{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:17:21Z","timestamp":1793812641315,"version":"4.6.1"},"reference-count":67,"publisher":"Society for Neuroscience","issue":"9","license":[{"start":{"date-parts":[[2011,9,2]],"date-time":"2011-09-02T00:00:00Z","timestamp":1314921600000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2011,3,2]]},"abstract":"<jats:p>\n                    Activation of the complement cascade, a powerful effector mechanism of the innate immune system, is associated with neuroinflammation but also with elimination of inappropriate synapses during development. Synthesis of C1q, a recognition component of the complement system, occurs in brain during ischemia\/reperfusion and Alzheimer's disease, suggesting that C1q may be a response to injury.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , C1q, in the absence of other complement proteins, improves neuronal viability and neurite outgrowth and prevents \u03b2-amyloid-induced neuronal death, suggesting that C1q may have a direct neuroprotective role. Here, investigating the molecular basis for this neuroprotection\n                    <jats:italic>in vitro<\/jats:italic>\n                    , addition of C1q to rat primary cortical neurons significantly upregulated expression of genes associated with cholesterol metabolism, such as cholesterol-25-hydroxylase and insulin induced gene 2, and transiently decreased cholesterol levels in neurons, known to facilitate neurite outgrowth. In addition, the expression of syntaxin-3 and its functional association with synaptosomal-associated protein 25 was increased. C1q also increased the nuclear translocation of cAMP response element-binding protein and CCAAT\/enhancer-binding protein-\u03b4 (C\/EBP-\u03b4), two transcription factors involved in nerve growth factor (NGF) expression and downregulated specific microRNAs, including let-7c that is predicted to target (and thus inhibit) NGF and neurotrophin-3 (NT-3) mRNA. Accordingly, C1q increased expression of NGF and NT-3, and small interfering RNA inhibition of C\/EBP-\u03b4, NGF, or NT-3 expression prevented the C1q-dependent neurite outgrowth. No such neuroprotective effect is seen in the presence of C3a or C5a. Finally, the induced neuronal gene expression required conformationally intact C1q. These results show that C1q can directly promote neuronal survival, thereby demonstrating new interactions between immune proteins and neuronal cells that may facilitate neuroprotection.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.3932-10.2011","type":"journal-article","created":{"date-parts":[[2011,3,3]],"date-time":"2011-03-03T15:27:37Z","timestamp":1299166057000},"page":"3459-3469","source":"Crossref","is-referenced-by-count":144,"title":["Complement Protein C1q-Mediated Neuroprotection Is Correlated with Regulation of Neuronal Gene and MicroRNA Expression"],"prefix":"10.1523","volume":"31","author":[{"given":"Marie E.","family":"Benoit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea J.","family":"Tenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2011,3,2]]},"reference":[{"key":"2023041303491445000_31.9.3459.1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2008"},{"key":"2023041303491445000_31.9.3459.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05668.x"},{"key":"2023041303491445000_31.9.3459.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2008.05.027"},{"key":"2023041303491445000_31.9.3459.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000066"},{"key":"2023041303491445000_31.9.3459.5","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1042\/bj2160385","article-title":"Biosynthesis in vitro of complement subcomponents C1q, C1s and C1 inhibitor by resting and stimulated human monocytes","volume":"216","author":"Bensa","year":"1983","journal-title":"Biochem J"},{"key":"2023041303491445000_31.9.3459.6","doi-asserted-by":"publisher","DOI":"10.1038\/ng1201-365"},{"key":"2023041303491445000_31.9.3459.7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0913449107"},{"key":"2023041303491445000_31.9.3459.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10920"},{"key":"2023041303491445000_31.9.3459.9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.5483\/BMBRep.2009.42.3.131","article-title":"The role of microRNAs in synaptic development and function","volume":"42","author":"Corbin","year":"2009","journal-title":"BMB Rep"},{"key":"2023041303491445000_31.9.3459.10","doi-asserted-by":"publisher","DOI":"10.1038\/nature04598"},{"key":"2023041303491445000_31.9.3459.11","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-4-5-p3"},{"key":"2023041303491445000_31.9.3459.12","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(94)00269-T"},{"key":"2023041303491445000_31.9.3459.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2003.09.023"},{"key":"2023041303491445000_31.9.3459.14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901005"},{"key":"2023041303491445000_31.9.3459.15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002080"},{"key":"2023041303491445000_31.9.3459.16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605741200"},{"key":"2023041303491445000_31.9.3459.17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902232"},{"key":"2023041303491445000_31.9.3459.18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06494.x"},{"key":"2023041303491445000_31.9.3459.19","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.220"},{"key":"2023041303491445000_31.9.3459.20","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1046\/j.1471-4159.1997.68052046.x","article-title":"Kainic acid and decorticating lesions stimulate the synthesis of C1q protein in adult rat brain","volume":"68","author":"Goldsmith","year":"1997","journal-title":"J Neurochem"},{"key":"2023041303491445000_31.9.3459.21","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1046\/j.1471-4159.1998.70020699.x","article-title":"Inflammatory signals induce neurotrophin expression in human microglial cells","volume":"70","author":"Heese","year":"1998","journal-title":"J Neurochem"},{"key":"2023041303491445000_31.9.3459.22","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"2023041303491445000_31.9.3459.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5427.595"},{"key":"2023041303491445000_31.9.3459.24","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2336"},{"key":"2023041303491445000_31.9.3459.25","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-3-8"},{"key":"2023041303491445000_31.9.3459.26","doi-asserted-by":"publisher","DOI":"10.2174\/156800705774322058"},{"key":"2023041303491445000_31.9.3459.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2009.09.041"},{"key":"2023041303491445000_31.9.3459.28","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1644"},{"key":"2023041303491445000_31.9.3459.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.04.027"},{"key":"2023041303491445000_31.9.3459.30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509164200"},{"key":"2023041303491445000_31.9.3459.31","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-34134-X_6"},{"key":"2023041303491445000_31.9.3459.32","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2037"},{"key":"2023041303491445000_31.9.3459.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.06.021"},{"key":"2023041303491445000_31.9.3459.34","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02765.x"},{"key":"2023041303491445000_31.9.3459.35","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0829-08.2008"},{"key":"2023041303491445000_31.9.3459.36","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200216500"},{"key":"2023041303491445000_31.9.3459.37","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600207200"},{"key":"2023041303491445000_31.9.3459.38","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20022"},{"key":"2023041303491445000_31.9.3459.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2007.10.015"},{"key":"2023041303491445000_31.9.3459.40","doi-asserted-by":"publisher","DOI":"10.1038\/nature02319"},{"key":"2023041303491445000_31.9.3459.41","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.6.781"},{"key":"2023041303491445000_31.9.3459.42","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4644(19990601)73:3<303::AID-JCB2>3.0.CO;2-2"},{"key":"2023041303491445000_31.9.3459.43","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2233"},{"key":"2023041303491445000_31.9.3459.44","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1111\/j.1471-4159.2007.05012.x","article-title":"Complement component C1q inhibits beta-amyloid- and serum amyloid P-induced neurotoxicity via caspase- and calpain-independent mechanisms","volume":"104","author":"Pisalyaput","year":"2008","journal-title":"J Neurochem"},{"key":"2023041303491445000_31.9.3459.45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03763.x"},{"key":"2023041303491445000_31.9.3459.46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700899104"},{"key":"2023041303491445000_31.9.3459.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.01.099"},{"key":"2023041303491445000_31.9.3459.48","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3158-09.2009"},{"key":"2023041303491445000_31.9.3459.49","doi-asserted-by":"publisher","DOI":"10.1261\/rna.5248604"},{"key":"2023041303491445000_31.9.3459.50","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1042\/bj1550005","article-title":"Isolation, by partial pepsin digestion, of the three collagen-like regions present in subcomponent C1q of the first component of human complement","volume":"155","author":"Reid","year":"1976","journal-title":"Biochem J"},{"key":"2023041303491445000_31.9.3459.51","doi-asserted-by":"publisher","DOI":"10.1080\/07853890510007278"},{"key":"2023041303491445000_31.9.3459.52","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"2023041303491445000_31.9.3459.53","doi-asserted-by":"crossref","first-page":"846","DOI":"10.7164\/antibiotics.24.846","article-title":"Fluorometric evidence for the binding of cholesterol to the filipin complex","volume":"24","author":"Schroeder","year":"1971","journal-title":"J Antibiot (Tokyo)"},{"key":"2023041303491445000_31.9.3459.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2004.06.003"},{"key":"2023041303491445000_31.9.3459.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2008.11.003"},{"key":"2023041303491445000_31.9.3459.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.036"},{"key":"2023041303491445000_31.9.3459.57","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0690-07.2007"},{"key":"2023041303491445000_31.9.3459.58","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02824.x"},{"key":"2023041303491445000_31.9.3459.59","doi-asserted-by":"crossref","first-page":"648","DOI":"10.4049\/jimmunol.127.2.648","article-title":"Purification and radiolabeling of human C1q","volume":"127","author":"Tenner","year":"1981","journal-title":"J Immunol"},{"key":"2023041303491445000_31.9.3459.60","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-2985(98)80032-6"},{"key":"2023041303491445000_31.9.3459.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.03.019"},{"key":"2023041303491445000_31.9.3459.62","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-009-8085-y"},{"key":"2023041303491445000_31.9.3459.63","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162350199"},{"key":"2023041303491445000_31.9.3459.64","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490270106"},{"key":"2023041303491445000_31.9.3459.65","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.4049\/jimmunol.146.10.3356","article-title":"Complement subcomponent C1q stimulates immunoglobulin production by human B lymphocytes","volume":"146","author":"Young","year":"1991","journal-title":"J Immunol"},{"key":"2023041303491445000_31.9.3459.66","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05558.x"},{"key":"2023041303491445000_31.9.3459.67","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(82)91536-4"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.3932-10.2011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T15:16:54Z","timestamp":1712243814000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.3932-10.2011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,2]]},"references-count":67,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2011,3,2]]},"published-print":{"date-parts":[[2011,3,2]]}},"alternative-id":["10.1523\/JNEUROSCI.3932-10.2011"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.3932-10.2011","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,2]]}}}