{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:44:11Z","timestamp":1792507451241,"version":"4.5.0"},"reference-count":72,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"21","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,5,26]]},"abstract":"<jats:p>Sepsis-associated encephalopathy (SAE) is a severe and frequent complication of sepsis causing delirium, coma, and long-term cognitive dysfunction. We identified microglia and C1q complement activation in hippocampal autopsy tissue of patients with sepsis and increased C1q-mediated synaptic pruning in a murine polymicrobial sepsis model. Unbiased transcriptomics of hippocampal tissue and isolated microglia derived from septic mice revealed an involvement of the innate immune system, complement activation, and up-regulation of lysosomal pathways during SAE in parallel to neuronal and synaptic damage. Microglial engulfment of C1q-tagged synapses could be prevented by stereotactic intrahippocampal injection of a specific C1q-blocking antibody. Pharmacologically targeting microglia by PLX5622, a CSF1-R inhibitor, reduced C1q levels and the number of C1q-tagged synapses, protected from neuronal damage and synapse loss, and improved neurocognitive outcome. Thus, we identified complement-dependent synaptic pruning by microglia as a crucial pathomechanism for the development of neuronal defects during SAE.<\/jats:p>","DOI":"10.1126\/sciadv.abq7806","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T13:58:21Z","timestamp":1685109501000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":161,"title":["Microglia mediate neurocognitive deficits by eliminating C1q-tagged synapses in sepsis-associated encephalopathy"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6529-9176","authenticated-orcid":true,"given":"Ha-Yeun","family":"Chung","sequence":"first","affiliation":[{"name":"Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena 07747, Germany."},{"name":"Center for Sepsis Control and Care, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5854-3759","authenticated-orcid":true,"given":"Jonathan","family":"Wickel","sequence":"additional","affiliation":[{"name":"Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena 07747, Germany."},{"name":"Center for Sepsis Control and Care, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3085-9740","authenticated-orcid":true,"given":"Nina","family":"Hahn","sequence":"additional","affiliation":[{"name":"Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena 07747, Germany."},{"name":"Center for Sepsis Control and Care, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9552-2001","authenticated-orcid":true,"given":"Nils","family":"Mein","sequence":"additional","affiliation":[{"name":"Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8131-3224","authenticated-orcid":true,"given":"Meike","family":"Schwarzbrunn","sequence":"additional","affiliation":[{"name":"Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2825-7943","authenticated-orcid":true,"given":"Philipp","family":"Koch","sequence":"additional","affiliation":[{"name":"Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena 07745, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9627-3991","authenticated-orcid":true,"given":"Mihai","family":"Ceanga","sequence":"additional","affiliation":[{"name":"Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2050-4655","authenticated-orcid":true,"given":"Holger","family":"Haselmann","sequence":"additional","affiliation":[{"name":"Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3098-5961","authenticated-orcid":true,"given":"Carolin","family":"Baade-B\u00fcttner","sequence":"additional","affiliation":[{"name":"Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4003-5809","authenticated-orcid":true,"given":"Nikolai","family":"von Stackelberg","sequence":"additional","affiliation":[{"name":"Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3180-5318","authenticated-orcid":true,"given":"Nina","family":"Hempel","sequence":"additional","affiliation":[{"name":"Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6546-8245","authenticated-orcid":true,"given":"Lars","family":"Schmidl","sequence":"additional","affiliation":[{"name":"Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9199-8990","authenticated-orcid":true,"given":"Marco","family":"Groth","sequence":"additional","affiliation":[{"name":"Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena 07745, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4591-7037","authenticated-orcid":true,"given":"Nico","family":"Andreas","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Jena University Hospital, Jena 07743, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9584-7958","authenticated-orcid":true,"given":"Juliane","family":"G\u00f6tze","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Jena 07747, Germany."},{"name":"Septomics Research Center, Jena University Hospital, Jena 07745, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7130-0006","authenticated-orcid":true,"given":"Sina M.","family":"Coldewey","sequence":"additional","affiliation":[{"name":"Center for Sepsis Control and Care, Jena University Hospital, Jena 07747, Germany."},{"name":"Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Jena 07747, Germany."},{"name":"Septomics Research Center, Jena University Hospital, Jena 07745, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1521-3514","authenticated-orcid":true,"given":"Michael","family":"Bauer","sequence":"additional","affiliation":[{"name":"Center for Sepsis Control and Care, Jena University Hospital, Jena 07747, Germany."},{"name":"Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6677-3124","authenticated-orcid":true,"given":"Christian","family":"Mawrin","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, University of Magdeburg, Magdeburg, Germany."},{"name":"Section of Pathology, Institute of Forensic Medicine, Jena University Hospital, Jena 07749, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4114-3748","authenticated-orcid":true,"given":"Justina","family":"Dargvainiene","sequence":"additional","affiliation":[{"name":"Neuroimmunology, Institute of Clinical Chemistry, UKSH, Kiel\/L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8972-515X","authenticated-orcid":true,"given":"Frank","family":"Leypoldt","sequence":"additional","affiliation":[{"name":"Neuroimmunology, Institute of Clinical Chemistry, UKSH, Kiel\/L\u00fcbeck, Germany."},{"name":"Department of Neurology, Christian-Albrechts University, Kiel 24105, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-954X","authenticated-orcid":true,"given":"Stephan","family":"Steinke","sequence":"additional","affiliation":[{"name":"Department Medical Biotechnology, Institute of Biochemistry, Biotechnology and Bioinformatics, Technische Universit\u00e4t Braunschweig, Braunschweig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8336-3485","authenticated-orcid":true,"given":"Zhao-Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena 07745, Germany."},{"name":"Faculty of Biological Sciences, Friedrich Schiller University, Jena 07745, Germany."},{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3418-6045","authenticated-orcid":true,"given":"Michael","family":"Hust","sequence":"additional","affiliation":[{"name":"Department Medical Biotechnology, Institute of Biochemistry, Biotechnology and Bioinformatics, Technische Universit\u00e4t Braunschweig, Braunschweig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9859-581X","authenticated-orcid":true,"given":"Christian","family":"Geis","sequence":"additional","affiliation":[{"name":"Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena 07747, Germany."},{"name":"Center for Sepsis Control and Care, Jena University Hospital, Jena 07747, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201504-0781OC"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9030703"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-017-4807-z"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.183"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-302883"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.1553"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-019-0158-7"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2016.12.015"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900317"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aag2590"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110647"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.11.030"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-112618-043515"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4397"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1202529"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.11.013"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz2288"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.10.014"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1722613115"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020105380"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.040"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11674-z"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2402-19.2020"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-4-4"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031814"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3554"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00620-5"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.09.018"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201846171"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2011.05.019"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-320106"},{"key":"e_1_3_3_33_2","doi-asserted-by":"crossref","first-page":"e0211184","DOI":"10.1371\/journal.pone.0211184","article-title":"The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy\u2014A prospective, pilot observational study","volume":"14","author":"Ehler J.","year":"2019","unstructured":"J.\u00a0Ehler, A.\u00a0Petzold, M.\u00a0Wittstock, S.\u00a0Kolbaske, M.\u00a0Gloger, J.\u00a0Henschel, A.\u00a0Heslegrave, H.\u00a0Zetterberg, M. P.\u00a0Lunn, P. S.\u00a0Rommer, A.\u00a0Grossmann, T.\u00a0Sharshar, G.\u00a0Richter, G.\u00a0Noldge-Schomburg, M.\u00a0Sauer, The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy\u2014A prospective, pilot observational study. PLOS ONE 14, e0211184 (2019).","journal-title":"PLOS ONE"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0814-9"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj2685"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0403-7"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018101064"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15491"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24398"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2003.09.004"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad8373"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-012-8354-x"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00643-7"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5002-13.2014"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12502"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922788117"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.07.001"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9658-2_16"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02367-w"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.965305"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03892-7"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.12.019"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-036527"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_3_3_55_2","doi-asserted-by":"crossref","unstructured":"B. Gr\u00fcnewald J.\u00a0Wickel N.\u00a0Hahn F.\u00a0H\u00f6rhold H.\u00a0Rupp H.-Y. Chung H.\u00a0Haselmann A.\u00a0S.\u00a0Strauss L.\u00a0Schmidl N.\u00a0Hempel L.\u00a0Gr\u00fcnewald A.\u00a0Urbach M.\u00a0Bauer K.\u00a0V.\u00a0Toyka M.\u00a0Blaess R.\u00a0A.\u00a0Claus R.\u00a0K\u00f6nig C.\u00a0Geis Targeted rescue of synaptic plasticity improves cognitive decline after severe systemic inflammation. bioRxiv 2021.03.04.433352 [Preprint] (2021).","DOI":"10.1101\/2021.03.04.433352"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.27227"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2014.09.017"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.717689"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109433"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.24956.1"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.155"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07517"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013984"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9090.1"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac090"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15327"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00136"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.abq7806","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T17:48:10Z","timestamp":1704822490000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.abq7806"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,26]]},"references-count":72,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2023,5,26]]}},"alternative-id":["10.1126\/sciadv.abq7806"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.abq7806","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,26]]},"assertion":[{"value":"2022-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eabq7806"}}