{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:14:36Z","timestamp":1787015676474,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:00:00Z","timestamp":1688947200000},"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":["Journal of Pineal Research"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Circadian clock gene expression in the suprachiasmatic nucleus (SCN) controls 24\u2009h rhythms in body functions, but clock genes are also expressed in extra\u2010hypothalamic tissues, including the melatonin\u2010producing pineal gland. The nocturnal increase in pineal melatonin synthesis is a hallmark in circadian biology, but the role of local clock gene oscillations in the mammalian pineal gland is unknown. The aim of this work is to determine the role of clock genes in endocrine function of the pineal gland with focus on the\n                    <jats:italic>Aanat<\/jats:italic>\n                    transcript encoding the rhythm\u2010generating enzyme of melatonin synthesis. Using the rat as a model, we here established 24\u2009h expression patterns of clock genes in the pineal gland in vivo. Lesion studies showed that rhythmic clock gene expression in the pineal gland to a large extent depends on the SCN; further, clock gene rhythms could be re\u2010established in cultured pineal cells synchronized by rhythmic stimulation with norepinephrine in 12\u2009h pulses, suggesting that pineal cells house a slave oscillator controlled by adrenergic signaling in the gland. Histological analyses showed that clock genes are expressed in pinealocytes and colocalize with\n                    <jats:italic>Aanat<\/jats:italic>\n                    transcripts, thus potentially enabling clock gene products to control cellular melatonin production. To test this, cultured pineal cells were transfected using small interfering RNA to knock down clock gene expression. While successful knockdown of\n                    <jats:italic>Per1<\/jats:italic>\n                    had a minor effect on\n                    <jats:italic>Aanat<\/jats:italic>\n                    ,\n                    <jats:italic>Clock<\/jats:italic>\n                    knockdown produced a marked overexpression of\n                    <jats:italic>Aanat<\/jats:italic>\n                    in the pinealocytes. Our study suggests that SCN\u2010dependent rhythmic\n                    <jats:italic>Clock<\/jats:italic>\n                    gene expression in the pinealocytes regulates the daily profile of\n                    <jats:italic>Aanat<\/jats:italic>\n                    expression.\n                  <\/jats:p>","DOI":"10.1111\/jpi.12893","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T18:42:30Z","timestamp":1687632150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Role and neural regulation of clock genes in the rat pineal gland:\n                    <i>Clock<\/i>\n                    modulates amplitude of rhythmic expression of\n                    <i>Aanat<\/i>\n                    encoding the melatonin\u2010producing enzyme"],"prefix":"10.1111","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6391-1942","authenticated-orcid":false,"given":"Aurea S.","family":"Blancas\u2010Velazquez","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2049-4792","authenticated-orcid":false,"given":"Tenna","family":"Bering","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5705-0951","authenticated-orcid":false,"given":"Signe","family":"Bille","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4047-6324","authenticated-orcid":false,"given":"Martin F.","family":"Rath","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0205883"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-002-0580-5"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.55.2.2"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.69.6.1583"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(78)90648-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.12.3107"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.10.014"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R600036200"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2019.05.001"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.150"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/35081582"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05581.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2003.10.019"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01129-0"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808394200"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00324-9"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06742.x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000327430"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2014.03.005"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0953-816X.2004.03444.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.09.009"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-18-0101"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/0748730411414264"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2593-4_15"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12567"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1888"},{"issue":"4","key":"e_1_2_10_28_1","first-page":"561","article-title":"S\u2010antigen in the developing retina and pineal gland: a monoclonal antibody study","volume":"26","author":"Donoso LA","year":"1985","journal-title":"Invest Ophthalmol Visual Sci"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2011.08.002"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.706433"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12616"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00651.2011"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.7.8770929"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00214906"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02442.x"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80495-X"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80417-1"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6097"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10226"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.22.6762"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5468.1013"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-012-0415-4"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-014-1878-9"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-5-18"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.66020748.x"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/0748730418757006"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.04.027"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14128"},{"issue":"2","key":"e_1_2_10_49_1","first-page":"644","article-title":"The circadian oscillator of the cerebral cortex: molecular, biochemical and behavioral effects of deleting the Arntl clock gene in cortical neurons","volume":"28","author":"Bering T","year":"2018","journal-title":"Cereb Cortex"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14120"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-18-0377"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2013.10.002"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(00)00160-1"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.03.033"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0578"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00197-X"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/365314a0"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.356733"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06457.x"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2010.09.006"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5355.1358"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5242.1681"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2011.00880.x"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00923-5"}],"container-title":["Journal of Pineal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12893","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T08:30:07Z","timestamp":1692261007000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpi.12893"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,10]]},"references-count":63,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1111\/jpi.12893"],"URL":"https:\/\/doi.org\/10.1111\/jpi.12893","archive":["Portico"],"relation":{},"ISSN":["0742-3098","1600-079X"],"issn-type":[{"value":"0742-3098","type":"print"},{"value":"1600-079X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,10]]},"assertion":[{"value":"2023-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12893"}}