{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T05:18:06Z","timestamp":1791955086862,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Although hypoxia can exacerbate symptoms of various neurological disorders, accumulating evidence has indicated that intermittent hypoxia (IH) may exert protective effects against brain diseases. In the present study, we aimed to determine whether exposure to IH exerts beneficial effects in a transgenic murine model of Alzheimer's disease (AD). Because comorbid anxiety is prevalent among patients with AD, we explored the effects of IH on anxiety\u2010like behaviors and associated factors in APP\/PS1 mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>APP\/PS1 mice were subjected to IH for two weeks. We assessed cognitive performance and anxiety\u2010related behavior using standard behavioral assessments. Amyloid beta (A\u03b2) levels in the hippocampus were assessed using immunofluorescence and enzyme\u2010linked immunosorbent assays (ELISA). We also assessed cell morphology and brain\u2010derived neurotrophic factor (BDNF) expression in the hippocampus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exposure to IH significantly increased cognitive performance and decreased anxiety\u2010related behaviors in APP\/PS1 mice. Immunofluorescence and ELISA results revealed that IH pretreatment significantly lowered A\u03b2 levels in the cortex and hippocampus. Morphological studies validated the neuroprotective effect of IH exposure on hippocampal neurogenesis. Molecular studies revealed IH\u2010enhanced BDNF expression and inhibition of apoptosis\u2010related protein expression in the hippocampus of APP\/PS1 mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrates that IH improves cognition and reduces anxiety in a murine model of AD. Thus, further studies are required to determine whether IH can be used as a preventive\/adjuvant therapy in patients with AD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.1513","type":"journal-article","created":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T23:53:55Z","timestamp":1577404435000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Intermittent hypoxia improves cognition and reduces anxiety\u2010related behavior in APP\/PS1 mice"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6521-8375","authenticated-orcid":false,"given":"Sheng\u2010Xi","family":"Meng","sequence":"first","affiliation":[{"name":"Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Tao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Vasculocardiology Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90289-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.2332"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803702105"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-016-0171-4"},{"key":"e_1_2_9_6_1","first-page":"e2920","article-title":"Morris water maze test for learning and memory deficits in Alzheimer\u2019s disease model mice","volume":"53","author":"Bromley\u2010Brits K.","year":"2011","journal-title":"Journal of Visualized Experiments: Jove"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.03.015"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/14330237.2007.10820161"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-018-1100-8"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)01618-4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00402.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2010.08.005"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720506775697151"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2018.09.002"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.08.017"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(91)90125-A"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.16.9357"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.02.081"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.08.009"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.06.010"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-014-0065-y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2002.7938"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.05.019"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b15-00013"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2013.09.018"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.05.020"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11055-010-9320-6"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10517-006-0318-6"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.05.013"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-009-9312-6"},{"key":"e_1_2_9_31_1","first-page":"152","article-title":"Hippocampal neuronal loss in the CA1 and CA3 areas of Alzheimer\u2019s disease patients","volume":"24","author":"Padurariu M.","year":"2012","journal-title":"Psychiatria Danubina"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.30"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.12.024"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2010.11.002"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13258"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2016.00003"},{"key":"e_1_2_9_37_1","first-page":"347","article-title":"Brain\u2010derived neurotrophic factor prevents beta\u2010amyloid\u2010induced apoptosis of pheochromocytoma cells by regulating Bax\/Bcl\u20102 expression","volume":"7","author":"Sun Z.","year":"2012","journal-title":"Neural Regeneration Research"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.05.1375"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/54.7.M348"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20101"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-006-0652-8"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.20174"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370214562339"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6414-09.2010"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.1513","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/brb3.1513","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.1513","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T14:58:38Z","timestamp":1694012318000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.1513"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,26]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["10.1002\/brb3.1513"],"URL":"https:\/\/doi.org\/10.1002\/brb3.1513","archive":["Portico"],"relation":{},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"value":"2162-3279","type":"print"},{"value":"2162-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,26]]},"assertion":[{"value":"2019-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01513"}}