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https://hdl.handle.net/10316/115072
Título: | Neuronal control of microglia through the mitochondria | Autor: | Pereira-Santos, A. R. Candeias, Emanuel Magalhães, J. D. Empadinhas, Nuno Esteves, A. Raquel Cardoso, Sandra Morais |
Palavras-chave: | Neurons; Microglia; β-N-methylamino-L-alanine; Mitochondrial dysfunction; Neuronal innate immunity | Data: | 16-Abr-2024 | Editora: | Elsevier | Projeto: | UIBD/NEU/04539/2020 UIDB/04539/2020 UIDP/04539/2020 LA/P/0058/2020 |
Título da revista, periódico, livro ou evento: | Biochimica et Biophysica Acta - Molecular Basis of Disease | Volume: | 1870 | Número: | 5 | Resumo: | The microbial toxin β-N-methylamino-L-alanine (BMAA), which is derived from cyanobacteria, targets neuronal mitochondria, leading to the activation of neuronal innate immunity and, consequently, neurodegeneration. Although known to modulate brain inflammation, the precise role of aberrant microglial function in the neurodegenerative process remains elusive. To determine if neurons signal microglial cells, we treated primary cortical neurons with BMAA and then co-cultured them with the N9 microglial cell line. Our observations indicate that microglial cell activation requires initial neuronal priming. Contrary to what was observed in cortical neurons, BMAA was not able to activate inflammatory pathways in N9 cells. We observed that microglial activation is dependent on mitochondrial dysfunction signaled by BMAA-treated neurons. In this scenario, the NLRP3 pro-inflammatory pathway is activated due to mitochondrial impairment in N9 cells. These results demonstrate that microglia activation in the presence of BMAA is dependent on neuronal signaling. This study provides evidence that neurons may trigger microglia activation and subsequent neuroinflammation. In addition, we demonstrate that microglial activation may have a protective role in ameliorating neuronal innate immune activation, at least in the initial phase. This work challenges the current understanding of neuroinflammation by assigning the primary role to neurons. | URI: | https://hdl.handle.net/10316/115072 | ISSN: | 09254439 | DOI: | 10.1016/j.bbadis.2024.167167 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais FMUC Medicina - Artigos em Revistas Internacionais |
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Ficheiro | Descrição | Tamanho | Formato | |
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Neuronal control of microglia through the mitochondria.pdf | 7.51 MB | Adobe PDF | Ver/Abrir |
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