{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T06:53:17Z","timestamp":1747205597191,"version":"3.40.5"},"posted":{"date-parts":[[2021,8,2]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"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":[[2021,7,23]]},"abstract":"<title>Abstract<\/title>\n        <p><bold>Background <\/bold>Microglia, the \u2018resident immunocompetent cells\u2019 of the central nervous system (CNS), are key players in innate immunity, synaptic refinement and homeostasis. Dysfunctional microglia contribute heavily to the creation of a toxic inflammatory milieu, a driving factor in the pathophysiology of several CNS disorders. Strategies for modulation of microglial function are required to tackle exacerbated tissue inflammation. Carbon monoxide (CO) is an endogenous gaseous molecule, produced by the degradation of haem, which presents several biological functions, namely anti-inflammatory, anti-apoptotic, pro-homeostatic and cytoprotective.<bold>Methods <\/bold>A novel molybdenum based CO-releasing molecule ALF826 was used for the assessment of neuron-microglia remote communication. Primary cultures of rat microglia and neurons, or BV-2 microglial mouse cell line and CAD neuronal mouse cell line were used to study microglia to neuron interaction. An approach based on microglial derived conditioned media in neuronal culture was applied.<bold>Results<\/bold> Medium derived from CO-treated microglia provided indirect neuroprotection against inflammation by limiting lipopolysaccharide (LPS)-induced expression of reactivity markers (CD11b), production of reactive oxygen species (ROS) and secretion of inflammatory factors (TNF-\u03b1, 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, microglial medium also prevented neuronal cell death induced by pro-oxidant <italic>tert<\/italic>-Butyl hydroperoxide (<italic>t<\/italic>-BHP). ALF826 treatment reinforced microglia secretion of Interleukin-10 (IL-10) and adenosine, mediators which may be involved in providing protection against <italic>t<\/italic>-BHP stress in this remote communication model. Chemical inhibition of adenosine receptors A<sub>2A<\/sub> and A<sub>1<\/sub> reverted CO-derived neuroprotective effect, further highlighting a role for CO in regulating neuron-microglia communication <italic>via<\/italic> purinergic signalling.<bold>Conclusions <\/bold>Our findings indicate that CO has a modulatory role on microglia-to-neuron communication, promoting neuroprotection in a non-cell autonomous manner. In conclusion, CO-induced neuroprotection is afforded (i) by blocking exacerbated microglial inflammation and (ii) by the microglial release of neurotrophic factors. For the first time it is described CO improvement of microglial neurotrophism under non-inflammatory conditions.<\/p>","DOI":"10.21203\/rs.3.rs-745011\/v1","type":"posted-content","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T21:22:25Z","timestamp":1627939345000},"source":"Crossref","is-referenced-by-count":1,"title":["Carbon Monoxide Modulation of Microglia-Neuron Communication: Anti-Neuroinflammatory and Neurotrophic Role"],"prefix":"10.21203","author":[{"given":"Nuno L.","family":"Soares","sequence":"first","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa"}]},{"given":"In\u00eas","family":"Paiva","sequence":"additional","affiliation":[{"name":"NOVA School of Science and Technology, Universidade Nova de Lisboa"}]},{"given":"Joana","family":"Bravo","sequence":"additional","affiliation":[{"name":"I3S: Universidade do Porto Instituto de Investigacao e Inovacao em Saude"}]},{"given":"Claudia S.F.","family":"Queiroga","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa"}]},{"given":"Bernadete F.","family":"Melo","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa"}]},{"given":"Silvia V.","family":"Conde","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Universidade Nova de Lisboa"}]},{"given":"Carlos C.","family":"Rom\u00e3o","sequence":"additional","affiliation":[{"name":"ITQB: Universidade Nova de Lisboa Instituto de Tecnologia Quimica e Biologica"}]},{"given":"Teresa","family":"Summavielle","sequence":"additional","affiliation":[{"name":"I3S: Universidade do Porto Instituto de Investigacao e Inovacao em Saude"}]},{"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"}]}],"member":"297","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-745011\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-745011\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T03:21:12Z","timestamp":1659064872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-745011\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,2]]},"references-count":0,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-745011\/v1","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1007\/s12035-021-02643-z","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2021,8,2]]},"subtype":"preprint"}}