Carbon Monoxide Modulation of Microglia-Neuron Communication
| Autor(a) principal: | |
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| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/131255 |
Resumo: | This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia/Ministério da Ciência (FCT), Tecnologia e Ensino Superior in the framework of FCT-ANR/NEU-NMC/0022/2012 grant, PTDC/MEC-NEU/28750/2017 grant, Applied Molecular Biosciences Unit-UCIBIO (UID/Multi/04378/2019) grant; LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy; and FCT provided individual financial support to NLS (PD/BD/127819/2016), BFM (PD/BD/128336/2017) and HLAV (IF/00185/2012). |
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Carbon Monoxide Modulation of Microglia-Neuron CommunicationAnti-Neuroinflammatory and Neurotrophic RoleCarbon monoxideMicrogliaNeuroinflammationNeuronsNeurotrophismNeurologyCellular and Molecular NeuroscienceThis work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia/Ministério da Ciência (FCT), Tecnologia e Ensino Superior in the framework of FCT-ANR/NEU-NMC/0022/2012 grant, PTDC/MEC-NEU/28750/2017 grant, Applied Molecular Biosciences Unit-UCIBIO (UID/Multi/04378/2019) grant; LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy; and FCT provided individual financial support to NLS (PD/BD/127819/2016), BFM (PD/BD/128336/2017) and HLAV (IF/00185/2012).Microglia, the ‘resident immunocompetent cells’ of the central nervous system (CNS), are key players in innate immunity, synaptic refinement and homeostasis. Dysfunctional microglia contribute heavily to creating a toxic inflammatory milieu, a driving factor in the pathophysiology of several CNS disorders. Therefore, strategies to modulate the microglial function are required to tackle exacerbated tissue inflammation. Carbon monoxide (CO), an endogenous gaseous molecule produced by the degradation of haem, has anti-inflammatory, anti-apoptotic, and pro-homeostatic and cytoprotective roles, among others. ALF-826A, a novel molybdenum-based CO-releasing molecule, was used for the assessment of neuron-microglia remote communication. Primary cultures of rat microglia and neurons, or the BV-2 microglial and CAD neuronal murine cell lines, were used to study the microglia-neuron interaction. An approach based on microglial-derived conditioned media in neuronal culture was applied. Medium derived from CO-treated microglia provided indirect neuroprotection against inflammation by limiting the lipopolysaccharide (LPS)-induced expression of reactivity markers (CD11b), the production of reactive oxygen species (ROS) and the secretion of inflammatory factors (TNF-α, nitrites). This consequently prevented neuronal cell death and maintained neuronal morphology. In contrast, in the absence of inflammatory stimulus, conditioned media from CO-treated microglia improved neuronal morphological complexity, which is an indirect manner of assessing neuronal function. Likewise, the microglial medium also prevented neuronal cell death induced by pro-oxidant tert-Butyl hydroperoxide (t-BHP). ALF-826 treatment reinforced microglia secretion of Interleukin-10 (IL-10) and adenosine, mediators that may protect against t-BHP stress in this remote communication model. Chemical inhibition of the adenosine receptors A2A and A1 reverted the CO-derived neuroprotective effect, further highlighting a role for CO in regulating neuron-microglia communication via purinergic signalling. Our findings indicate that CO has a modulatory role on microglia-to-neuron communication, promoting neuroprotection in a non-cell autonomous manner. CO enhances the microglial release of neurotrophic factors and blocks exacerbated microglial inflammation. CO improvement of microglial neurotrophism under non-inflammatory conditions is here described for the first time.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)UCIBIO - Applied Molecular Biosciences UnitDQ - Departamento de QuímicaInstituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNSoares, Nuno L.Paiva, InêsBravo, JoanaQueiroga, Cláudia S. F.Melo, Bernadete F.Conde, Sílvia V.Romão, Carlos C.Summavielle, TeresaVieira, Helena L. A.2022-01-21T00:21:36Z2022-022022-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/131255eng0893-7648PURE: 35038955https://doi.org/10.1007/s12035-021-02643-zinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:09:48Zoai:run.unl.pt:10362/131255Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:47:01.450706Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Carbon Monoxide Modulation of Microglia-Neuron Communication Anti-Neuroinflammatory and Neurotrophic Role |
| title |
Carbon Monoxide Modulation of Microglia-Neuron Communication |
| spellingShingle |
Carbon Monoxide Modulation of Microglia-Neuron Communication Soares, Nuno L. Carbon monoxide Microglia Neuroinflammation Neurons Neurotrophism Neurology Cellular and Molecular Neuroscience |
| title_short |
Carbon Monoxide Modulation of Microglia-Neuron Communication |
| title_full |
Carbon Monoxide Modulation of Microglia-Neuron Communication |
| title_fullStr |
Carbon Monoxide Modulation of Microglia-Neuron Communication |
| title_full_unstemmed |
Carbon Monoxide Modulation of Microglia-Neuron Communication |
| title_sort |
Carbon Monoxide Modulation of Microglia-Neuron Communication |
| author |
Soares, Nuno L. |
| author_facet |
Soares, Nuno L. Paiva, Inês Bravo, Joana Queiroga, Cláudia S. F. Melo, Bernadete F. Conde, Sílvia V. Romão, Carlos C. Summavielle, Teresa Vieira, Helena L. A. |
| author_role |
author |
| author2 |
Paiva, Inês Bravo, Joana Queiroga, Cláudia S. F. Melo, Bernadete F. Conde, Sílvia V. Romão, Carlos C. Summavielle, Teresa Vieira, Helena L. A. |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) UCIBIO - Applied Molecular Biosciences Unit DQ - Departamento de Química Instituto de Tecnologia Química e Biológica António Xavier (ITQB) RUN |
| dc.contributor.author.fl_str_mv |
Soares, Nuno L. Paiva, Inês Bravo, Joana Queiroga, Cláudia S. F. Melo, Bernadete F. Conde, Sílvia V. Romão, Carlos C. Summavielle, Teresa Vieira, Helena L. A. |
| dc.subject.por.fl_str_mv |
Carbon monoxide Microglia Neuroinflammation Neurons Neurotrophism Neurology Cellular and Molecular Neuroscience |
| topic |
Carbon monoxide Microglia Neuroinflammation Neurons Neurotrophism Neurology Cellular and Molecular Neuroscience |
| description |
This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia/Ministério da Ciência (FCT), Tecnologia e Ensino Superior in the framework of FCT-ANR/NEU-NMC/0022/2012 grant, PTDC/MEC-NEU/28750/2017 grant, Applied Molecular Biosciences Unit-UCIBIO (UID/Multi/04378/2019) grant; LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy; and FCT provided individual financial support to NLS (PD/BD/127819/2016), BFM (PD/BD/128336/2017) and HLAV (IF/00185/2012). |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-01-21T00:21:36Z 2022-02 2022-02-01T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10362/131255 |
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http://hdl.handle.net/10362/131255 |
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eng |
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eng |
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0893-7648 PURE: 35038955 https://doi.org/10.1007/s12035-021-02643-z |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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