{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T06:30:40Z","timestamp":1784961040795,"version":"3.55.0"},"reference-count":58,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Growing evidence indicates that circulating lactoferrin (Lf) is implicated in peripheral cholesterol metabolism disorders. It has emerged that the distribution of Lf changes in astrocytes of aging brains and those exhibiting neurodegeneration; however, its physiological and\/or pathological role remains unknown. Here, we demonstrate that astrocyte\u2010specific knockout of <jats:italic>Lf<\/jats:italic> (designated cKO) led to decreased body weight and cognitive abnormalities during early life in mice. Accordingly, there was a reduction in neuronal outgrowth and synaptic structure in cKO mice. Importantly, Lf deficiency in the primary astrocytes led to decreased sterol regulatory element binding protein 2 (Srebp2) activation and cholesterol production, and cholesterol content in cKO mice and\/or in astrocytes was restored by exogenous Lf or a Srebp2 agonist. Moreover, neuronal dendritic complexity and total dendritic length were decreased after culture with the culture medium of the primary astrocytes derived from cKO mice and that this decrease was reversed after cholesterol supplementation. Alternatively, these alterations were associated with an activation of AMP\u2010activated protein kinase (AMPK) and inhibition of SREBP2 nuclear translocation. These data suggest that astrocytic Lf might directly or indirectly control in situ cholesterol synthesis, which may be implicated in neurodevelopment and several neurological diseases.<\/jats:p>","DOI":"10.1002\/glia.24259","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T08:12:46Z","timestamp":1660119166000},"page":"2392-2408","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Astrocyte\u2010specific loss of lactoferrin influences neuronal structure and function by interfering with cholesterol synthesis"],"prefix":"10.1002","volume":"70","author":[{"given":"Shuang\u2010Feng","family":"Xu","sequence":"first","affiliation":[{"name":"College of Life and Health Sciences Institute of Neuroscience, Northeastern University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong\u2010Qiu","family":"Pang","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences Institute of Neuroscience, Northeastern University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Gang","family":"Fan","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences Institute of Neuroscience, Northeastern University  Shenyang China"},{"name":"Health Sciences Institute, Key Laboratory of Major Chronic Diseases of Nervous System China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences Institute of Neuroscience, Northeastern University  Shenyang China"},{"name":"Health Sciences Institute, Key Laboratory of Major Chronic Diseases of Nervous System China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Han","family":"Meng","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences Institute of Neuroscience, Northeastern University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen\u2010Yang","family":"Bai","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences Institute of Neuroscience, Northeastern University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010Yu","family":"Jia","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences Institute of Neuroscience, Northeastern University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences Institute of Neuroscience, Northeastern University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan\u2010You","family":"Wang","sequence":"additional","affiliation":[{"name":"Health Sciences Institute, Key Laboratory of Major Chronic Diseases of Nervous System China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2929-3786","authenticated-orcid":false,"given":"Chuang","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences Institute of Neuroscience, Northeastern University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-11-36"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.22.14.5100-5113.2002"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/98.2.213"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.099"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2016.00185"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118478"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2019.05.011"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2017.07.011"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.04.009"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1620506114"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.01.014"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0169-328x(99)00221-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0169-328x(01)00216-9"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.9b00248"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.08.021"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/d0fo00910e"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.8"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/373721a0"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2018.02.002"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407962200"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-17-0281"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddrr.1114"},{"issue":"5","key":"e_1_2_9_24_1","first-page":"1574","article-title":"Lactotransferrin immunocytochemistry in Alzheimer and normal human brain","volume":"142","author":"Kawamata T.","year":"1993","journal-title":"The American Journal of Pathology"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12030610"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050468"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)90202-x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000018815"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1039\/c9fo01616c"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0190-7"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2017.72"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.294.5545.1354"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6458"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu10111628"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2007.095943"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.5650\/jos.62.97"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00609"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114510002734"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1245657"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/266730a0"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410370212"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2016.00566"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.6.2198"},{"issue":"10","key":"e_1_2_9_44_1","first-page":"702","article-title":"An adult case of probable Bassen\u2010Kornzweig syndrome, presenting resting tremor","volume":"46","author":"Soejima N.","year":"2006","journal-title":"Rinsh\u014d Shinkeigaku"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-5371-1"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2016.02.041"},{"issue":"4","key":"e_1_2_9_47_1","first-page":"317","article-title":"Immunohistochemical detection of lactoferrin in human astrocytomas and multiforme glioblastomas","volume":"43","author":"Tuccari G.","year":"1999","journal-title":"European Journal of Histochemistry"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2019.04.010"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.138"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23120"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2012.02.014"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1722"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.02.073"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1858-9"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep10729"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2010.06.079"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.172510899"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117678"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.101090"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.24259","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/glia.24259","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.24259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T04:16:19Z","timestamp":1692677779000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.24259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,10]]},"references-count":58,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/glia.24259"],"URL":"https:\/\/doi.org\/10.1002\/glia.24259","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,10]]},"assertion":[{"value":"2021-11-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}