RRC ID 50071
Author Onishi T, Sakamoto H, Namiki S, Hirose K.
Title The Altered Supramolecular Structure of Dopamine D2 Receptors in Disc1-deficient Mice.
Journal Sci Rep
Abstract Disc1 is a susceptibility gene for psychiatric disorders including schizophrenia. It has been suggested that excess transmission through dopamine type 2 receptors (D2Rs) in the striatum is an underlying mechanism of pathogenesis. In this study, we used super-resolution microscopy to study the distribution of D2Rs at the nanoscale in mice lacking exons 2 and 3 of Disc1 (Disc1-deficient mice). We found that D2Rs in the nucleus accumbens (NAc) of wild-type mice form nanoclusters (~ 20,000 nm2), and that Disc1-deficient mice have larger and more D2R nanoclusters than wild-type mice. Interestingly, administration of clozapine reduced the size and spatial distribution of the nanoclusters only in Disc1-deficient mice. Moreover, we observed that medium spiny neurons in the NAc of Disc1-deficient mice had reduced spine density on their dendrites than did wild-type mice, and this was also reversed by clozapine administration. The altered D2R nanoclusters might be morphological representations of the altered dopaminergic transmission in disease states such as schizophrenia.
Volume 8(1)
Pages 1692
Published 2018-1-26
DOI 10.1038/s41598-018-20090-0
PII 10.1038/s41598-018-20090-0
PMID 29374282
PMC PMC5785963
MeSH Animals Mice Microscopy, Fluorescence Nerve Tissue Proteins / deficiency* Nucleus Accumbens / pathology* Protein Conformation Protein Multimerization* Receptors, Dopamine D2 / chemistry* Receptors, Dopamine D2 / metabolism*
IF 3.998
Times Cited 2
Mice RBRC03709