Investigation of the epigenetics at schizophrenia pathology

• Project/Area Number: 25860108
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: University of Toyama
• Principal Investigator: UNO Kyosuke 富山大学, 大学院医学薬学研究部(薬学), 助教 (30608774)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 統合失調症 / エピジェネティクス / メチル化

Outline of Final Research Achievements

We have identified Shati and the regulation system of Shati is expected as therapeutic or diagnostic tools. In this study, we focused DNA methylation. To analyze the DNA methylation, mice were treated with METH or saline. Mice genomic DNA was extracted from NAc tissue and peripheral blood followed by bisulfite treatment. In METH treated mice, the methylation level of Shati promoter specific region prepared from NAc was lower than that of saline treated mice. Moreover, same domain from peripheral blood in METH treated mice was less methylated compared with saline treated mice. Furthermore, the methylation level of the specific region of SHATI obtained from peripheral blood of schizophrenia subjects were significantly lower than that of healthy subjects.
These results indicate that expression of Shati might be regulated by DNA methylation, and to analyze the blood level of methylation at Shati specific genomic region could help a diagnosis of psychiatric disorders in clinical field.

Research Products

• [Journal Article] The Piccolo Intronic Single Nucleotide Polymorphism rs13438494 Regulates Dopamine and Serotonin Uptake and Shows Associations with Dependence-like Behavior in Genomic Association Study. (2015)
  • Author(s): Uno K, Nishizawa D, Seo S, Takayama K, Matsumura S, Sakai N, Ohi K, Nabeshima T, Hashimoto R, Ozaki N, Hasegawa J, Sato N, Tanioka F, Sugimura H, Fukuda K, Higuchi S, Ujike H, Inada T, Iwata N, Sora I, Iyo M, Kondo N, Won MJ, Naruse N, Uehara-Aoyama K, Itokawa M, Yamada M, Ikeda K, Miyamoto Y, Nitta A
  • Journal Title: Curr Mol Med. Volume: 15
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Overexpression of Shati/Nat8l, an N-acetyltransferase, in the nucleus accumbens attenuates the response to methamphetamine via activation of group II mGluRs in mice (2014)
  • Author(s): Miyamoto Y., Ishikawa Y., Iegaki N., Sumi K., Fu K., Sato K., Furukawa-Hibi Y., Muramatsu S., Nabeshima T., Uno K., Nitta A.
  • Journal Title: Int. J. Neuropsychopharmacol. Volume: 17 Issue: 08 Pages: 1-12
  • DOI: 10.1017/s146114571400011x
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of Shati/Nat8l, an N-acetyltransferase, in the nucleus accumbens attenuates the response to methamphetamine via activation of group II mGluRs in mice. (2014)
  • Author(s): Yoshiaki Miyamoto, Yudai Ishikawa, Noriyuki Iegaki, Kazuyuki Sumi, Kequan Fu, Keiji Sato, Yoko Furukawa-Hibi, Shin-ichi Muramatsu, Toshitaka Nabeshima, Kyosuke Uno and Atsumi Nitta.
  • Journal Title: Int J Neuropsychopharmacol. Volume: 24 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Functional analysis of deep intronic SNP rs13438494 in intron 24 of PCLO gene (2013)
  • Author(s): Seo S, Takayama K, Uno K, Ohi K, Hashimoto R, Nishizawa D, Ikeda K, Ozaki N, Nabeshima T, Miyamoto Y, Nitta A
  • Journal Title: PLoS ONE Volume: 8(10) Issue: 10 Pages: e76960-e76960
  • DOI: 10.1371/journal.pone.0076960
  • Peer Reviewed
• [Journal Article] N-acetyltransferase 8-like accelerates lipid turnover and increases energy expenditure in brown adipocytes. (2013)
  • Author(s): Ariane R. Pessentheiner, Helmut J. Pelzmann, Evelyn Walenta, Martina Schweiger, Lukas N. Groschner, Wolfgang F. Graier, Dagmar Kolb, Kyosuke Uno, Toh Miyazaki, Atsumi Nitta, Dietmar Rieder, Andreas Prokesch, and Juliane G. Bogner-Strauss.
  • Journal Title: J Biol Chem. Volume: 288(50) Issue: 50 Pages: 36040-36051
  • DOI: 10.1074/jbc.m113.491324
  • Peer Reviewed
• [Presentation] メタンフェタミンはドパミンD１受容体シグナルの活性化によってShati/Nat8lを上方制御する. (2015)
  • Author(s): 宮﨑杜夫、宇野恭介、菊池佑、日比陽子、鍋島俊隆、宮本嘉明、新田淳美.
  • Organizer: 日本薬理学会第88回年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] マウス海馬におけるShati/Nat8l過剰発現は長期増強を増加させる. (2015)
  • Author(s): 加冶甚一郎, 宮本嘉明, 佐藤慶治, 日比陽子, 村松慎一, 鍋島俊隆, 宇野恭介, 新田淳美
  • Organizer: 日本薬理学会第88回年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] N-Acettyltransferase Shati/Nat8l in the dorsal striatum regulates sociability and motivation via control of the serotonergic neuronal system in mice. (2014)
  • Author(s): Nitta A, Iegaki N, Ishikawa Y, Sumi K, Furukawa-Hibi Y, Muramatsu S, Nabeshima T, Uno K, Miyamoto Y.
  • Organizer: ACNP 53rd annual meeting
  • Place of Presentation: フェニックス アメリカ
  • Year and Date: 2014-12-07 – 2014-12-11
• [Presentation] メタンフェタミンを連続投与したマウスの側坐核と血液では精神疾患関連遺伝子Shati/Nat8lのDNAメチル化の割合が低下している. (2014)
  • Author(s): 菊地佑, 宇野恭介, 宮崎杜生, 徐承姫, 岩田美奈, 宮本嘉明, 新田淳美
  • Organizer: 日本薬学会北陸支部第１25回例会
  • Place of Presentation: 金沢
  • Year and Date: 2014-11-16
• [Presentation] Shati/Nat8l regulates dopamine release-induced by nicotine in nucleus accumbens (2014)
  • Author(s): Uno K, Miyamoto Y, Nitta A.
  • Organizer: 16th International Society of Addiction Medicine Annual Meeting
  • Place of Presentation: 横浜
  • Year and Date: 2014-10-02 – 2014-10-06
  • Invited
• [Presentation] マウス側坐核のTMEM168過剰発現は不安および感覚運動制御障害を引き起こす (2014)
  • Author(s): Kequan Fu, 宮本嘉明, 斎鹿絵里子, 鷲見和之, 村松慎一, 宇野恭介, 新田淳美
  • Organizer: 第57回日本神経化学会（奈良）大会
  • Place of Presentation: 奈良
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] マウス前頭前皮質におけるPiccoloノックダウンは、シナプス神経伝達を障害する (2014)
  • Author(s): 稲垣良, 宮本嘉明, 村松慎一, 鷲見和之, 鍋島俊隆, 宇野恭介, 新田淳美
  • Organizer: 第65回日本薬理学会北部
  • Place of Presentation: 福島
  • Year and Date: 2014-09-26 – 2014-09-27
• [Presentation] PCLO SNP rs13438494 regulates DA and 5-HT uptake, accompanied with splicing efficiency and dependence-like behaviors in genomic association studies. (2014)
  • Author(s): Uno K., Nishizawa D., Seo S., Sakai N., Ohi K., Nabeshima T., Hashimoto R., Ozaki N., Ikeda K., Miyamoto Y., Nitta A
  • Organizer: The 29th CINP World Congress of Neuropsycchopharmacology
  • Place of Presentation: バンクーバー カナダ
  • Year and Date: 2014-06-22 – 2014-06-26
• [Presentation] Effects of pseudoginsenoside-F11 on methamphetamine-induced behaviors related to the dopaminergic and GABAergic neuronal system in the nucleus accumbens. (2014)
  • Author(s): Nitta A., Lin H., Fu K., Wu C., Yang J., Uno K., Miyamoto Y.
  • Organizer: The 29th CINP World Congress of Neuropsycchopharmacology
  • Place of Presentation: バンクーバー カナダ
  • Year and Date: 2014-06-22 – 2014-06-26
• [Presentation] Depression-like behaviors were induced by overexpression of Shati/Nat8l, an N-acetyltransferase, in the striatum of mice. (2014)
  • Author(s): Miyamoto Y., Iegaki N., Sumi K., Ishikawa Y., Furuta T., Furukawa-Hib Y., Muramatsu S., Nabeshima T., Uno K., Nitta A.
  • Organizer: The 29th CINP World Congress of Neuropsycchopharmacology
  • Place of Presentation: バンクーバー カナダ
  • Year and Date: 2014-06-22 – 2014-06-26
• [Presentation] マウス側坐核でのShati/Nat8lの過剰発現はニコチン誘発性ドパミン遊離量を変化させる. (2014)
  • Author(s): 宇野恭介, 高岡和也, 村松慎一, 鍋島俊隆, 宮本嘉明, 新田淳美.
  • Organizer: 日本薬学会第134回年会
  • Place of Presentation: 熊本
• [Presentation] マウスにおけるShati/Nat8l転写開始点上流のメチル化の減少はメタンフェタミンの連続投与によって誘導される. (2014)
  • Author(s): 宮﨑杜夫, 宇野恭介, 菊池佑, 日比陽子, 鍋島俊隆, 宮本嘉明, 新田淳美.
  • Organizer: 第87回日本理薬学会年会
  • Place of Presentation: 仙台
• [Presentation] マウスにおけるうつ様行動に対するサイシンの効果 (2014)
  • Author(s): 佐藤慶治, 宇野恭介, 笹谷晴枝, 宮本嘉明, 門田重利, 新田淳美.
  • Organizer: 第87回日本薬学会年会
  • Place of Presentation: 仙台
• [Presentation] iccoloのSNPであるrs13438494は遺伝子関連解析において依存性関連疾患と関連がありドパミンおよびセロトニンの取り込みを制御する (2014)
  • Author(s): 宇野恭介, 西澤大輔, 除承姫, 高山佳奈子, 松村祥平, 酒井規雄, 大井一高, 鍋島俊隆, 橋本亮太, 尾崎紀夫 池田和隆, 宮本嘉明, 新田淳美.
  • Organizer: 第87回日本薬学会年会
  • Place of Presentation: 仙台
• [Presentation] The role of shati/nat8l in the addicted mice brain. (2013)
  • Author(s): Nitta A, Ishikawa Y, Sumi K, Iegaki N, Furukawa-Hibi Y, Muramatsu S, Nabeshima T, Uno K, Miyamoto Y.
  • Organizer: World Congress of Pharmacy and Pharmaceutical Sciences 2013; 73rd International Congress of FIP.
  • Place of Presentation: Dublin
• [Presentation] PCLO SNP regulates DA and 5-HT uptake in their transporter over expressed PC12 or HEK293 cells. (2013)
  • Author(s): Kyosuke Uno, Kanako Takayama, Seunghee Seo, Kazutaka Ohi, Ryota Hashimoto, Daisuke Nishizawa, Kazutaka Ikeda, Norio Sakai, Toshitaka Nabeshima, Yoshiaki Miyamoto, Atsumi Nitta.
  • Organizer: The 6th MCCS-Asia Symposium‐Joint International Symposium
  • Place of Presentation: Kyoto
• [Presentation] shati/nat8l and NAA increases with the development in mice. (2013)
  • Author(s): Kazuyuki Sumi, Kyosuke Uno, Ryo Iwamoto, Toshitaka Nabeshima, Yoko Furukawa-Hibi, Yoshiaki Miyamoto, Atsumi Nitta.
  • Organizer: The 6th MCCS-Asia Symposium‐Joint International Symposium
  • Place of Presentation: Kyoto
• [Presentation] 培養マウス神経細胞における精神疾患関連遺伝子Shati/Nat8lの細胞内機能についての研究 (2013)
  • Author(s): 松村祥平, 宇野恭介, 日比陽子, 村松慎一, 鍋島俊隆, 宮本嘉明, 新田淳美.
  • Organizer: 日本薬学会北陸支部第１２５回例会
  • Place of Presentation: 金沢
• [Presentation] マウス前頭前皮質におけるpiccoloノックダウンは情動および認知機能に影響を与える. (2013)
  • Author(s): 稲垣良, 宮本嘉明, 村松慎一, 鍋島俊隆, 宇野恭介, 新田淳美
  • Organizer: 第23回日本臨床精神神経薬理学会・第43回日本神経精神薬理学会合同年会
  • Place of Presentation: 沖縄
• [Presentation] 精神疾患に関連するPCLO SNP rs13438494の分子生物学的検討 (2013)
  • Author(s): 宇野恭介, 徐承姫, 松村祥平, 大井一高, 橋本亮太, 西澤大輔, 池田和隆, 酒井規雄, 鍋島俊隆, 宮本嘉明, 新田淳美
  • Organizer: 精神疾患に関連するPCLO SNP rs13438494の分子生物学的検討
  • Place of Presentation: 沖縄
• [Presentation] マウス側坐核Shati/Nat8l過剰発現はニコチンによる側坐核からのドパミン遊離量の変化に影響する. (2013)
  • Author(s): 高岡和也, 宇野恭介, 鷲見和之, 村松慎一, 鍋島俊隆, 宮本嘉明, 新田淳美
  • Organizer: 平成25年度アルコール・薬物依存関連学会合同学術集会
  • Place of Presentation: 岡山
• [Presentation] マウス前頭前皮質におけるShati/Nat8lの神経機能解析 (2013)
  • Author(s): 鷲見和之, 宇野恭介, 宮本嘉明, 岩本諒, 鍋島俊隆, 古川-日比陽子, 新田淳美
  • Organizer: 日本薬理学会北部会
  • Place of Presentation: 旭川
• [Presentation] マウス線条体でのShati/Nat8l過剰発現は妊娠期ストレスへの感受性および産褥期におけるうつ様行動を誘導する (2013)
  • Author(s): 高岡和也, 宇野恭介, 村松慎一, 鍋島俊隆, 宮本嘉明, 新田淳美
  • Organizer: 第21回クリニカルファーマシーシンポジウム・医療薬学フォーラム2013
  • Place of Presentation: 金沢
• [Presentation] セロトニンおよびドパミントランスポーターを過剰発現させたPC12およびHEK293細胞において, PCLOのSNPはモノアミン取り込みを制御する (2013)
  • Author(s): 宇野恭介, 高山佳奈子, 徐承姫, 大井一高, 橋本亮太, 西澤大輔, 池田和隆, 酒井規雄, 鍋島俊隆, 宮本嘉明, 新田淳美.
  • Organizer: Neuro 2013
  • Place of Presentation: 京都
• [Patent(Industrial Property Rights)] 危険ドラッグの検出用細胞および検出方法 (2015)
  • Inventor(s): 新田淳美 宇野恭介 宮崎杜生
  • Industrial Property Rights Holder: 新田淳美 宇野恭介 宮崎杜生
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-030116
  • Filing Date: 2015-02-19
• [Patent(Industrial Property Rights)] 精神障害の検査方法および検査キット (2014)
  • Inventor(s): 新田淳美 宇野恭介
  • Industrial Property Rights Holder: 国立大学法人富山大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-02-18
  • Overseas