{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:30:18Z","timestamp":1790303418293,"version":"4.1.0"},"reference-count":27,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T00:00:00Z","timestamp":1518393600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:p>\n                    Although still a matter of controversy, disrupted in schizophrenia protein 1 (DISC1) was suggested as a potential inhibitor of phosphodiesterase 4 (PDE4). We used Disc1 locus impairment (LI) mice to investigate the interaction between PDE4 and DISC 1 in\u00a0vivo and in\u00a0vitro. [\n                    <jats:sup>11<\/jats:sup>\n                    C]( R)-Rolipram binding was measured by PET in LI ( n\u2009=\u200911) and C57BL\/6 wild-type (WT, n\u2009=\u20099) mice. [\n                    <jats:sup>11<\/jats:sup>\n                    C]( R)-Rolipram total distribution volumes ( V\n                    <jats:sub>T<\/jats:sub>\n                    ) were calculated and corrected for plasma-free fraction ( f\n                    <jats:sub>P<\/jats:sub>\n                    ) measured in a separate group of LI ( n\u2009=\u20096) and WT ( n\u2009=\u20097) mice. PDE4 enzyme activity was measured using in\u00a0vitro samples of cerebral cortices from groups of LI ( n\u2009=\u20094), heterozygote ( n\u2009=\u20094), and WT ( n\u2009=\u20094) mice. Disc1 LI mice showed a 41% increase in V\n                    <jats:sub>T<\/jats:sub>\n                    (18\u2009\u00b1\u20096 vs. 13\u00b14\u2009mL\/cm\n                    <jats:sup>3<\/jats:sup>\n                    , P\u2009=\u20090.04) compared to WT mice. V\n                    <jats:sub>T<\/jats:sub>\n                    \/ f\n                    <jats:sub>P<\/jats:sub>\n                    showed a 73% significant increase (90\u2009\u00b1\u200931 vs. 52\u2009\u00b1\u200915\u2009mL\/cm\n                    <jats:sup>3<\/jats:sup>\n                    , P\u2009=\u20090.004) in Disc1 LI compared to WT mice. PDE4 enzymatic activity assay confirmed in\u00a0vivo findings showing significant group differences ( p\u2009&lt;\u20090.0001). In conclusion, PDE4 activity was increased in the absence of critical DISC1 protein isoforms both in\u00a0vivo and in\u00a0vitro. Additionally, [\n                    <jats:sup>11<\/jats:sup>\n                    C]( R)-Rolipram PET was sensitive enough to assess altered PDE4 activity caused by PDE4\u2013DISC1 interaction.\n                  <\/jats:p>","DOI":"10.1177\/0271678x18758997","type":"journal-article","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T05:35:03Z","timestamp":1518413703000},"page":"1306-1313","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["[\n                    <sup>11<\/sup>\n                    C](\n                    <i>R<\/i>\n                    )-Rolipram positron emission tomography detects DISC1 inhibition of phosphodiesterase type 4 in live\n                    <i>Disc1<\/i>\n                    locus-impaired mice"],"prefix":"10.1177","volume":"39","author":[{"given":"Maarten","family":"Ooms","sequence":"first","affiliation":[{"name":"Molecular Imaging Branch, NIMH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Tsujikawa","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, NIMH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talakad G","family":"Lohith","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, NIMH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanch\u00e9 N","family":"Mabins","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, NIMH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami S","family":"Zoghbi","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, NIMH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Sumitomo","sequence":"additional","affiliation":[{"name":"Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Jaaro-Peled","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Johns Hopkins University School of Medicine, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7927-9483","authenticated-orcid":false,"given":"Yasuyuki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, NIMH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Telu","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, NIMH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor W","family":"Pike","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, NIMH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Tomoda","sequence":"additional","affiliation":[{"name":"Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B","family":"Innis","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, NIMH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Sawa","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Johns Hopkins University School of Medicine, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Fujita","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, NIMH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,2,12]]},"reference":[{"key":"bibr1-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.171"},{"key":"bibr2-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5335.58"},{"key":"bibr3-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001016"},{"key":"bibr4-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2006.07.018"},{"key":"bibr5-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704743"},{"key":"bibr6-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2012.04.030"},{"key":"bibr7-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20728"},{"key":"bibr8-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1042\/bj3330139"},{"key":"bibr9-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3120"},{"key":"bibr10-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.154"},{"key":"bibr11-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85594"},{"key":"bibr12-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112915"},{"key":"bibr13-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10118"},{"key":"bibr14-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.100"},{"key":"bibr15-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.12.061"},{"key":"bibr16-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903413106"},{"key":"bibr17-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511189103"},{"key":"bibr18-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr400"},{"key":"bibr19-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1258\/la.2010.0010021"},{"key":"bibr20-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2005.03.017"},{"key":"bibr21-0271678X18758997","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.116.177949"},{"key":"bibr22-0271678X18758997","first-page":"455","volume":"46","author":"Tai 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