{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:59:57Z","timestamp":1785301197208,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neurocognitive impairment in obstructive sleep apnea (OSA) is primarily driven by intermittent hypoxia (IH)\u2010triggered neuroinflammation, where microglia play a pivotal role. The involvement of Olfml3 in IH\u2010induced neuroinflammation remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single\u2010cell RNA sequencing (scRNA\u2010seq) data from the hippocampi of IH\u2010induced OSA mice were analyzed to identify cell subpopulations, with further focus on Olfml3's differential expression, enriched pathways, and differentiation trajectories in microglia. An in\u00a0vitro OSA model was established using IH\u2010treated microglia. qRT\u2010PCR and western blot (WB) were utilized to assess Olfml3 and cytochrome b (Cybb) expression. Microglial polarization was evaluated via flow cytometry, while Enzyme\u2010Linked Immunosorbent Assay (ELISA) was applied to quantify inflammatory cytokines. Reactive oxygen species (ROS) were detected using fluorescent probes, and TLR4\/NF\u2010\u03baB pathway activation was verified by WB assessment of Toll\u2010like receptor 4 (TLR4), phosphorylated\u2010p65 (p\u2010p65), and p65 expression. Neuronal injury was assessed by treating neurons with microglial\u2010conditioned medium, followed by CCK\u20108 for viability assessment and flow cytometry for apoptosis analysis. An in\u00a0vivo OSA model was constructed by exposing mice to IH treatment. Cognitive deficits of mice were evaluated using the Morris water maze and blood oxygen saturation measurement, while pathological changes in brain tissue and cell apoptosis were examined via HE and TUNEL staining. Immunohistochemistry staining was employed to detect Olfml3 and Cybb protein levels. An immunofluorescence assay was conducted to measure Iba1 for evaluating microglial activation. ROS levels were detected by using fluorescent probes. The expression of TLR4\/NF\u2010\u03baB pathway proteins was assessed by WB. CD86\/CD206 ratios were analyzed by flow cytometry, and the expression of inflammatory cytokines was analyzed by ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>scRNA\u2010seq revealed reduced microglial proportions under hypoxia, with further analysis revealing that Olfml3 in microglia had a negative correlation with Cybb. An IH\u2010induced OSA model confirmed that Olfml3 overexpression alleviated microglial inflammation and neuronal injury by suppressing the TLR4\/NF\u2010\u03baB pathway via Cybb. In\u00a0vivo experiments further validated Olfml3's protective role against IH\u2010induced neuroinflammation in OSA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Olfml3 in microglia mitigates IH\u2010induced proinflammatory activation and neuronal injury via the Cybb\/TLR4\/NF\u2010\u03baB axis, thereby conferring neuroprotection against OSA\u2010associated neuroinflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71006","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:11:14Z","timestamp":1783527074000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Olfml3 Regulates Microglial Inflammation and Neuronal Injury in Obstructive Sleep Apnea via Cybb\u2010Mediated\n                    <scp>TLR4<\/scp>\n                    \/\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Pathway"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8852-9018","authenticated-orcid":false,"given":"Deqiu","family":"Kong","sequence":"first","affiliation":[{"name":"Otorhinolaryngology\u2010Head and Neck Surgery The First Affiliated Hospital of Ningbo University  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaowen","family":"Wang","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology\u2010Head and Neck Surgery The First Affiliated Hospital of Ningbo University  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology\u2010Head and Neck Surgery The First Affiliated Hospital of Ningbo University  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cihao","family":"Hu","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology\u2010Head and Neck Surgery The First Affiliated Hospital of Ningbo University  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology\u2010Head and Neck Surgery The First Affiliated Hospital of Ningbo University  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Chen","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology\u2010Head and Neck Surgery The First Affiliated Hospital of Ningbo University  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe2407117"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI137560"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23663"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23168924"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-020-03168-y"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17682"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-020-08627-x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01048-w"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03777-y"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1538-9"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00553"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13086"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-21-0559"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000000309"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2024.578411"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000751RR"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01521-1"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01522-0"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jenvman.2024.122948"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-02014-w"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-023-03931-x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/5855889"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2023100"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.76451"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01728"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00856-y"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-024-00591-0"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2023.102459"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113522"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031205"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-019-02931-0"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112849"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-024-09995-4"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2024.07.013"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1343842"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.71006","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns.71006","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.71006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:14:05Z","timestamp":1785298445000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns.71006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":35,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/cns.71006"],"URL":"https:\/\/doi.org\/10.1002\/cns.71006","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2025-10-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71006"}}