{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:16:42Z","timestamp":1791919002474,"version":"4.3.4"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T00:00:00Z","timestamp":1580342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370444"],"award-info":[{"award-number":["81370444"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Infections could contribute to Alzheimer's disease (AD) neuropathology in human. However, experimental evidence for a causal relationship between infections during the prenatal phase and the onset of AD is lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CD\u20101 mothers were intraperitoneally received lipopolysaccharide (LPS) with two doses (25 and 50\u00a0\u03bcg\/kg) or normal saline every day during gestational days 15\u201317. A battery of behavioral tasks was used to assess the species\u2010typical behavior, sensorimotor capacity, anxiety, locomotor activity, recognition memory, and spatial learning and memory in 1\u2010, 6\u2010, 12\u2010, 18\u2010, and 22\u2010month\u2010old offspring mice. An immunohistochemical technology was performed to detect neuropathological indicators consisting of amyloid\u2010\u03b2 (A\u03b2), phosphorylated tau (p\u2010tau), and glial fibrillary acidic protein (GFAP) in the hippocampus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to the same\u2010aged controls, LPS\u2010treated offspring had similar behavioral abilities and the levels of A\u03b242, p\u2010tau, and GFAP at 1 and 6\u00a0months old. From 12\u00a0months onward, LPS\u2010treated offspring gradually showed decreased species\u2010typical behavior, sensorimotor ability, locomotor activity, recognition memory, and spatial learning and memory, and increased anxieties and the levels of A\u03b242, p\u2010tau, and GFAP relative to the same\u2010aged controls. Moreover, this damage effect (especially cognitive decline) persistently progressed onwards. The changes in these neuropathological indicators significantly correlated with impaired spatial learning and memory.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Prenatal exposure to low doses of LPS caused AD\u2010related features including behavioral and neuropathological changes from midlife to senectitude.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.1546","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T08:33:01Z","timestamp":1580373181000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Lipopolysaccharide exposure during late embryogenesis triggers and drives Alzheimer\u2010like behavioral and neuropathological changes in CD\u20101 mice"],"prefix":"10.1002","volume":"10","author":[{"given":"Fang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology the First Affiliated Hospital of Anhui Medical University Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe\u2010Zhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology the First Affiliated Hospital of Anhui Medical University Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurology the Second Affiliated Hospital of Anhui Medical University Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi\u2010Gang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine the First Affiliated Hospital of Anhui Medical University Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing\u2010Fang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Mental Psychology the Taihe County Chinese Medicine Hospital Fuyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5638-1357","authenticated-orcid":false,"given":"Gui\u2010Hai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology (Sleep Disorders) the Affiliated Chaohu Hospital of Anhui Medical University Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1388-y"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/dev.20568"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu437"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.11.025"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-9880-8"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2017.03.011"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.03.005"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2013.09.034"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.01.014"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.110.087031"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.disamonth.2010.06.001"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2010.11.001"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.03.001"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(04)00309-9"},{"issue":"4","key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.55782\/ane-2011-1868","article-title":"Lipopolysaccharide injected to pregnant mice affects behavior of their offspring in adulthood","volume":"71","author":"Chlodzinska N.","year":"2011","journal-title":"Acta Neurobiologiae Experimentalis"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710493114"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glx104"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-014-0155-x"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2011.08.015"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2007.04.016"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.05.005"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.05.045"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.06.005"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.01.006"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2007.01.005"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179970"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2004.09.008"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-004-0951-y"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.01.010"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.187"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-151"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-5-37"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04533"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.03.011"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-016-9920-3"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.90350.2008"},{"key":"e_1_2_11_38_1","first-page":"379","article-title":"Postnatal exposure to poly (I:C) impairs learning and memory through changes in synaptic plasticity gene expression in developing rat brain","volume":"155","author":"Meghraj S. B.","year":"2017","journal-title":"Neurobiology of Learning and Memory"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2016.06.014"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0099-06.2006"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.01.015"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720511797633250"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.05.058"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00214"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2011.07738.x"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1159\/000337230"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2018.02.007"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00259"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.02.012"},{"key":"e_1_2_11_50_1","first-page":"284","article-title":"Chronic acarbose treatment alleviates age\u2010related behavioral and biochemical changes in SAMP8 mice","volume":"01","author":"Tong J.\u2010J.","year":"2015","journal-title":"Behavioral Brain Research"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.12872"},{"issue":"2","key":"e_1_2_11_52_1","first-page":"86","article-title":"Lipopolysaccharide endotoxemia induces amyloid\u2010\u03b2 and p\u2010tau formation in the rat brain","volume":"8","author":"Wang L. M.","year":"2018","journal-title":"American Journal of Nuclear Medicine and Molecular Imaging"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-1002-7"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2014.10.004"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.09.009"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-4-3"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-6-27"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbrb3.1546","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.1546","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/brb3.1546","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.1546","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T21:22:41Z","timestamp":1722374561000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.1546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,30]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1002\/brb3.1546"],"URL":"https:\/\/doi.org\/10.1002\/brb3.1546","archive":["Portico"],"relation":{},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"value":"2162-3279","type":"print"},{"value":"2162-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,30]]},"assertion":[{"value":"2019-09-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01546"}}