title: Decreased DNA Methylation in the Shati/Nat8l Promoter in Both Patients with Schizophrenia and a Methamphetamine-Induced Murine Model of Schizophrenia-Like Phenotype.
abstract: The number of patients with schizophrenia has increased over the past decade. Previously, many studies have been performed to establish its diagnostic criteria, prophylactic methods, and effective therapies. In this study, we analyzed whether the ratios of DNA methylation in CpG islands of the Shati/Nat8l is decreased in model mice of schizophrenia-like phenotype using genomic DNA collected from brain regions and peripheral blood, since the mouse model of schizophrenia-like phenotype, mice treated repeatedly with methamphetamine showed increase of Shati/Nat8l mRNA expression in our previous experiment. The ratios of Shati/Nat8l CpG island methylation were significantly decreased in both the nucleus accumbens and the peripheral blood of model mice compared with those of control mice. We also investigated Shati/Nat8l methylation in the blood of patients with schizophrenia. We found that Shati/Nat8l CpG island methylation ratios were lower in the patients with schizophrenia than in the healthy controls, which is consistent with our findings in the mice model. To our knowledge, this is the first study to show similar alterations in methylation status of a particular genomic DNA site in both the brain and peripheral blood of mice. Furthermore, the same phenomenon was observed in corresponding human genomic sequences of the DNA extracted from the peripheral blood of patients with schizophrenia. Based on our findings, DNA methylation profiles of the CpG island of Shati/Nat8l might be a diagnostic biomarker of schizophrenia.
authors.affiliation: Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Uno
authors.affiliation: Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Yuu
authors.initials: Y
authors.lastname: Kikuchi
authors.affiliation: Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Iwata
authors.affiliation: Department of Neuropsychiatry, Kanazawa Medical University, Kahoku, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Uehara
authors.affiliation: Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.|Medical Corporation Syoufukai, Matsuoka Hospital, Oyabe, Japan.
authors.forename: Tadasu
authors.initials: T
authors.lastname: Matsuoka
authors.affiliation: Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.|Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Tomiki
authors.initials: T
authors.lastname: Sumiyoshi
authors.affiliation: Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Jinno
authors.affiliation: Department of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Takada
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Furukawa-Hibi
authors.affiliation: Advanced Diagnostic System Research Laboratory, Fujita Health University, Graduate School of Health Sciences & Aino University, Toyoake & Ibaragi, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.affiliation: Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Atsumi
authors.identifier: http://orcid.org/0000-0001-6916-9160
authors.initials: A
authors.lastname: Nitta
mesh_terms: D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics* / Q000473:pathology
chemical_list: D008694:Methamphetamine; D000123:Acetyltransferases; C000611572:NAT8L protein, human