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| Página principal > Artículos > Artículos publicados > Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion |
(Universitat Autònoma de Barcelona. Institut de Neurociències) (Universitat Autònoma de Barcelona. Institut de Neurociències) (Universitat Autònoma de Barcelona. Institut de Neurociències) (Universitat Autònoma de Barcelona. Institut de Neurociències)
| Fecha: | 2022 |
| Resumen: | 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. |
| Ayudas: | Ministerio de Ciencia e Innovación RYC-2010-06729 Ministerio de Economía y Competitividad SAF2013-45178-P Ministerio de Economía y Competitividad PEJ-2014-P-00015 Ministerio de Economía y Competitividad SAF2015-64123-P Agencia Estatal de Investigación PGC2018-096003-B-I00 |
| Nota: | Altres ajuts: acords transformatius de la UAB |
| Derechos: | Aquest 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.  |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió publicada |
| Materia: | Parkinson's disease ; Microglia ; Macrophages ; Lipopolysaccharide ; Phagocytosis ; Dopamine ; Neurodegeneration ; Experimental models |
| Publicado en: | Journal of Neuroimmunology, Vol. 367 (2022) , ISSN 1872-8421 |
