Changes in subunit composition of NMDA receptors in animal models of schizophrenia by repeated administration of methamphetamine

Oka, Matsuhiko; Ito, Koki; Koga, Minori; Kusumi, Ichiro

Changes in subunit composition of NMDA receptors in animal models of schizophrenia by repeated administration of methamphetamine

Oka, Matsuhiko; Ito, Koki; Koga, Minori et al.

Progress in neuro-psychopharmacology & biological psychiatry, 2020, 103, 109984

Permalink : https://hdl.handle.net/2115/83602

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アクセス権	open access
URI	https://hdl.handle.net/2115/83602
タイトル	Changes in subunit composition of NMDA receptors in animal models of schizophrenia by repeated administration of methamphetamine
著者	Oka, Matsuhiko ; Ito, Koki ; Koga, Minori ; Kusumi, Ichiro
著者名 Oka, Matsuhiko
e-Rad_Researcher 40455663 著者名 Ito, Koki
e-Rad_Researcher 70744936 著者名 Koga, Minori
e-Rad_Researcher 30250426 著者名 Kusumi, Ichiro
言語	英語
キーワード	Schizophrenia
	NMDA receptor
	GluN1
	Animal model
	Methamphetamine
発行日	2020-12-20
出版者	Elsevier
収録物名	Progress in neuro-psychopharmacology & biological psychiatry
巻(号)	103
ページ	109984
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 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/
PISSN	0278-5846
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.pnpbp.2020.109984