title: Effects of repeated dizocilpine treatment on glutamatergic activity in the prefrontal cortex in an animal model of schizophrenia: An in vivo proton magnetic resonance spectroscopy study at 9.4T.
abstract: Repeated exposure to dizocilpine (MK-801) can be used as a model of schizophrenia that incorporates disease progression. Proton magnetic resonance spectroscopy (1H MRS) has been widely used to investigate schizophrenia-related alterations in glutamate (Glu). The purpose of this study was to investigate metabolic alterations in the prefrontal cortex (PFC) in an animal model of schizophrenia by using in vivo1H MRS. Because of the spectral overlap of Glu and glutamine (Gln), high-field1H MRS with short echo time (TE) was used. A point-resolved spectroscopy sequence was used to measure the levels of Glu and Gln, and the brain metabolites in a volume of interest (22.5μL) located in the PFC region of rats (n=13) before and after 6days of MK-801 (0.5mg/kg) treatment. Analysis of the spectra showed that the cross-contamination of Glu and Gln can be considered to comparably low. No metabolic parameters were altered (p>0.05). However, differences in Glu and N-acetylaspartate (NAA) levels between two times were significantly correlated (p<0.01). The results showed both decreased (in 6 of the 13 rats) and increased (7 of the 13 rats) levels of Glu and NAA, which suggested that these opposite metabolic alterations reflect two stage of disease progression. The results suggest that high-field and short TE in vivo1H MRS can quantify Glu and Gln with reliably low level of cross-contamination and that repeated exposure to MK-801 induces the progressive development of schizophrenia.
authors.affiliation: Department of Biomedical Engineering, Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Chi-Hyeon
authors.initials: CH
authors.lastname: Yoo
authors.affiliation: Department of Biomedical Engineering, Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea.
authors.forename: Kyu-Ho
authors.initials: KH
authors.lastname: Song
authors.affiliation: Department of Biomedical Engineering, Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Song-I
authors.initials: SI
authors.lastname: Lim
authors.affiliation: Ehwa Brain Institute, Ehwa Womans University, Seoul, Republic of Korea.
authors.forename: Do-Wan
authors.initials: DW
authors.lastname: Lee
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Dong-Cheol
authors.initials: DC
authors.lastname: Woo
authors.affiliation: Department of Biomedical Engineering, Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea. Electronic address: bychoe@catholic.ac.kr.
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Choe
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D018698:Glutamic Acid; D016291:Dizocilpine Maleate
keywords: Dizocilpine (MK-801); Glutamatergic activity; In vivo proton magnetic resonance spectroscopy ((1)H MRS); Schizophrenia