{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T06:54:07Z","timestamp":1747205647696,"version":"3.40.5"},"posted":{"date-parts":[[2021,8,31]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,8,28]]},"abstract":"<title>Abstract<\/title>\n        <p>Microglia are the immune competent cell of the central nervous system (CNS), promoting brain homeostasis and regulating inflammatory response against infection and injury. Chronic or exacerbated neuroinflammation is a cause of damage in several brain pathologies. Endogenous carbon monoxide (CO), produced from the degradation of heme, is described as anti-apoptotic and anti-inflammatory in several contexts, including in the CNS. Neuroglobin (Ngb) is a haemoglobin-homologous protein, which upregulation triggers antioxidant defence and prevents neuronal apoptosis. Thus, we hypothesized a crosstalk between CO and Ngb, in particular, that the anti-neuroinflammatory role of CO in microglia  depends on Ngb. A novel CO-releasing molecule (ALF826) based on molybdenum was used for delivering CO in microglial culture.BV-2 mouse microglial cell line was challenged with lipopolysaccharide (LPS) for triggering inflammation, and after 6h ALF826 was added. CO exposure limited inflammation by decreasing inducible nitric oxide synthase (iNOS) expression and the production of nitric oxide (NO) and tumour necrosis factor-a  (TNF-a), and by increasing interleukine-10 (IL-10) release. CO-induced Ngb upregulation correlated in time with CO\u2019s anti-inflammatory effect. Moreover, knocking down Ngb reversed the anti-inflammatory effect of CO, suggesting that dependents on Ngb expression. CO-induced Ngb upregulation was independent on ROS signalling, but partially dependent on the transcriptional factor SP1. Finally, microglial cell metabolism is also involved in the inflammatory response. In fact, LPS treatment decreased oxygen consumption in microglia, indicating a switch to glycolysis, which is associated with a proinflammatory. While CO treatment increased oxygen consumption, reverting LPS effect and indicating a metabolic shift into a more oxidative metabolism. Moreover, in the absence of Ngb this phenotype was no longer observed, indicating Ngb is needed for CO\u2019s modulation of microglial metabolism. Finally, the metabolic shift induced by CO did not depend on alteration of mitochondrial population. In conclusion, neuroglobin emerges for the first time as a key player for CO signalling against exacerbated neuroinflammation in microglia.<\/p>","DOI":"10.21203\/rs.3.rs-852619\/v1","type":"posted-content","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T22:06:32Z","timestamp":1630447592000},"source":"Crossref","is-referenced-by-count":0,"title":["Carbon Monoxide-Neuroglobin Axis Targeting Metabolism Against Neuroinflammation"],"prefix":"10.21203","author":[{"given":"Daniela","family":"Dias-Pedroso","sequence":"first","affiliation":[{"name":"NOVA medical School, Universidade Nova de Lisboa"}]},{"given":"Jos\u00e9 S.","family":"Ramalho","sequence":"additional","affiliation":[{"name":"NOVA Medical School, Universidade Nova de Lisboa"}]},{"given":"Vilma A.","family":"Sard\u00e3o","sequence":"additional","affiliation":[{"name":"CNC CIBB Universidade de Coimbra"}]},{"given":"John G.","family":"Jones","sequence":"additional","affiliation":[{"name":"CNC CIBB Universidade de Coimbra"}]},{"given":"Carlos C.","family":"Rom\u00e3o","sequence":"additional","affiliation":[{"name":"Universidade Nova de Lisboa Instituto de Tecnologia Quimica e Biologica"}]},{"given":"Paulo J.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"CNC CIBB Universidade de Coimbra"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9415-3742","authenticated-orcid":false,"given":"Helena L.A.","family":"Vieira","sequence":"additional","affiliation":[{"name":"NOVA School of Science and Technology, Universidade Nova de Lisboa"}]}],"member":"297","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-852619\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-852619\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T22:06:42Z","timestamp":1630447602000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-852619\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":0,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-852619\/v1","relation":{},"subject":[],"published":{"date-parts":[[2021,8,31]]},"subtype":"preprint"}}