{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:37:53Z","timestamp":1793047073982,"version":"4.5.0"},"reference-count":79,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"751","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,6,12]]},"abstract":"<jats:p>Robust structural remodeling and synaptic plasticity occurs within spinal autonomic circuitry after severe high-level spinal cord injury (SCI). As a result, normally innocuous visceral or somatic stimuli elicit uncontrolled activation of spinal sympathetic reflexes that contribute to systemic disease and organ-specific pathology. How hyperexcitable sympathetic circuitry forms is unknown, but local cues from neighboring glia likely help mold these maladaptive neuronal networks. Here, we used a mouse model of SCI to show that microglia surrounded active glutamatergic interneurons and subsequently coordinated multi-segmental excitatory synaptogenesis and expansion of sympathetic networks that control immune, neuroendocrine, and cardiovascular functions. Depleting microglia during critical periods of circuit remodeling after SCI prevented maladaptive synaptic and structural plasticity in autonomic networks, decreased the frequency and severity of autonomic dysreflexia, and prevented SCI-induced immunosuppression. Forced turnover of microglia in microglia-depleted mice restored structural and functional indices of pathological dysautonomia, providing further evidence that microglia are key effectors of autonomic plasticity. Additional data show that microglia-dependent autonomic plasticity required expression of triggering receptor expressed on myeloid cells 2 (Trem2) and \u03b12\u03b4-1\u2013dependent synaptogenesis. These data suggest that microglia are primary effectors of autonomic neuroplasticity and dysautonomia after SCI in mice. Manipulating microglia may be a strategy to limit autonomic complications after SCI or other forms of neurologic disease.<\/jats:p>","DOI":"10.1126\/scitranslmed.adi3259","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T17:59:02Z","timestamp":1718215142000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":58,"title":["Microglia promote maladaptive plasticity in autonomic circuitry after spinal cord injury in mice"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9201-2476","authenticated-orcid":true,"given":"Faith H.","family":"Brennan","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."},{"name":"Belford Center for Spinal Cord Injury, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."},{"name":"Department of Biomedical and Molecular Sciences and Center for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1332-7884","authenticated-orcid":true,"given":"Emily A.","family":"Swarts","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences and Center for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1652-0882","authenticated-orcid":true,"given":"Kristina A.","family":"Kigerl","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."},{"name":"Belford Center for Spinal Cord Injury, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6323-4731","authenticated-orcid":true,"given":"Katherine A.","family":"Mifflin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."},{"name":"Belford Center for Spinal Cord Injury, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."},{"name":"Belford Center for Spinal Cord Injury, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8992-2479","authenticated-orcid":true,"given":"Benjamin T.","family":"Noble","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."},{"name":"Belford Center for Spinal Cord Injury, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3172-8435","authenticated-orcid":true,"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."},{"name":"Belford Center for Spinal Cord Injury, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1832-6861","authenticated-orcid":true,"given":"Kristina G.","family":"Witcher","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."},{"name":"Institute for Behavioral Medicine Research, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Godbout","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."},{"name":"Institute for Behavioral Medicine Research, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1329-7395","authenticated-orcid":true,"given":"Phillip G.","family":"Popovich","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."},{"name":"Belford Center for Spinal Cord Injury, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."},{"name":"Institute for Behavioral Medicine Research, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(05)52016-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(05)52034-X"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4643"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06232.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1974-13.2013"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.05.019"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws267"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv375"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003652"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4390-05.2006"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4289"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108667"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2134-21.2022"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00101-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.1204"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/08977150152693782"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00622-2"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21771"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.12.022"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2376-17.2018"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.11.030"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24179"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5486"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.06.018"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.05.087"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl6773"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.040"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3109\/10641969509087077"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00294-S"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(05)52001-6"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201802057"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.025"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31797-0"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-02-0569"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.12.001"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922788117"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-266296"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11674-z"},{"key":"e_1_3_2_40_2","first-page":"e2270","article-title":"Quantifying synapses: An immunocytochemistry-based assay to quantify synapse number","volume":"2010","author":"Ippolito D. M.","year":"2010","unstructured":"D. M. Ippolito, C. Eroglu, Quantifying synapses: An immunocytochemistry-based assay to quantify synapse number. J. Vis. Exp. 2010, e2270 (2010).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.04047"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature24638"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200192"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600279"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-011-0121-1"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3102020"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00436-5"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3808"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.08.009"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2015.4111"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108041"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1194637"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.04.016"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2193-20.2020"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2020.7504"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00715-5"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32284-2"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56502"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2011.02.009"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax6752"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(75)90097-7"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01095.2010"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702680"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(02)00040-1"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.042"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00751-3"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.026"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.04.001"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal3589"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.050"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.10.018"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111686"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900527R"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23664"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2004.21.1371"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.261289"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0131-20.2020"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2013.04.006"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3599"},{"key":"e_1_3_2_80_2","first-page":"51482","article-title":"An engulfment assay: A protocol to assess interactions between CNS phagocytes and neurons","author":"Schafer D. P.","year":"2014","unstructured":"D. P. Schafer, E. K. Lehrman, C. T. Heller, B. Stevens, An engulfment assay: A protocol to assess interactions between CNS phagocytes and neurons. J. Vis. Exp. 88, 51482 (2014).","journal-title":"J. Vis. Exp. 88"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adi3259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T17:59:26Z","timestamp":1718215166000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adi3259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,12]]},"references-count":79,"journal-issue":{"issue":"751","published-print":{"date-parts":[[2024,6,12]]}},"alternative-id":["10.1126\/scitranslmed.adi3259"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adi3259","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,12]]},"assertion":[{"value":"2023-04-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadi3259"}}