|
Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >
Changes in subunit composition of NMDA receptors in animal models of schizophrenia by repeated administration of methamphetamine
This item is licensed under:Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
| Title: | Changes in subunit composition of NMDA receptors in animal models of schizophrenia by repeated administration of methamphetamine |
| Authors: | Oka, Matsuhiko Browse this author | | Ito, Koki Browse this author →KAKEN DB | | Koga, Minori Browse this author →KAKEN DB | | Kusumi, Ichiro Browse this author →KAKEN DB |
| Keywords: | Schizophrenia | | NMDA receptor | | GluN1 | | Animal model | | Methamphetamine |
| Issue Date: | 20-Dec-2020 |
| Publisher: | Elsevier |
| Journal Title: | Progress in neuro-psychopharmacology & biological psychiatry |
| Volume: | 103 |
| Start Page: | 109984 |
| Publisher DOI: | 10.1016/j.pnpbp.2020.109984 |
| Abstract: | The dopamine and glutamate hypotheses reflect only some of the pathophysiological changes associated withschizophrenia. We have proposed a new“comprehensive progressive pathophysiology model”based on the“dopamine to glutamate hypothesis.”Repeated administration of methamphetamine (METH) at a dose of2.5 mg/kg in rats has been used to assess dynamic changes in the pathophysiology of schizophrenia. Previous useof this model suggestedN-methyl-D-aspartate receptor (NMDA-R) dysfunction, but the mechanism could only beinferred from limited, indirect observations. In the present study, we used this model to investigate changes inthe expression of NMDA-R subunits. Repeated administration of METH significantly decreased the gene ex-pression levels of glutamate ionotropic receptor NMDA type subunit (Grin) subtypesGrin1andGrin2cin theprefrontal cortex (PFC),Grin1andGrin2ain the hippocampus (HPC), andGrin1,Grin2b, andGrin2din thestriatum (ST).We observed a significant difference inGrin1expression between the PFC and ST. Furthermore,repeated administration of METH significantly decreased the protein expression of GluN1 in both cytosolic andsynaptosomal fractions isolated from the PFC, and significantly decreased the protein expression of GluN1 in thecytosolic fraction, but not the synaptosomal fraction from the ST. These regional differences may be due tovariations in the synthesis of GluN1 or intracellular trafficking events in each area of the brain. Considering thatknockdown ofGrin1in mice affects vulnerability to develop schizophrenia, these results suggest that this modelreflects some of the pathophysiological changes of schizophrenia, combining both the dopamine and glutamatehypotheses. |
| Rights: | © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/83602 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 久住 一郎
|
