{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T06:51:49Z","timestamp":1794293509929,"version":"4.9.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Ministry of Science and Technology China Brain Initiative Grant","award":["2022ZD0204704"],"award-info":[{"award-number":["2022ZD0204704"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82071380"],"award-info":[{"award-number":["82071380"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82271341"],"award-info":[{"award-number":["82271341"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Knowledge Innovation Program of Wuhan Shuguang Project","award":["2022020801020454"],"award-info":[{"award-number":["2022020801020454"]}]},{"name":"Tongji Hospital (HUST) Foundation for Excellent Young Scientists","award":["2020YQ06"],"award-info":[{"award-number":["2020YQ06"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are activated and play a pivotal role in response to tissue injury. Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed by microglia and promotes microglial activation, survival and phagocytosis. Here, we identify a critical role for TREM2 in microglial activation and function during AQP4-IgG and complement-induced demyelination. TREM2-deficient mice had more severe tissue damage and neurological impairment, as well as fewer oligodendrocytes with suppressed proliferation and maturation. The number of microglia clustering in NMOSD lesions and their proliferation were reduced in TREM2-deficient mice. Moreover, morphology analysis and expression of classic markers showed compromised activation of microglia in TREM2-deficient mice, which was accompanied by suppressed phagocytosis and degradation of myelin debris by microglia. These results overall indicate that TREM2 is a key regulator of microglial activation and exert neuroprotective effects in NMOSD demyelination.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1186\/s12974-023-02772-3","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T06:28:53Z","timestamp":1680503333000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder"],"prefix":"10.1186","volume":"20","author":[{"given":"Yun-Fan","family":"You","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Xiang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Wei","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Hui","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luo-Qi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai-Shi","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"issue":"2","key":"2772_CR1","doi-asserted-by":"publisher","first-page":"90","DOI":"10.3390\/cells8020090","volume":"8","author":"S Mader","year":"2019","unstructured":"Mader S, Brimberg L. Aquaporin-4 water channel in the brain and its implication for health and disease. Cells. 2019;8(2):90.","journal-title":"Cells."},{"issue":"1","key":"2772_CR2","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41572-020-0214-9","volume":"6","author":"S Jarius","year":"2020","unstructured":"Jarius S, Paul F, Weinshenker BG, Levy M, Kim HJ, Wildemann B. Neuromyelitis optica. Nat Rev Dis Primers. 2020;6(1):85.","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"2772_CR3","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1523\/JNEUROSCI.2615-05.2006","volume":"26","author":"MR Kotter","year":"2006","unstructured":"Kotter MR, Li WW, Zhao C, Franklin RJ. Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. J Neurosci. 2006;26(1):328\u201332.","journal-title":"J Neurosci"},{"issue":"2","key":"2772_CR4","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.molmed.2018.11.005","volume":"25","author":"S Voet","year":"2019","unstructured":"Voet S, Prinz M, van Loo G. Microglia in central nervous system inflammation and multiple sclerosis pathology. Trends Mol Med. 2019;25(2):112\u201323.","journal-title":"Trends Mol Med"},{"issue":"6","key":"2772_CR5","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.molmed.2017.03.008","volume":"23","author":"FL Yeh","year":"2017","unstructured":"Yeh FL, Hansen DV, Sheng M. TREM2, microglia, and neurodegenerative diseases. Trends Mol Med. 2017;23(6):512\u201333.","journal-title":"Trends Mol Med"},{"key":"2772_CR6","doi-asserted-by":"crossref","unstructured":"Xu T, Liu C, Deng S, Gan L, Zhang Z, Yang GY, et al. The roles of microglia and astrocytes in myelin phagocytosis in the central nervous system. J Cereb Blood Flow Metab. 2022:271678X221137762.","DOI":"10.1177\/0271678X221137762"},{"key":"2772_CR7","doi-asserted-by":"publisher","first-page":"178","DOI":"10.3389\/fncel.2018.00178","volume":"12","author":"N Laflamme","year":"2018","unstructured":"Laflamme N, Cisbani G, Prefontaine P, Srour Y, Bernier J, St-Pierre MK, et al. mCSF-induced microglial activation prevents myelin loss and promotes its repair in a mouse model of multiple sclerosis. Front Cell Neurosci. 2018;12:178.","journal-title":"Front Cell Neurosci"},{"issue":"6","key":"2772_CR8","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1016\/j.cell.2020.05.003","volume":"181","author":"A Deczkowska","year":"2020","unstructured":"Deczkowska A, Weiner A, Amit I. The physiology, pathology, and potential therapeutic applications of the TREM2 signaling pathway. Cell. 2020;181(6):1207\u201317.","journal-title":"Cell"},{"issue":"6","key":"2772_CR9","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.cell.2015.01.049","volume":"160","author":"Y Wang","year":"2015","unstructured":"Wang Y, Cella M, Mallinson K, Ulrich JD, Young KL, Robinette ML, et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer\u2019s disease model. Cell. 2015;160(6):1061\u201371.","journal-title":"Cell"},{"issue":"Pt 2","key":"2772_CR10","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1093\/brain\/awp309","volume":"133","author":"S Saadoun","year":"2010","unstructured":"Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain. 2010;133(Pt 2):349\u201361.","journal-title":"Brain"},{"issue":"1","key":"2772_CR11","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1186\/s12974-021-02266-0","volume":"18","author":"X Ma","year":"2021","unstructured":"Ma X, Qin C, Chen M, Yu HH, Chu YH, Chen TJ, et al. Regulatory T cells protect against brain damage by alleviating inflammatory response in neuromyelitis optica spectrum disorder. J Neuroinflamm. 2021;18(1):201.","journal-title":"J Neuroinflamm"},{"key":"2772_CR12","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1742-2094-11-16","volume":"11","author":"N Asavapanumas","year":"2014","unstructured":"Asavapanumas N, Ratelade J, Papadopoulos MC, Bennett JL, Levin MH, Verkman AS. Experimental mouse model of optic neuritis with inflammatory demyelination produced by passive transfer of neuromyelitis optica-immunoglobulin G. J Neuroinflamm. 2014;11:16.","journal-title":"J Neuroinflamm"},{"issue":"28","key":"2772_CR13","doi-asserted-by":"publisher","first-page":"14290","DOI":"10.1073\/pnas.1819343116","volume":"116","author":"M Baydyuk","year":"2019","unstructured":"Baydyuk M, Cha DS, Hu J, Yamazaki R, Miller EM, Smith VN, et al. Tracking the evolution of CNS remyelinating lesion in mice with neutral red dye. Proc Natl Acad Sci U S A. 2019;116(28):14290\u20139.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2772_CR14","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.neuint.2018.12.016","volume":"127","author":"P Cengiz","year":"2019","unstructured":"Cengiz P, Zafer D, Chandrashekhar JH, Chanana V, Bogost J, Waldman A, et al. Developmental differences in microglia morphology and gene expression during normal brain development and in response to hypoxia-ischemia. Neurochem Int. 2019;127:137\u201347.","journal-title":"Neurochem Int"},{"issue":"8","key":"2772_CR15","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.1002\/jnr.24683","volume":"99","author":"BM Siemsen","year":"2021","unstructured":"Siemsen BM, Landin JD, McFaddin JA, Hooker KN, Chandler LJ, Scofield MD. Chronic intermittent ethanol and lipopolysaccharide exposure differentially alter Iba1-derived microglia morphology in the prelimbic cortex and nucleus accumbens core of male Long-Evans rats. J Neurosci Res. 2021;99(8):1922\u201339.","journal-title":"J Neurosci Res"},{"key":"2772_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2021.100378","volume":"18","author":"M Tsyglakova","year":"2021","unstructured":"Tsyglakova M, Huskey AM, Hurst EH, Telep NM, Wilding MC, Babington ME, et al. Sex and region-specific effects of variable stress on microglia morphology. Brain Behav Immun Health. 2021;18: 100378.","journal-title":"Brain Behav Immun Health"},{"key":"2772_CR17","first-page":"57648","volume":"136","author":"K Young","year":"2018","unstructured":"Young K, Morrison H. Quantifying microglia morphology from photomicrographs of immunohistochemistry prepared tissue using ImageJ. J Vis Exp. 2018;136:57648.","journal-title":"J Vis Exp."},{"issue":"10","key":"2772_CR18","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1038\/nmeth.3125","volume":"11","author":"TA Ferreira","year":"2014","unstructured":"Ferreira TA, Blackman AV, Oyrer J, Jayabal S, Chung AJ, Watt AJ, et al. Neuronal morphometry directly from bitmap images. Nat Methods. 2014;11(10):982\u20134.","journal-title":"Nat Methods"},{"key":"2772_CR19","doi-asserted-by":"publisher","first-page":"11935","DOI":"10.1038\/ncomms11935","volume":"7","author":"Y Yang","year":"2016","unstructured":"Yang Y, Wang ZH, Jin S, Gao D, Liu N, Chen SP, et al. Opposite monosynaptic scaling of BLP-vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory. Nat Commun. 2016;7:11935.","journal-title":"Nat Commun"},{"issue":"4","key":"2772_CR20","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1007\/s00401-020-02193-z","volume":"140","author":"F Cignarella","year":"2020","unstructured":"Cignarella F, Filipello F, Bollman B, Cantoni C, Locca A, Mikesell R, et al. TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis. Acta Neuropathol. 2020;140(4):513\u201334.","journal-title":"Acta Neuropathol"},{"key":"2772_CR21","first-page":"51482","volume":"88","author":"DP Schafer","year":"2014","unstructured":"Schafer DP, Lehrman EK, Heller CT, Stevens B. An engulfment assay: a protocol to assess interactions between CNS phagocytes and neurons. J Vis Exp. 2014;88:51482.","journal-title":"J Vis Exp."},{"issue":"1","key":"2772_CR22","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1186\/s12974-020-02020-y","volume":"17","author":"M Chen","year":"2020","unstructured":"Chen M, Yang LL, Hu ZW, Qin C, Zhou LQ, Duan YL, et al. Deficiency of microglial Hv1 channel is associated with activation of autophagic pathway and ROS production in LPC-induced demyelination mouse model. J Neuroinflamm. 2020;17(1):333.","journal-title":"J Neuroinflamm"},{"issue":"6","key":"2772_CR23","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1038\/nprot.2013.055","volume":"8","author":"A Mehlem","year":"2013","unstructured":"Mehlem A, Hagberg CE, Muhl L, Eriksson U, Falkevall A. Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease. Nat Protoc. 2013;8(6):1149\u201354.","journal-title":"Nat Protoc"},{"key":"2772_CR24","first-page":"2376","volume":"49","author":"TN Luong","year":"2011","unstructured":"Luong TN, Carlisle HJ, Southwell A, Patterson PH. Assessment of motor balance and coordination in mice using the balance beam. J Vis Exp. 2011;49:2376.","journal-title":"J Vis Exp."},{"issue":"1","key":"2772_CR25","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1021\/acsami.1c15305","volume":"14","author":"S Gupta","year":"2022","unstructured":"Gupta S, Singh V, Ganesh S, Singhal NK, Sandhir R. siRNA mediated GSK3\u03b2 knockdown targets insulin signaling pathway and rescues Alzheimer\u2019s disease pathology: evidence from in vitro and in vivo studies. ACS Appl Mater Interfaces. 2022;14(1):69\u201393.","journal-title":"ACS Appl Mater Interfaces"},{"issue":"3","key":"2772_CR26","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1038\/nprot.2006.205","volume":"1","author":"RA Bevins","year":"2006","unstructured":"Bevins RA, Besheer J. Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study \u201crecognition memory.\u201d Nat Protoc. 2006;1(3):1306\u201311.","journal-title":"Nat Protoc"},{"issue":"11","key":"2772_CR27","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/s41582-018-0072-1","volume":"14","author":"TK Ulland","year":"2018","unstructured":"Ulland TK, Colonna M. TREM2\u2014a key player in microglial biology and Alzheimer disease. Nat Rev Neurol. 2018;14(11):667\u201375.","journal-title":"Nat Rev Neurol"},{"key":"2772_CR28","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1146\/annurev-immunol-032713-120240","volume":"32","author":"D Nayak","year":"2014","unstructured":"Nayak D, Roth TL, McGavern DB. Microglia development and function. Annu Rev Immunol. 2014;32:367\u2013402.","journal-title":"Annu Rev Immunol"},{"key":"2772_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2019.101696","volume":"183","author":"C Cal\u00ec","year":"2019","unstructured":"Cal\u00ec C, Agus M, Kare K, Boges DJ, Lehv\u00e4slaiho H, Hadwiger M, et al. 3D cellular reconstruction of cortical glia and parenchymal morphometric analysis from Serial Block-Face Electron Microscopy of juvenile rat. Prog Neurobiol. 2019;183: 101696.","journal-title":"Prog Neurobiol"},{"issue":"1","key":"2772_CR30","doi-asserted-by":"publisher","first-page":"6224","DOI":"10.1038\/s41598-019-42728-3","volume":"9","author":"Z Winkler","year":"2019","unstructured":"Winkler Z, Kuti D, Polyak A, Juhasz B, Gulyas K, Lenart N, et al. Hypoglycemia-activated hypothalamic microglia impairs glucose counterregulatory responses. Sci Rep. 2019;9(1):6224.","journal-title":"Sci Rep"},{"issue":"1","key":"2772_CR31","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13024-021-00440-9","volume":"16","author":"K Clayton","year":"2021","unstructured":"Clayton K, Delpech JC, Herron S, Iwahara N, Ericsson M, Saito T, et al. Plaque associated microglia hyper-secrete extracellular vesicles and accelerate tau propagation in a humanized APP mouse model. Mol Neurodegener. 2021;16(1):18.","journal-title":"Mol Neurodegener"},{"issue":"3","key":"2772_CR32","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1227\/01.NEU.0000170440.32720.77","volume":"57","author":"M Caffo","year":"2005","unstructured":"Caffo M, Caruso G, German\u00f2 A, Galatioto S, Meli F, Tomasello F. CD68 and CR3\/43 immunohistochemical expression in secretory meningiomas. Neurosurgery. 2005;57(3):551\u20137; discussion\u22127.","journal-title":"Neurosurgery"},{"issue":"1","key":"2772_CR33","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/s12974-021-02135-w","volume":"18","author":"K Suzuki","year":"2021","unstructured":"Suzuki K, Shinohara M, Uno Y, Tashiro Y, Gheni G, Yamamoto M, et al. Deletion of B-cell translocation gene 2 (BTG2) alters the responses of glial cells in white matter to chronic cerebral hypoperfusion. J Neuroinflamm. 2021;18(1):86.","journal-title":"J Neuroinflamm"},{"issue":"5","key":"2772_CR34","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.neuron.2019.12.007","volume":"105","author":"AA Nugent","year":"2020","unstructured":"Nugent AA, Lin K, van Lengerich B, Lianoglou S, Przybyla L, Davis SS, et al. TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge. Neuron. 2020;105(5):837\u2013549.","journal-title":"Neuron"},{"issue":"Pt 2","key":"2772_CR35","first-page":"288","volume":"132","author":"H Neumann","year":"2009","unstructured":"Neumann H, Kotter MR, Franklin RJ. Debris clearance by microglia: an essential link between degeneration and regeneration. Brain. 2009;132(Pt 2):288\u201395.","journal-title":"Brain"},{"issue":"2","key":"2772_CR36","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/0163-7827(85)90011-6","volume":"24","author":"PS Sastry","year":"1985","unstructured":"Sastry PS. Lipids of nervous tissue: composition and metabolism. Prog Lipid Res. 1985;24(2):69\u2013176.","journal-title":"Prog Lipid Res"},{"issue":"9","key":"2772_CR37","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1212\/01.WNL.0000160304.00003.CA","volume":"64","author":"HH Kl\u00fcnemann","year":"2005","unstructured":"Kl\u00fcnemann HH, Ridha BH, Magy L, Wherrett JR, Hemelsoet DM, Keen RW, et al. The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2. Neurology. 2005;64(9):1502\u20137.","journal-title":"Neurology"},{"issue":"2","key":"2772_CR38","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1056\/NEJMoa1211103","volume":"368","author":"T Jonsson","year":"2013","unstructured":"Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, et al. Variant of TREM2 associated with the risk of Alzheimer\u2019s disease. N Engl J Med. 2013;368(2):107\u201316.","journal-title":"N Engl J Med"},{"issue":"1","key":"2772_CR39","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13024-018-0262-8","volume":"13","author":"PJ Cheng-Hathaway","year":"2018","unstructured":"Cheng-Hathaway PJ, Reed-Geaghan EG, Jay TR, Casali BT, Bemiller SM, Puntambekar SS, et al. The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer\u2019s disease. Mol Neurodegener. 2018;13(1):29.","journal-title":"Mol Neurodegener"},{"issue":"Pt 11","key":"2772_CR40","doi-asserted-by":"publisher","first-page":"3081","DOI":"10.1093\/brain\/awn217","volume":"131","author":"L Piccio","year":"2008","unstructured":"Piccio L, Buonsanti C, Cella M, Tassi I, Schmidt RE, Fenoglio C, et al. Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation. Brain. 2008;131(Pt 11):3081\u201391.","journal-title":"Brain"},{"key":"2772_CR41","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2021.105398","volume":"155","author":"A Vautheny","year":"2021","unstructured":"Vautheny A, Duwat C, Aur\u00e9gan G, Jos\u00e9phine C, H\u00e9rard AS, Jan C, et al. THY-Tau22 mouse model accumulates more tauopathy at late stage of the disease in response to microglia deactivation through TREM2 deficiency. Neurobiol Dis. 2021;155: 105398.","journal-title":"Neurobiol Dis"},{"issue":"4","key":"2772_CR42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040124","volume":"4","author":"K Takahashi","year":"2007","unstructured":"Takahashi K, Prinz M, Stagi M, Chechneva O, Neumann H. TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis. PLoS Med. 2007;4(4): e124.","journal-title":"PLoS Med"},{"issue":"12","key":"2772_CR43","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1038\/nrn.2017.136","volume":"18","author":"RJM Franklin","year":"2017","unstructured":"Franklin RJM, Ffrench-Constant C. Regenerating CNS myelin\u2014from mechanisms to experimental medicines. Nat Rev Neurosci. 2017;18(12):753\u201369.","journal-title":"Nat Rev Neurosci"},{"issue":"5","key":"2772_CR44","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/j.cell.2018.05.003","volume":"173","author":"A Deczkowska","year":"2018","unstructured":"Deczkowska A, Keren-Shaul H, Weiner A, Colonna M, Schwartz M, Amit I. Disease-associated microglia: a universal immune sensor of neurodegeneration. Cell. 2018;173(5):1073\u201381.","journal-title":"Cell"},{"issue":"7","key":"2772_CR45","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","volume":"169","author":"H Keren-Shaul","year":"2017","unstructured":"Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland TK, et al. A unique microglia type associated with restricting development of Alzheimer\u2019s disease. Cell. 2017;169(7):1276-90.e17.","journal-title":"Cell"},{"issue":"3","key":"2772_CR46","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s00401-015-1388-1","volume":"129","author":"C Cantoni","year":"2015","unstructured":"Cantoni C, Bollman B, Licastro D, Xie M, Mikesell R, Schmidt R, et al. TREM2 regulates microglial cell activation in response to demyelination in vivo. Acta Neuropathol. 2015;129(3):429\u201347.","journal-title":"Acta Neuropathol"},{"issue":"10","key":"2772_CR47","doi-asserted-by":"publisher","first-page":"e20210227","DOI":"10.1084\/jem.20210227","volume":"218","author":"G Gouna","year":"2021","unstructured":"Gouna G, Klose C, Bosch-Queralt M, Liu L, Gokce O, Schifferer M, et al. TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination. J Exp Med. 2021;218(10):e20210227.","journal-title":"J Exp Med."}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-023-02772-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-023-02772-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-023-02772-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T06:29:57Z","timestamp":1680503397000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-023-02772-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,3]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["2772"],"URL":"https:\/\/doi.org\/10.1186\/s12974-023-02772-3","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,3]]},"assertion":[{"value":"15 February 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal procedures were approved by the Institute of Animal Care Committee of Tongji Medical College, Huazhong University of Science and Technology, China.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"89"}}