%0 Journal Article
%T [11C](R)
%A Akiko Sumitomo
%A Akira Sawa
%A Hanna Jaaro-Peled
%A Maarten Ooms
%A Masahiro Fujita
%A Robert B Innis
%A Sami S Zoghbi
%A Sanch¨¦ N Mabins
%A Sanjay Telu
%A Talakad G Lohith
%A Tetsuya Tsujikawa
%A Toshifumi Tomoda
%A Victor W Pike
%A Yasuyuki Kimura
%J Journal of Cerebral Blood Flow & Metabolism
%@ 1559-7016
%D 2019
%R 10.1177/0271678X18758997
%X 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£¿¡À£¿6 vs. 13¡À4£¿mL/cm3, P£¿=£¿0.04) compared to WT mice. VT/fP showed a 73% significant increase (90£¿¡À£¿31 vs. 52£¿¡À£¿15£¿mL/cm3, P£¿=£¿0.004) in Disc1 LI compared to WT mice. PDE4 enzymatic activity assay confirmed in vivo findings showing significant group differences (p£¿<£¿0.0001). In conclusion, PDE4 activity was increased in the absence of critical DISC1 protein isoforms both in vivo and in vitro. Additionally, [11C](R)-Rolipram PET was sensitive enough to assess altered PDE4 activity caused by PDE4¨CDISC1 interaction
%K Positron emission tomography
%K phosphodiesterase 4
%K disrupted in schizophrenia
%K locus impairment mouse model
%K [11C](R)-Rolipram
%U https://journals.sagepub.com/doi/full/10.1177/0271678X18758997