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Different Methods for Evaluating Microglial Activation Using Anti-Ionized Calcium-Binding Adaptor Protein-1 Immunohistochemistry in the Cuprizone Model

Microglia play an important role in the pathology of various central nervous system disorders, including multiple sclerosis (MS). While different methods exist to evaluate the extent of microglia activation, comparative studies investigating the sensitivity of these methods are missing for most mode...

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Autores principales: Wittekindt, Mariela, Kaddatz, Hannes, Joost, Sarah, Staffeld, Anna, Bitar, Yamen, Kipp, Markus, Frintrop, Linda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179561/
https://www.ncbi.nlm.nih.gov/pubmed/35681418
http://dx.doi.org/10.3390/cells11111723
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author Wittekindt, Mariela
Kaddatz, Hannes
Joost, Sarah
Staffeld, Anna
Bitar, Yamen
Kipp, Markus
Frintrop, Linda
author_facet Wittekindt, Mariela
Kaddatz, Hannes
Joost, Sarah
Staffeld, Anna
Bitar, Yamen
Kipp, Markus
Frintrop, Linda
author_sort Wittekindt, Mariela
collection PubMed
description Microglia play an important role in the pathology of various central nervous system disorders, including multiple sclerosis (MS). While different methods exist to evaluate the extent of microglia activation, comparative studies investigating the sensitivity of these methods are missing for most models. In this study, we systematically evaluated which of the three commonly used histological methods (id est, quantification of microglia density, densitometrically evaluated staining intensity, or cellular morphology based on the determination of a ramification index, all measured in anti-ionized calcium-binding adaptor protein-1 (IBA1) immunohistochemical stains) is the most sensitive method to detect subtle changes in the microglia activation status in the context of MS. To this end, we used the toxin-induced cuprizone model which allows the experimental induction of a highly reproducible demyelination in several central nervous system regions, paralleled by early microglia activation. In this study, we showed that after 3 weeks of cuprizone intoxication, all methods reveal a significant microglia activation in the white matter corpus callosum. In contrast, in the affected neocortical grey matter, the evaluation of anti-IBA1 cell morphologies was the most sensitive method to detect subtle changes of microglial activation. The results of this study provide a useful guide for future immunohistochemical evaluations in the cuprizone and other neurodegenerative models.
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spelling pubmed-91795612022-06-10 Different Methods for Evaluating Microglial Activation Using Anti-Ionized Calcium-Binding Adaptor Protein-1 Immunohistochemistry in the Cuprizone Model Wittekindt, Mariela Kaddatz, Hannes Joost, Sarah Staffeld, Anna Bitar, Yamen Kipp, Markus Frintrop, Linda Cells Article Microglia play an important role in the pathology of various central nervous system disorders, including multiple sclerosis (MS). While different methods exist to evaluate the extent of microglia activation, comparative studies investigating the sensitivity of these methods are missing for most models. In this study, we systematically evaluated which of the three commonly used histological methods (id est, quantification of microglia density, densitometrically evaluated staining intensity, or cellular morphology based on the determination of a ramification index, all measured in anti-ionized calcium-binding adaptor protein-1 (IBA1) immunohistochemical stains) is the most sensitive method to detect subtle changes in the microglia activation status in the context of MS. To this end, we used the toxin-induced cuprizone model which allows the experimental induction of a highly reproducible demyelination in several central nervous system regions, paralleled by early microglia activation. In this study, we showed that after 3 weeks of cuprizone intoxication, all methods reveal a significant microglia activation in the white matter corpus callosum. In contrast, in the affected neocortical grey matter, the evaluation of anti-IBA1 cell morphologies was the most sensitive method to detect subtle changes of microglial activation. The results of this study provide a useful guide for future immunohistochemical evaluations in the cuprizone and other neurodegenerative models. MDPI 2022-05-24 /pmc/articles/PMC9179561/ /pubmed/35681418 http://dx.doi.org/10.3390/cells11111723 Text en © 2022 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
Wittekindt, Mariela
Kaddatz, Hannes
Joost, Sarah
Staffeld, Anna
Bitar, Yamen
Kipp, Markus
Frintrop, Linda
Different Methods for Evaluating Microglial Activation Using Anti-Ionized Calcium-Binding Adaptor Protein-1 Immunohistochemistry in the Cuprizone Model
title Different Methods for Evaluating Microglial Activation Using Anti-Ionized Calcium-Binding Adaptor Protein-1 Immunohistochemistry in the Cuprizone Model
title_full Different Methods for Evaluating Microglial Activation Using Anti-Ionized Calcium-Binding Adaptor Protein-1 Immunohistochemistry in the Cuprizone Model
title_fullStr Different Methods for Evaluating Microglial Activation Using Anti-Ionized Calcium-Binding Adaptor Protein-1 Immunohistochemistry in the Cuprizone Model
title_full_unstemmed Different Methods for Evaluating Microglial Activation Using Anti-Ionized Calcium-Binding Adaptor Protein-1 Immunohistochemistry in the Cuprizone Model
title_short Different Methods for Evaluating Microglial Activation Using Anti-Ionized Calcium-Binding Adaptor Protein-1 Immunohistochemistry in the Cuprizone Model
title_sort different methods for evaluating microglial activation using anti-ionized calcium-binding adaptor protein-1 immunohistochemistry in the cuprizone model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179561/
https://www.ncbi.nlm.nih.gov/pubmed/35681418
http://dx.doi.org/10.3390/cells11111723
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