Decreased DNA methylation in the Shati/Nat8l promoter in both patients with schizophrenia and a methamphetamine-induced Murine model of schizophrenia-like phenotype

Kyosuke Uno, Yuu Kikuchi, Mina Iwata, Takashi Uehara, Tadasu Matsuoka, Tomiki Sumiyoshi, Yoshinori Okamoto, Hideto Jinno, Tatsuyuki Takada, Yoko Furukawa-Hibi, Toshitaka Nabeshima, Yoshiaki Miyamoto, Atsumi Nitta

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Article numbere0157959
JournalPLoS One
Volume11
Issue number6
DOIs
Publication statusPublished - 01-06-2016

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Methamphetamine
DNA methylation
DNA Methylation
CpG Islands
Methylation
Schizophrenia
Blood
animal models
promoter regions
Phenotype
phenotype
methylation
blood
DNA
Brain
genomics
mice
Biomarkers
brain
Nucleus Accumbens

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Uno, Kyosuke ; Kikuchi, Yuu ; Iwata, Mina ; Uehara, Takashi ; Matsuoka, Tadasu ; Sumiyoshi, Tomiki ; Okamoto, Yoshinori ; Jinno, Hideto ; Takada, Tatsuyuki ; Furukawa-Hibi, Yoko ; Nabeshima, Toshitaka ; Miyamoto, Yoshiaki ; Nitta, Atsumi. / Decreased DNA methylation in the Shati/Nat8l promoter in both patients with schizophrenia and a methamphetamine-induced Murine model of schizophrenia-like phenotype. In: PLoS One. 2016 ; Vol. 11, No. 6.
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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.",
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Uno, K, Kikuchi, Y, Iwata, M, Uehara, T, Matsuoka, T, Sumiyoshi, T, Okamoto, Y, Jinno, H, Takada, T, Furukawa-Hibi, Y, Nabeshima, T, Miyamoto, Y & Nitta, A 2016, 'Decreased DNA methylation in the Shati/Nat8l promoter in both patients with schizophrenia and a methamphetamine-induced Murine model of schizophrenia-like phenotype', PLoS One, vol. 11, no. 6, e0157959. https://doi.org/10.1371/journal.pone.0157959

Decreased DNA methylation in the Shati/Nat8l promoter in both patients with schizophrenia and a methamphetamine-induced Murine model of schizophrenia-like phenotype. / Uno, Kyosuke; Kikuchi, Yuu; Iwata, Mina; Uehara, Takashi; Matsuoka, Tadasu; Sumiyoshi, Tomiki; Okamoto, Yoshinori; Jinno, Hideto; Takada, Tatsuyuki; Furukawa-Hibi, Yoko; Nabeshima, Toshitaka; Miyamoto, Yoshiaki; Nitta, Atsumi.

In: PLoS One, Vol. 11, No. 6, e0157959, 01.06.2016.

Research output: Contribution to journalArticle

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AU - Uno, Kyosuke

AU - Kikuchi, Yuu

AU - Iwata, Mina

AU - Uehara, Takashi

AU - Matsuoka, Tadasu

AU - Sumiyoshi, Tomiki

AU - Okamoto, Yoshinori

AU - Jinno, Hideto

AU - Takada, Tatsuyuki

AU - Furukawa-Hibi, Yoko

AU - Nabeshima, Toshitaka

AU - Miyamoto, Yoshiaki

AU - Nitta, Atsumi

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N2 - 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.

AB - 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.

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