RRC ID |
50071
|
著者 |
Onishi T, Sakamoto H, Namiki S, Hirose K.
|
タイトル |
The Altered Supramolecular Structure of Dopamine D2 Receptors in Disc1-deficient Mice.
|
ジャーナル |
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.
|
巻・号 |
8(1)
|
ページ |
1692
|
公開日 |
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
|
引用数 |
2
|
リソース情報 |
実験動物マウス |
RBRC03709 |