{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T12:41:40Z","timestamp":1792413700674,"version":"4.4.0"},"reference-count":54,"publisher":"Society for Neuroscience","issue":"41","license":[{"start":{"date-parts":[[2013,4,10]],"date-time":"2013-04-10T00:00:00Z","timestamp":1365552000000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2012,10,10]]},"abstract":"<jats:p>\n                    The 22q11 deletion syndrome (22q11DS) is characterized by multiple physical and psychiatric abnormalities and is caused by the hemizygous deletion of a 1.5\u20133 Mb region of chromosome 22. It constitutes one of the strongest known genetic risks for schizophrenia; schizophrenia arises in as many as 30% of patients with 22q11DS during adolescence or early adulthood. A mouse model of 22q11DS displays an age-dependent increase in hippocampal long-term potentiation (LTP), a form of synaptic plasticity underlying learning and memory. The sarco(endo)plasmic reticulum Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ATPase (SERCA2), which is responsible for loading Ca\n                    <jats:sup>2+<\/jats:sup>\n                    into the endoplasmic reticulum (ER), is elevated in this mouse model. The resulting increase in ER Ca\n                    <jats:sup>2+<\/jats:sup>\n                    load leads to enhanced neurotransmitter release and increased LTP. However, the mechanism by which the 22q11 microdeletion leads to SERCA2 overexpression and LTP increase has not been determined. Screening of multiple mutant mouse lines revealed that haploinsufficiency of\n                    <jats:italic>Dgcr8<\/jats:italic>\n                    , a microRNA (miRNA) biogenesis gene in the 22q11DS disease-critical region, causes age-dependent, synaptic SERCA2 overexpression and increased LTP. We found that miR-25 and miR-185, regulators of SERCA2, are depleted in mouse models of 22q11DS. Restoration of these miRNAs to presynaptic neurons rescues LTP in\n                    <jats:italic>Dgcr8<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice. Finally, we show that SERCA2 is elevated in the brains of patients with schizophrenia, providing a link between mouse model findings and the human disease. We conclude that miRNA-dependent SERCA2 dysregulation is a pathogenic event in 22q11DS and schizophrenia.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.1312-12.2012","type":"journal-article","created":{"date-parts":[[2012,10,10]],"date-time":"2012-10-10T14:54:32Z","timestamp":1349880872000},"page":"14132-14144","source":"Crossref","is-referenced-by-count":125,"title":["Age-Dependent MicroRNA Control of Synaptic Plasticity in 22q11 Deletion Syndrome and Schizophrenia"],"prefix":"10.1523","volume":"32","author":[{"given":"Laurie R.","family":"Earls","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Gaines","family":"Fricke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond B.","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa T.","family":"Baldwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav S.","family":"Zakharenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2012,10,10]]},"reference":[{"key":"2023041303591372000_32.41.14132.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02871"},{"key":"2023041303591372000_32.41.14132.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07242"},{"key":"2023041303591372000_32.41.14132.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.002"},{"key":"2023041303591372000_32.41.14132.4","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/ajmg.a.30984","article-title":"Clinical features of 78 adults with 22q11 deletion syndrome","volume":"138","author":"Bassett","year":"2005","journal-title":"Am J Med Genet A"},{"key":"2023041303591372000_32.41.14132.5","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2009.84"},{"key":"2023041303591372000_32.41.14132.6","doi-asserted-by":"publisher","DOI":"10.1038\/383431a0"},{"key":"2023041303591372000_32.41.14132.7","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.30.10.822"},{"key":"2023041303591372000_32.41.14132.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2006.04.007"},{"key":"2023041303591372000_32.41.14132.9","first-page":"16","article-title":"Recombinant adeno-associated virus-mediated microRNA delivery into the postnatal mouse brain reveals a role for miR-134 in dendritogenesis in vivo","volume":"3","author":"Christensen","year":"2010","journal-title":"Front Neural Circuits"},{"key":"2023041303591372000_32.41.14132.10","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1425-10.2010"},{"key":"2023041303591372000_32.41.14132.11","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-5-1-r1"},{"key":"2023041303591372000_32.41.14132.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.17.9991"},{"key":"2023041303591372000_32.41.14132.13","doi-asserted-by":"publisher","DOI":"10.1038\/7777"},{"key":"2023041303591372000_32.41.14132.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2004.09.008"},{"key":"2023041303591372000_32.41.14132.15","first-page":"79","article-title":"The isolation of nerve endings from brain: an electron-microscopic study of cell fragments derived by homogenization and centrifugation","volume":"96","author":"Gray","year":"1962","journal-title":"J Anat"},{"key":"2023041303591372000_32.41.14132.16","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1176\/ajp.153.3.321","article-title":"What are the functional consequences of neurocognitive deficits in schizophrenia?","volume":"153","author":"Green","year":"1996","journal-title":"Am J Psychiatry"},{"key":"2023041303591372000_32.41.14132.17","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.schbul.a033430"},{"key":"2023041303591372000_32.41.14132.18","doi-asserted-by":"publisher","DOI":"10.1038\/1137"},{"key":"2023041303591372000_32.41.14132.19","doi-asserted-by":"publisher","DOI":"10.1038\/nature07239"},{"key":"2023041303591372000_32.41.14132.20","doi-asserted-by":"publisher","DOI":"10.1038\/85845"},{"key":"2023041303591372000_32.41.14132.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2010.07.002"},{"key":"2023041303591372000_32.41.14132.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.10.015"},{"key":"2023041303591372000_32.41.14132.23","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.12.2229"},{"key":"2023041303591372000_32.41.14132.24","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1184704"},{"key":"2023041303591372000_32.41.14132.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.12.035"},{"key":"2023041303591372000_32.41.14132.26","doi-asserted-by":"publisher","DOI":"10.1038\/43903"},{"key":"2023041303591372000_32.41.14132.27","doi-asserted-by":"publisher","DOI":"10.1038\/35065105"},{"key":"2023041303591372000_32.41.14132.28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05413.x"},{"key":"2023041303591372000_32.41.14132.29","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.23.1.649"},{"key":"2023041303591372000_32.41.14132.30","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00247-1"},{"key":"2023041303591372000_32.41.14132.31","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80987-3"},{"key":"2023041303591372000_32.41.14132.32","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90155-8"},{"key":"2023041303591372000_32.41.14132.33","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-9-r68"},{"key":"2023041303591372000_32.41.14132.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.09.039"},{"key":"2023041303591372000_32.41.14132.35","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.56.10.940"},{"key":"2023041303591372000_32.41.14132.36","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2647"},{"key":"2023041303591372000_32.41.14132.37","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2003.026880"},{"key":"2023041303591372000_32.41.14132.38","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-2-r27"},{"key":"2023041303591372000_32.41.14132.39","doi-asserted-by":"publisher","DOI":"10.1097\/00005053-199408000-00010"},{"key":"2023041303591372000_32.41.14132.40","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.10.798"},{"key":"2023041303591372000_32.41.14132.41","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.16.2421"},{"key":"2023041303591372000_32.41.14132.42","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)90734-K"},{"key":"2023041303591372000_32.41.14132.43","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8104-6-11"},{"key":"2023041303591372000_32.41.14132.44","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1876"},{"key":"2023041303591372000_32.41.14132.45","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6150-3-44"},{"key":"2023041303591372000_32.41.14132.46","doi-asserted-by":"publisher","DOI":"10.1038\/ng.138"},{"key":"2023041303591372000_32.41.14132.47","doi-asserted-by":"publisher","DOI":"10.1038\/nature07229"},{"key":"2023041303591372000_32.41.14132.48","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2010.09081187"},{"key":"2023041303591372000_32.41.14132.49","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1444406"},{"key":"2023041303591372000_32.41.14132.50","doi-asserted-by":"crossref","unstructured":"Vandecaetsbeek I Vangheluwe P Raeymaekers L Wuytack F Vanoevelen J (2011) The Ca2+ pumps of the endoplasmic reticulum and Golgi apparatus. Cold Spring Harb Perspect Biol 3.","DOI":"10.1101\/cshperspect.a004184"},{"key":"2023041303591372000_32.41.14132.51","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm595"},{"key":"2023041303591372000_32.41.14132.52","first-page":"3","article-title":"Schizophrenia: new phenes and new genes","volume":"46","author":"Weinberger","year":"1999","journal-title":"Biol Psychiatry"},{"key":"2023041303591372000_32.41.14132.53","doi-asserted-by":"publisher","DOI":"10.1038\/ng.162"},{"key":"2023041303591372000_32.41.14132.54","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300938"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.1312-12.2012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T17:18:08Z","timestamp":1681406288000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.1312-12.2012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,10]]},"references-count":54,"journal-issue":{"issue":"41","published-online":{"date-parts":[[2012,10,10]]},"published-print":{"date-parts":[[2012,10,10]]}},"alternative-id":["10.1523\/JNEUROSCI.1312-12.2012"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.1312-12.2012","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.717970786.793469274","asserted-by":"object"}]},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10,10]]}}}