biostudies-literatureOoms MIntramural NIH HHSNCRR NIH HHSNIMH NIH HHS1306-1313https://www.ebi.ac.uk/biostudies/studies/S-EPMC6668514biostudies-literatureUnknown39(7)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 vivo and in vitro. [11C](R)-Rolipram binding was measured by PET in LI (n = 11) and C57BL/6 wild-type (WT, n = 9) mice. [11C](R)-Rolipram total distribution volumes (VT) were calculated and corrected for plasma-free fraction (fP) measured in a separate group of LI (n = 6) and WT (n = 7) mice. PDE4 enzyme activity was measured using in vitro samples of cerebral cortices from groups of LI (n = 4), heterozygote (n = 4), and WT (n = 4) mice. Disc1 LI mice showed a 41% increase in VT (18 ± 6 vs. 13±4 mL/cm3, P = 0.04) compared to WT mice. VT/fP Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism[11C](R)-Rolipram positron emission tomography detects DISC1 inhibition of phosphodiesterase type 4 in live Disc1 locus-impaired mice.PMC6668514ZIA MH002795P50 MH094268ZIA MH002793R01 MH105660P41 RR001192Lohith TGJaaro-Peled HMabins SNKimura YFujita MZoghbi SSInnis RBSawa AOoms MTomoda TTelu STsujikawa TSumitomo APike VWfalse[11C](R)-Rolipram positron emission tomography detects DISC1 inhibition of phosphodiesterase type 4 in live Disc1 locus-impaired mice.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 vivo and in vitro. [11C](R)-Rolipram binding was measured by PET in LI (n = 11) and C57BL/6 wild-type (WT, n = 9) mice. [11C](R)-Rolipram total distribution volumes (VT) were calculated and corrected for plasma-free fraction (fP) measured in a separate group of LI (n = 6) and WT (n = 7) mice. PDE4 enzyme activity was measured using in vitro samples of cerebral cortices from groups of LI (n = 4), heterozygote (n = 4), and WT (n = 4) mice. Disc1 LI mice showed a 41% increase in VT (18 ± 6 vs. 13±4 mL/cm3, P = 0.04) compared to WT mice. VT/fP 2019-01-01T00:00:00Z2019 Jul2025-04-04T13:33:05.552Z2025-04-04T13:33:05.552ZS-EPMC66685142943099510.1177/0271678x1875899710.1177/0271678X18758997