Novel cell-based analysis reveals region-dependent changes in microglial dynamics in grey matter in a cuprizone model of demyelination
Microglia are key players in Multiple Sclerosis (MS), expressing many susceptibility genes for this disease. They constantly survey the brain microenvironment, but the precise functional relationships between microglia and pathological processes remain unknown. We performed a detailed assessment of...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996121001984 |
| _version_ | 1818596888056692736 |
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| author | Ilias Roufagalas Maria Avloniti Alexandra Fortosi Evangelia Xingi Dimitra Thomaidou Lesley Probert Vasiliki Kyrargyri |
| author_facet | Ilias Roufagalas Maria Avloniti Alexandra Fortosi Evangelia Xingi Dimitra Thomaidou Lesley Probert Vasiliki Kyrargyri |
| author_sort | Ilias Roufagalas |
| collection | DOAJ |
| description | Microglia are key players in Multiple Sclerosis (MS), expressing many susceptibility genes for this disease. They constantly survey the brain microenvironment, but the precise functional relationships between microglia and pathological processes remain unknown. We performed a detailed assessment of microglial dynamics in three distinct grey matter regions in a cuprizone-induced demyelination model. We found that microglial activation preceded detectable demyelination and showed regional specificities, such as prominent phagocytic activity in cortical layer 5 and early hypertrophic morphology in hippocampal CA1. Demyelination happened earliest in cortical layer 5, although was more complete in CA1. In cortical layer 2/3, microglial activation and demyelination were less pronounced but microglia became hyper-ramified with slower process movement during remyelination, thereby maintaining local brain surveillance. Profiling of microglia using specific morphological and motility parameters revealed region-specific heterogeneity of microglial responses in the grey matter that might serve as sensitive indicators of progression in CNS demyelinating diseases. |
| first_indexed | 2024-12-16T11:39:04Z |
| format | Article |
| id | doaj.art-4942f21d41f64628929d2760d9a96963 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T11:39:04Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-4942f21d41f64628929d2760d9a969632022-12-21T22:33:00ZengElsevierNeurobiology of Disease1095-953X2021-09-01157105449Novel cell-based analysis reveals region-dependent changes in microglial dynamics in grey matter in a cuprizone model of demyelinationIlias Roufagalas0Maria Avloniti1Alexandra Fortosi2Evangelia Xingi3Dimitra Thomaidou4Lesley Probert5Vasiliki Kyrargyri6Department of Immunology, Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, GreeceDepartment of Immunology, Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, GreeceDepartment of Immunology, Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, GreeceLight Microscopy Unit, Hellenic Pasteur Institute, Athens, GreeceLight Microscopy Unit, Hellenic Pasteur Institute, Athens, Greece; Department of Neurobiology, Neural Stem Cells & Neuroimaging Group, Hellenic Pasteur Institute, Athens, GreeceDepartment of Immunology, Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, GreeceDepartment of Immunology, Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece; Corresponding author.Microglia are key players in Multiple Sclerosis (MS), expressing many susceptibility genes for this disease. They constantly survey the brain microenvironment, but the precise functional relationships between microglia and pathological processes remain unknown. We performed a detailed assessment of microglial dynamics in three distinct grey matter regions in a cuprizone-induced demyelination model. We found that microglial activation preceded detectable demyelination and showed regional specificities, such as prominent phagocytic activity in cortical layer 5 and early hypertrophic morphology in hippocampal CA1. Demyelination happened earliest in cortical layer 5, although was more complete in CA1. In cortical layer 2/3, microglial activation and demyelination were less pronounced but microglia became hyper-ramified with slower process movement during remyelination, thereby maintaining local brain surveillance. Profiling of microglia using specific morphological and motility parameters revealed region-specific heterogeneity of microglial responses in the grey matter that might serve as sensitive indicators of progression in CNS demyelinating diseases.http://www.sciencedirect.com/science/article/pii/S0969996121001984MicroAppMicroglia heterogeneityBrain surveillance2-photon imagingDemyelinationCuprizone |
| spellingShingle | Ilias Roufagalas Maria Avloniti Alexandra Fortosi Evangelia Xingi Dimitra Thomaidou Lesley Probert Vasiliki Kyrargyri Novel cell-based analysis reveals region-dependent changes in microglial dynamics in grey matter in a cuprizone model of demyelination Neurobiology of Disease MicroApp Microglia heterogeneity Brain surveillance 2-photon imaging Demyelination Cuprizone |
| title | Novel cell-based analysis reveals region-dependent changes in microglial dynamics in grey matter in a cuprizone model of demyelination |
| title_full | Novel cell-based analysis reveals region-dependent changes in microglial dynamics in grey matter in a cuprizone model of demyelination |
| title_fullStr | Novel cell-based analysis reveals region-dependent changes in microglial dynamics in grey matter in a cuprizone model of demyelination |
| title_full_unstemmed | Novel cell-based analysis reveals region-dependent changes in microglial dynamics in grey matter in a cuprizone model of demyelination |
| title_short | Novel cell-based analysis reveals region-dependent changes in microglial dynamics in grey matter in a cuprizone model of demyelination |
| title_sort | novel cell based analysis reveals region dependent changes in microglial dynamics in grey matter in a cuprizone model of demyelination |
| topic | MicroApp Microglia heterogeneity Brain surveillance 2-photon imaging Demyelination Cuprizone |
| url | http://www.sciencedirect.com/science/article/pii/S0969996121001984 |
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