Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion
Neuroinflammation contributes to neuronal degeneration in Parkinson's disease (PD). However, how brain inflammatory factors mediate the progression of neurodegeneration is still poorly understood. Experimental models of PD have shed light on the understanding of this phenomenon, but the explora...
| Autores: | , , , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:258439 |
| Acesso em linha: | https://ddd.uab.cat/record/258439 https://dx.doi.org/urn:doi:10.1016/j.jneuroim.2022.577874 |
| Access Level: | acceso abierto |
| Palavra-chave: | Parkinson's disease Microglia Macrophages Lipopolysaccharide Phagocytosis Dopamine Neurodegeneration Experimental models |
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Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletionHeman-Bozadas, P.Romero, CarolinaMartínez-Remedios, P.Freitag, I.Frías, A.Saavedra-López, Elena|||0000-0001-9788-2414Casanova, Paola|||0000-0002-4814-0577Roig-Martínez, M.Cribaro, George Paul|||0000-0002-5251-1537Rovirosa-Hernández, M. J.Hernandez-Baltazar, D.Barcia, Carlos|||0000-0003-0976-4245Parkinson's diseaseMicrogliaMacrophagesLipopolysaccharidePhagocytosisDopamineNeurodegenerationExperimental modelsNeuroinflammation contributes to neuronal degeneration in Parkinson's disease (PD). However, how brain inflammatory factors mediate the progression of neurodegeneration is still poorly understood. Experimental models of PD have shed light on the understanding of this phenomenon, but the exploration of inflammation-driven models is necessary to better characterize this aspect of the disorder. The use of lipopolysaccharide (LPS) to induce a neuroinflammation-mediated neuronal loss is useful to induce reliable elimination of dopaminergic neurons. Nevertheless, how this model parallels the PD-like neuroinflammation is uncertain. In the present work, we used the direct LPS injection as a model inductor to eliminate dopaminergic neurons of the substantia nigra pars compacta (SNpc) in rats and reevaluated the inflammatory reaction. High-resolution 3D histological examination revealed that, although LPS induced a reliable elimination of SNpc dopaminergic neurons, it also generated a massive inflammatory response. This inflammation-mediated injury was characterized by corralling, a damaged parenchyma occupied by a vast population of lesion-associated microglia and macrophages (LAMMs) undertaking wound compaction and scar formation, surrounded by highly reactive astrocytes. LAMMs tiled the entire lesion and engaged in long-standing phagocytic activity to resolve the injury. Additionally, modeling LPS inflammation in a cell culture system helped to understand the role of phagocytosis and cytotoxicity in the initial phases of dopaminergic degeneration and indicated that LAMM-mediated toxicity and phagocytosis coexist during LPS-mediated dopaminergic elimination. However, this type of severe inflammatory-mediated injury, and subsequent resolution appear to be different from the ageing-related PD scenario where the architectural structure of the parenchyma is mostly preserved. Thus, the necessity to explore new experimental models to properly mimic the inflammatory compound observed in PD degeneration. 22022-01-0120222022-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/258439https://dx.doi.org/urn:doi:10.1016/j.jneuroim.2022.577874reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 RYC-2010-06729Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2013-45178-PMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PEJ-2014-P-00015Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015-64123-PAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PGC2018-096003-B-I00open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2584392026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion |
| title |
Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion |
| spellingShingle |
Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion Heman-Bozadas, P. Parkinson's disease Microglia Macrophages Lipopolysaccharide Phagocytosis Dopamine Neurodegeneration Experimental models |
| title_short |
Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion |
| title_full |
Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion |
| title_fullStr |
Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion |
| title_full_unstemmed |
Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion |
| title_sort |
Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion |
| dc.creator.none.fl_str_mv |
Heman-Bozadas, P. Romero, Carolina Martínez-Remedios, P. Freitag, I. Frías, A. Saavedra-López, Elena|||0000-0001-9788-2414 Casanova, Paola|||0000-0002-4814-0577 Roig-Martínez, M. Cribaro, George Paul|||0000-0002-5251-1537 Rovirosa-Hernández, M. J. Hernandez-Baltazar, D. Barcia, Carlos|||0000-0003-0976-4245 |
| author |
Heman-Bozadas, P. |
| author_facet |
Heman-Bozadas, P. Romero, Carolina Martínez-Remedios, P. Freitag, I. Frías, A. Saavedra-López, Elena|||0000-0001-9788-2414 Casanova, Paola|||0000-0002-4814-0577 Roig-Martínez, M. Cribaro, George Paul|||0000-0002-5251-1537 Rovirosa-Hernández, M. J. Hernandez-Baltazar, D. Barcia, Carlos|||0000-0003-0976-4245 |
| author_role |
author |
| author2 |
Romero, Carolina Martínez-Remedios, P. Freitag, I. Frías, A. Saavedra-López, Elena|||0000-0001-9788-2414 Casanova, Paola|||0000-0002-4814-0577 Roig-Martínez, M. Cribaro, George Paul|||0000-0002-5251-1537 Rovirosa-Hernández, M. J. Hernandez-Baltazar, D. Barcia, Carlos|||0000-0003-0976-4245 |
| author2_role |
author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Parkinson's disease Microglia Macrophages Lipopolysaccharide Phagocytosis Dopamine Neurodegeneration Experimental models |
| topic |
Parkinson's disease Microglia Macrophages Lipopolysaccharide Phagocytosis Dopamine Neurodegeneration Experimental models |
| description |
Neuroinflammation contributes to neuronal degeneration in Parkinson's disease (PD). However, how brain inflammatory factors mediate the progression of neurodegeneration is still poorly understood. Experimental models of PD have shed light on the understanding of this phenomenon, but the exploration of inflammation-driven models is necessary to better characterize this aspect of the disorder. The use of lipopolysaccharide (LPS) to induce a neuroinflammation-mediated neuronal loss is useful to induce reliable elimination of dopaminergic neurons. Nevertheless, how this model parallels the PD-like neuroinflammation is uncertain. In the present work, we used the direct LPS injection as a model inductor to eliminate dopaminergic neurons of the substantia nigra pars compacta (SNpc) in rats and reevaluated the inflammatory reaction. High-resolution 3D histological examination revealed that, although LPS induced a reliable elimination of SNpc dopaminergic neurons, it also generated a massive inflammatory response. This inflammation-mediated injury was characterized by corralling, a damaged parenchyma occupied by a vast population of lesion-associated microglia and macrophages (LAMMs) undertaking wound compaction and scar formation, surrounded by highly reactive astrocytes. LAMMs tiled the entire lesion and engaged in long-standing phagocytic activity to resolve the injury. Additionally, modeling LPS inflammation in a cell culture system helped to understand the role of phagocytosis and cytotoxicity in the initial phases of dopaminergic degeneration and indicated that LAMM-mediated toxicity and phagocytosis coexist during LPS-mediated dopaminergic elimination. However, this type of severe inflammatory-mediated injury, and subsequent resolution appear to be different from the ageing-related PD scenario where the architectural structure of the parenchyma is mostly preserved. Thus, the necessity to explore new experimental models to properly mimic the inflammatory compound observed in PD degeneration. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2 2022-01-01 2022 2022-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
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https://ddd.uab.cat/record/258439 https://dx.doi.org/urn:doi:10.1016/j.jneuroim.2022.577874 |
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https://ddd.uab.cat/record/258439 https://dx.doi.org/urn:doi:10.1016/j.jneuroim.2022.577874 |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
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eng |
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Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 RYC-2010-06729 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2013-45178-P Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PEJ-2014-P-00015 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015-64123-P Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PGC2018-096003-B-I00 |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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