paclitaxel evokes peripheral neuropathy and cognitive deficits; however, the mechanisms underlying these diverse clinical side effects are unclear. We aimed to elucidate the direct effects of paclitaxel on the function of astrocytes, microglia, and SGCs, and their glia-glia and neuronal-glia interactions. After intravenous application, paclitaxel was present in the dorsal root ganglia of the PNS and the CNS of rodents. In vitro, SGC enhanced the expression of pro-inflammatory factors and reduced the expression of neurotrophic factor NT-3 upon exposure to paclitaxel, resulting in predominantly neurotoxic effects. Likewise, paclitaxel induced a switch towards a pro-inflammatory phenotype in microglia, exerting neurotoxicity. In contrast, astrocytes expressed neuroprotective markers and increasingly expressed S100A10 after paclitaxel exposure. Astrocytes, and to a lesser extent SGCs, had regulatory effects on microglia independent of paclitaxel exposure. Data suggest that paclitaxel differentially modulates glia cells regarding their (neuro-) inflammatory and (neuro-) regenerative properties and also affects their interaction. By elucidating those processes, our data contribute to the understanding of the mechanistic pathways of paclitaxel-induced side effects in CNS and PNS.
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spelling pubmed-96667002022-11-17 Glia from the central and peripheral nervous system are differentially affected by paclitaxel chemotherapy via modulating their neuroinflammatory and neuroregenerative properties Klein, Ines Boenert, Janne Lange, Felix Christensen, Britt Wassermann, Meike K. Wiesen, Martin H. J. Olschewski, Daniel Navin Rabenstein, Monika Müller, Carsten Lehmann, Helmar C. Fink, Gereon Rudolf Schroeter, Michael Rueger, Maria Adele Vay, Sabine Ulrike Front Pharmacol Pharmacology Glia are critical players in defining synaptic contacts and maintaining neuronal homeostasis. Both astrocytes as glia of the central nervous system (CNS), as well as satellite glial cells (SGC) as glia of the peripheral nervous system (PNS), intimately interact with microglia, especially under pathological conditions when glia regulate degenerative as well as regenerative processes. The chemotherapeutic agent paclitaxel evokes peripheral neuropathy and cognitive deficits; however, the mechanisms underlying these diverse clinical side effects are unclear. We aimed to elucidate the direct effects of paclitaxel on the function of astrocytes, microglia, and SGCs, and their glia-glia and neuronal-glia interactions. After intravenous application, paclitaxel was present in the dorsal root ganglia of the PNS and the CNS of rodents. In vitro, SGC enhanced the expression of pro-inflammatory factors and reduced the expression of neurotrophic factor NT-3 upon exposure to paclitaxel, resulting in predominantly neurotoxic effects. Likewise, paclitaxel induced a switch towards a pro-inflammatory phenotype in microglia, exerting neurotoxicity. In contrast, astrocytes expressed neuroprotective markers and increasingly expressed S100A10 after paclitaxel exposure. Astrocytes, and to a lesser extent SGCs, had regulatory effects on microglia independent of paclitaxel exposure. Data suggest that paclitaxel differentially modulates glia cells regarding their (neuro-) inflammatory and (neuro-) regenerative properties and also affects their interaction. By elucidating those processes, our data contribute to the understanding of the mechanistic pathways of paclitaxel-induced side effects in CNS and PNS. Frontiers Media S.A. 2022-11-02 /pmc/articles/PMC9666700/ /pubmed/36408236 http://dx.doi.org/10.3389/fphar.2022.1038285 Text en Copyright © 2022 Klein, Boenert, Lange, Christensen, Wassermann, Wiesen, Olschewski, Rabenstein, Müller, Lehmann, Fink, Schroeter, Rueger and Vay. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Klein, Ines
Boenert, Janne
Lange, Felix
Christensen, Britt
Wassermann, Meike K.
Wiesen, Martin H. J.
Olschewski, Daniel Navin
Rabenstein, Monika
Müller, Carsten
Lehmann, Helmar C.
Fink, Gereon Rudolf
Schroeter, Michael
Rueger, Maria Adele
Vay, Sabine Ulrike
Glia from the central and peripheral nervous system are differentially affected by paclitaxel chemotherapy via modulating their neuroinflammatory and neuroregenerative properties
title Glia from the central and peripheral nervous system are differentially affected by paclitaxel chemotherapy via modulating their neuroinflammatory and neuroregenerative properties
title_full Glia from the central and peripheral nervous system are differentially affected by paclitaxel chemotherapy via modulating their neuroinflammatory and neuroregenerative properties
title_fullStr Glia from the central and peripheral nervous system are differentially affected by paclitaxel chemotherapy via modulating their neuroinflammatory and neuroregenerative properties
title_full_unstemmed Glia from the central and peripheral nervous system are differentially affected by paclitaxel chemotherapy via modulating their neuroinflammatory and neuroregenerative properties
title_short Glia from the central and peripheral nervous system are differentially affected by paclitaxel chemotherapy via modulating their neuroinflammatory and neuroregenerative properties
title_sort glia from the central and peripheral nervous system are differentially affected by paclitaxel chemotherapy via modulating their neuroinflammatory and neuroregenerative properties
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9666700/
https://www.ncbi.nlm.nih.gov/pubmed/36408236
http://dx.doi.org/10.3389/fphar.2022.1038285
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