{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:08:11Z","timestamp":1791472091531,"version":"4.3.4"},"reference-count":71,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFC0861000"],"award-info":[{"award-number":["2020YFC0861000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFC0841300"],"award-info":[{"award-number":["2020YFC0841300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801318"],"award-info":[{"award-number":["81801318"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that leads to severe disability. A large proportion of NMOSD patients are seropositive for aquaporin\u20104 autoantibodies (AQP4\u2010IgG, named as NMO\u2010IgG) targeting AQP4, which is selectively expressed on astrocytes in the central nervous system. This study tests the hypothesis that in response to NMO\u2010IgG, the pathogenic astrocyte\u2010derived exosomes are released and injure the neighboring cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IgG purified from serum of either NMOSD patients or healthy controls was used to generate astrocyte\u2010derived exosomes (AST\u2010Exos<jats:sup>NMO<\/jats:sup> vs AST\u2010Exos<jats:sup>CON<\/jats:sup>) in cultured rat astrocytes. The exosomes were respectively delivered to cultured rat oligodendrocytes in vitro, tissue culture of rat optic nerve ex vivo, and rat optic nerve in vivo to evaluate the pathogenic roles of AST\u2010Exos<jats:sup>NMO<\/jats:sup>. The microRNA (miRNA) sequencing of AST\u2010Exos and verification were performed to identify the key pathogenic miRNA. The custom\u2010designed adeno\u2010associated virus (AAV) antagonizing the key miRNA was evaluated for its therapeutic effects in vivo. Moreover, the serum levels of the key exosomal miRNA were measured between NMOSD patients and healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AST\u2010Exos<jats:sup>NMO<\/jats:sup> led to notable demyelination in both cultured oligodendrocytes and optic nerve tissue. Exosomal miR\u2010129\u20102\u20103p was identified as the key miRNA mediating the demyelinating pathogenesis via downstream target gene <jats:italic>SMAD3<\/jats:italic>. AAV antagonizing miR\u2010129\u20102\u20103p protected against demyelination in an NMOSD rodent model. The serum exosomal miR\u2010129\u20102\u20103p level was significantly elevated in NMOSD patients and correlated with disease severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Astrocytes targeted by NMO\u2010IgG release pathogenic exosomes that could potentially be used as therapeutic targets or disease monitoring biomarkers in NMOSD. ANN NEUROL 2023;94:163\u2013181<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.26650","type":"journal-article","created":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T16:15:52Z","timestamp":1679847352000},"page":"163-181","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Astrocyte\u2010Derived Exosomes Contribute to Pathologies of Neuromyelitis Optica Spectrum Disorder in Rodent Model"],"prefix":"10.1002","volume":"94","author":[{"given":"Yi","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7974-9051","authenticated-orcid":false,"given":"Bo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology First Affiliated Hospital of University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangyang No. 1 People's Hospital Hubei University of Medicine  Xiangyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiyue","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjie","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bitao","family":"Bu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dapeng","family":"Mou","sequence":"additional","affiliation":[{"name":"Beijing Tongren Eye Center, Beijing Tongren Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenju","family":"Yi","sequence":"additional","affiliation":[{"name":"Research Center Seventh Affiliated Hospital of Sun Yat\u2010sen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5589-3668","authenticated-orcid":false,"given":"Fengfei","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College Fudan University  Shanghai 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 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-16"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(07)70216-8"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00888"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.01.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2020.577387"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm062"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050304"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.72"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.11.003"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab102"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2020.1732927"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.344325"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1128-3"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1172-z"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci67554"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf151"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri855"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471143030.cb0322s30"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.S272378"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1054-4"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.06.029"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060308-103103"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000488365"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13036-019-0193-0"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2484"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2017.02.045"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3791\/3814"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2005.tb00053.x"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1159\/000111276"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci70577"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22551"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp309"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01874-6"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0403-8"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118217"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2014.02.011"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22635"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2018.12.002"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2016.11.008"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2013.12.010"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1596"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.08.035"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2018.06.017"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12271"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq177"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12211"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa227"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2019.06.019"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01761-0"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.04.017"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207450903428970"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1212\/nxi.0000000000000841"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017385108"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23621"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072919"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12099"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci134816"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02576"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.21945"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.00380-20"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2195"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102221"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-09699-2"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513515085"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-019-0143-2"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2016.09.011"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-021-00938-6"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa898"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12793"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.12.015"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-5-22"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.26650","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T01:54:47Z","timestamp":1692496487000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.26650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,11]]},"references-count":71,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/ana.26650"],"URL":"https:\/\/doi.org\/10.1002\/ana.26650","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,11]]},"assertion":[{"value":"2022-09-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}