{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T06:50:47Z","timestamp":1794293447482,"version":"4.9.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Ministry of Science and Technology China Brain Initiative","award":["STI2030"],"award-info":[{"award-number":["STI2030"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071380"],"award-info":[{"award-number":["82071380"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873743"],"award-info":[{"award-number":["81873743"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271341"],"award-info":[{"award-number":["82271341"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Knowledge Innovation Program of Wuhan Shuguang Project"},{"name":"Tongji Hospital (HUST) Foundation for Excellent Young Scientists","award":["2020YQ06"],"award-info":[{"award-number":["2020YQ06"]}],"id":[{"id":"https:\/\/ror.org\/04xy45965","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Microglia-mediated neuroinflammation contributes to acute demyelination in neuromyelitis optica spectrum disorders (NMOSD). Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in the CSF has been associated with microglial activation in several neurodegenerative diseases. However, the basis for this immune-mediated attack and the pathophysiological role of sTREM2 in NMOSD remain to be elucidated.<\/jats:p>\n                  <jats:p>Here, we performed Mendelian randomization analysis and identified a genetic association between increased CSF sTREM2 and NMOSD risk. CSF sTREM2 was elevated in patients with NMOSD and was positively correlated with neural injury and other neuroinflammation markers. Single-cell RNA sequencing of human macrophage\/microglia-like cells in CSF, a proxy for microglia, showed that increased CSF sTREM2 was positively associated with microglial dysfunction in patients with NMOSD. Furthermore, we demonstrated that sTREM2 is a reliable biomarker of microglial activation in a mouse model of NMOSD. Using unbiased transcriptomic and lipidomic screens, we identified that excessive activation, overwhelmed phagocytosis of myelin debris, suppressed lipid metabolism and enhanced glycolysis underlie sTREM2-mediated microglial dysfunction, possibly through the nuclear factor kappa B (NF-\u03baB) signalling pathway.<\/jats:p>\n                  <jats:p>These molecular and cellular findings provide a mechanistic explanation for the genetic association between CSF sTREM2 and NMOSD risk and indicate that sTREM2 could be a potential biomarker of NMOSD progression and a therapeutic target for microglia-mediated neuroinflammation.<\/jats:p>","DOI":"10.1093\/brain\/awad321","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T08:21:56Z","timestamp":1695370916000},"page":"163-176","source":"Crossref","is-referenced-by-count":53,"title":["Soluble TREM2 triggers microglial dysfunction in neuromyelitis optica spectrum disorders"],"prefix":"10.1093","volume":"147","author":[{"given":"Chuan","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030 , China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology , Wuhan, 430030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030 , China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology , Wuhan, 430030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hao","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030 , China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology , Wuhan, 430030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030 , China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology , Wuhan, 430030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030 , China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology , Wuhan, 430030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Fan","family":"You","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030 , China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology , Wuhan, 430030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luo-Qi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030 , China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology , Wuhan, 430030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Hui","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030 , China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology , Wuhan, 430030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030 , China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology , Wuhan, 430030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Wei","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030 , China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology , Wuhan, 430030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-3380","authenticated-orcid":false,"given":"Long-Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, NY 14600, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai-Shi","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030 , China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology , Wuhan, 430030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9176-5150","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030 , China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology , Wuhan, 430030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"2024010419085855600_awad321-B1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1212\/WNL.0000000000011153","article-title":"Worldwide incidence and prevalence of neuromyelitis optica: A systematic 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