{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:56:33Z","timestamp":1787237793340,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T00:00:00Z","timestamp":1625616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["RO1 NS100839"],"award-info":[{"award-number":["RO1 NS100839"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["19CDA34490003"],"award-info":[{"award-number":["19CDA34490003"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Gangliosides, the major sialic\u2010acid containing glycosphingolipids in the mammalian brain, play important roles in brain development and neural functions. Here, we show that the b\u2010series ganglioside GD3 and its biosynthetic enzyme, GD3\u2010synthase (GD3S), were up\u2010regulated predominantly in the microglia of mouse hippocampus from 2 to 7\u00a0days following global cerebral ischemia (GCI). Interestingly, GD3S knockout (GD3S\u2010KO) mice exhibited decreased hippocampal neuronal loss following GCI, as compared to wild\u2010type (WT) mice. While comparable levels of astrogliosis and microglial proliferation were observed between WT and GD3S\u2010KO mice, the phagocytic capacity of the GD3S\u2010KO microglia was significantly compromised after GCI. At 2 and 4\u00a0days following GCI, the GD3S\u2010KO microglia demonstrated decreased amoebic morphology, reduced neuronal material engulfment, and lower expression of the phagolysosome marker CD68, as compared to the WT microglia. Finally, by using a microglia\u2010primary neuron co\u2010culture model, we demonstrated that the GD3S\u2010KO microglia isolated from mouse brains at 2\u00a0days after GCI are less neurotoxic to co\u2010cultured hippocampal neurons than the WT\u2010GCI microglia. Moreover, the percentage of microglia with engulfed neuronal elements in the co\u2010cultured wells was also significantly decreased in the GD3S\u2010KO mice after GCI. Interestingly, the impaired phagocytic capacity of GD3S\u2010KO microglia could be partially restored by pre\u2010treatment with exogenous ganglioside GD3. Altogether, this study provides functional evidence that ganglioside GD3 regulates phagocytosis by microglia in an ischemic stroke model. Our data also suggest that the GD3\u2010linked microglial phagocytosis may contribute to the mechanism of delayed neuronal death following ischemic brain injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15455-fig-0009-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jnc.15455","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T14:28:11Z","timestamp":1623853691000},"page":"737-752","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Ganglioside GD3 is up\u2010regulated in microglia and regulates phagocytosis following global cerebral ischemia"],"prefix":"10.1111","volume":"158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0649-135X","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Regenerative Medicine Medical College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6499-7952","authenticated-orcid":false,"given":"Quanguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Regenerative Medicine Medical College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Medical College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Regenerative Medicine Medical College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan M.","family":"Dhandapani","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Medical College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrell W.","family":"Brann","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Regenerative Medicine Medical College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7873-195X","authenticated-orcid":false,"given":"Robert K.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Regenerative Medicine Medical College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.26.8.1478"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1914742117"},{"key":"e_1_2_10_4_1","first-page":"229","article-title":"Alterations in brain gangliosides and other lipids of patients with Creutzfeldt\u2010Jakob disease and subacute sclerosing panencephalitis (SSPE)","volume":"54","author":"Ando S.","year":"1984","journal-title":"The Japanese Journal of Experimental Medicine"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.188"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb8587"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2012.05.002"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3710"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15327"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0130364"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-55885-2"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401834"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600495"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.05.003"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-013-8620-6"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1194637"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(84)80017-X"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199604)16:4<291::AID-GLIA1>3.0.CO;2-3"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00304636"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1516-2"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90027-2"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-0186(92)90058-Y"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(96)10049-7"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2009.06.001"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0115-20.2020"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(02)00339-6"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-004-1473-5"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1308679110"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn109"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04910.x"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-02-01001.1995"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00471-9"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490360407"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.99-1028com"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01782-9"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2005.08.004"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401027"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00993269"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15137"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3702"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2275-14.2014"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.09.017"},{"key":"e_1_2_10_43_1","article-title":"Astrocyte\u2010derived estrogen regulates reactive astrogliosis and is neuroprotective following ischemic brain injury","author":"Wang J.","year":"2020","journal-title":"The Journal of Neuroscience: The Official Journal of the Society for"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0888-20.2020"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1307224110"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.2217\/fnl.10.1"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.440130103"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/cn300216h"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000096063.84070.C1"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R300020-JLR200"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1974.tb06931.x"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.5650\/jos.60.537"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1136\/svn-2018-000196"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15455","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jnc.15455","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.15455","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T18:49:54Z","timestamp":1692989394000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.15455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,7]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1111\/jnc.15455"],"URL":"https:\/\/doi.org\/10.1111\/jnc.15455","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,7]]},"assertion":[{"value":"2021-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}