{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T20:49:41Z","timestamp":1765486181381,"version":"3.37.3"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T00:00:00Z","timestamp":1518566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"VA Merit Award","award":["BX001814-01A1"],"award-info":[{"award-number":["BX001814-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the effect of <jats:italic>Bmal1<\/jats:italic> knockdown (<jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content>) on sleep, activity, immobility, hypothalamic levels of orexin, corticotrophin\u2010releasing hormone (<jats:styled-content style=\"fixed-case\">CRH<\/jats:styled-content>), and <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>ergic glutamate decarboxylase (<jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used <jats:italic>Bmal1<\/jats:italic> si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>, or control si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> intracerebroventricular (<jats:styled-content style=\"fixed-case\">ICV<\/jats:styled-content>) injection to knock down <jats:italic>Bmal1<\/jats:italic> in C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice. Sleep polysomnography, wheel\u2010running activity, and tail suspension test were performed. Polysomnographic (<jats:styled-content style=\"fixed-case\">PSG<\/jats:styled-content>) recordings in both groups were preceded by <jats:styled-content style=\"fixed-case\">ICV<\/jats:styled-content> injection made during both the light phase and the dark phase. We also measured brain orexin A and <jats:styled-content style=\"fixed-case\">CRH<\/jats:styled-content> using an <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content> and measured <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content> using immunoblotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with control group, <jats:italic>Bmal1 <\/jats:italic><jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content> group had reduced wheel activity and increased immobility. Compared with control, the <jats:italic>Bmal1 <\/jats:italic><jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content> group had reduced wheel activity and increased immobility. During the first 24\u00a0hours after treatment, we observed that control si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> induced a much greater increase in sleep during the dark phase, which was associated with lower orexin levels. However, beginning 24\u00a0hours after treatment, we observed an increase in sleep and a decrease in time spent awake during the dark phase in the <jats:italic>Bmal1 <\/jats:italic><jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content> group. These changes were not associated with changes in brain levels of orexin A, <jats:styled-content style=\"fixed-case\">CRH<\/jats:styled-content>, or <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>Bmal1 <\/jats:italic><jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content> led to reduced activity, increased immobility, and dramatic reduction in time spent awake as well as an increase in sleep during the dark phase. Early after injection, there was a slight change in sleep but brain levels of orexin, <jats:styled-content style=\"fixed-case\">CRH<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">GAD<\/jats:styled-content> remain unchanged. Control si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> also affected sleep associated with changes in orexin levels.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12815","type":"journal-article","created":{"date-parts":[[2018,2,15]],"date-time":"2018-02-15T04:22:43Z","timestamp":1518668563000},"page":"549-563","source":"Crossref","is-referenced-by-count":8,"title":["Bmal1 knockdown suppresses wake and increases immobility without altering orexin A, corticotrophin\u2010releasing hormone, or glutamate decarboxylase"],"prefix":"10.1111","volume":"24","author":[{"given":"Afaf","family":"Akladious","sequence":"first","affiliation":[{"name":"Louis Stokes Cleveland VA Medical Center  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sausan","family":"Azzam","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine Case Western Reserve University  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufen","family":"Hu","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland VA Medical Center  Cleveland OH USA"},{"name":"Division of Pulmonary, Critical Care and Sleep Medicine Case Western Reserve University  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8267-5524","authenticated-orcid":false,"given":"Pingfu","family":"Feng","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland VA Medical Center  Cleveland OH USA"},{"name":"Division of Pulmonary, Critical Care and Sleep Medicine Case Western Reserve University  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,2,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.13.8581"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1006\/bbrc.1997.6371","article-title":"cDNA cloning and tissue\u2010specific expression of a novel basic helix\u2010loop\u2010helix\/PAS protein (BMAL1) and identification of alternatively spliced variants with alternative translation initiation site usage","volume":"233","author":"Ikeda M","year":"1997","journal-title":"Biochem Biophys Res Commun"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80245-7"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385940-2.00009-7"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/11318620-000000000-00000"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.2.429-440.2000"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1504"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1432206"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/28.4.395"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.10.058"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.02196.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(03)03295-5"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)00425-P"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/phrs.1997.0155"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)02317-4"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00319-0"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-014-0946-y"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00330-1"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06310"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2014_364"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0784-11.2011"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.20252"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394623-2.00008-1"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2008.12.002"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1520081"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1358\/dnp.2005.18.4.908659"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1385\/MN:32:3:285"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00258"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.11.006"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2011.05.025"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1417.027"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-5-65"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.03.033"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.03.016"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5023-07.2008"},{"key":"e_1_2_6_37_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and Statistical Manual of Mental Disorders (DSM\u20105)","author":"American_Psychatric_Association","year":"2013"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2014.08.008"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0160-5402(86)90038-0"},{"key":"e_1_2_6_40_1","article-title":"Delivery of therapeutic agents through intracerebroventricular (ICV) and intravenous (IV) injection in mice","volume":"2968","author":"Glascock JJ","year":"2011","journal-title":"J Vis Exp"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2015.08.002"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20961"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2014.03.014"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1816-05.2005"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2004.06.010"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881106082899"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086545"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100113"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI70317"},{"key":"e_1_2_6_50_1","first-page":"501","article-title":"Sleep\u2010promoting functions of the hypothalamic median preoptic nucleus: inhibition of arousal systems","volume":"142","author":"McGinty D","year":"2004","journal-title":"Arch Ital Biol"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.006"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0077-16.2016"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067173"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcns.12815","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.12815","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T21:33:46Z","timestamp":1695504826000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.12815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,14]]},"references-count":52,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/cns.12815"],"URL":"https:\/\/doi.org\/10.1111\/cns.12815","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"type":"print","value":"1755-5930"},{"type":"electronic","value":"1755-5949"}],"subject":[],"published":{"date-parts":[[2018,2,14]]}}}