RIKEN BRAIN SCIENCE INSTITUTE (理研BSI)

Faculty Detail / 研究室詳細

精神疾患動態研究チーム

シニア・チームリーダー

Bipolar disorder, Mitochondria, Epigenetics

加藤  忠史

研究内容

私たちは、双極性障害(躁うつ病)の原因を解明し、診断法・治療法を開発することを目指して研究を進めています。これまでの研究から、ミトコンドリア機能障害が双極性障害の原因の一つであると考え、モデル動物の解析、患者脳組織の解析、ゲノム解析などを行っています。今後、双極性障害を引き起こしている脳の病理学的変化を特定することを目指していきます。また、精神疾患の病態にエピジェネティクス要因が関与する可能性が示唆されています。患者死後脳および動物モデルの解析から、精神疾患の病態におけるエピジェネティクスの意義について検討を進めます。

躁うつ病モデルマウスに対するリチウムの効果
横軸は時間(48時間)、縦軸が輪回し行動量を示す。周期的に行動量が多くなっていたマウスにリチウムを投与したところ、行動量の波が収まりました。

主な発表論文 全て表示する

  1. 1

    Takata A*, Matsumoto N, and Kato T* (* co-corresponding authors): "Genome-wide identification of splicing QTLs in the human brain and their enrichment among schizophrenia-associated loci", Nature Communications, 8, 14519 (2017)

  2. 2

    Kataoka M*, Matoba N*, Sawada T, Kazuno AA, Ishiwata M, Fujii K, Matsuo K, Takata A+, Kato T+ (*co-first authors in alphabetical order, and + co-corresponding authors): "Exome sequencing for bipolar disorder points to roles of de novo loss-of-function and protein-altering mutations", Molecular Psychiatry, 21(7), 885-93 (2016)

  3. 3

    Kasahara T*, Takata A*, Kato TM*, Kubota-Sakashita M, Sawada T, Kakita A, Mizukami H, Kaneda D, Ozawa K, and Kato T(*co-first authors) : "Depression-like Episodes in Mice Harboring mtDNA Deletions in Paraventricular Thalamus", Molecular Psychiatry, , 21, 39-48 (2015)

  4. 4

    Bundo M, Toyoshima M, Okada Y, Akamatsu W, Ueda J, Nemoto-Miyauchi T, Sunaga F, Toritsuka M, Ikawa D, Kakita A, Kato M, Kasai K, Kishimoto T, Nawa H, Okano H, Yoshikawa T, Kato T, and Iwamoto K: "Increased L1 Retrotransposition in the Neuronal Genome in Schizophrenia.", Neuron, 81(2), 306-13 (2014)

  5. 5

    Iwamoto K, Bundo M, Ueda J, Oldham MC, Ukai W, Hashimoto E, Saito T, Geschwind DH, and Kato T: "Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons.", Genome Res, 21(5), 688-96 (2011)

  6. 6

    Kubota M, Kasahara T, Iwamoto K, Komori A, Ishiwata M, Miyauchi T, and Kato T: "Therapeutic implications of down-regulation of cyclophilin D in bipolar disorder.", Int J Neuropsychopharmacol, 13(10), 1355-68 (2010)

  7. 7

    Kasahara T, Abe K, Mekada K, Yoshiki A, and Kato T: "Genetic variation of melatonin productivity in laboratory mice under domestication.", Proc Natl Acad Sci U S A, 107(14), 6412-7 (2010)

  8. 8

    Oldham MC, Konopka G, Iwamoto K, Langfelder P, Kato T, Horvath S, and Geschwind DH: "Functional organization of the transcriptome in human brain.", Nat Neurosci, 11(11), 1271-82 (2008)

  9. 9

    Kato T: "Molecular neurobiology of bipolar disorder: a disease of 'mood-stabilizing neurons'?", Trends Neurosci, 31(10), 495-503 (2008)

  10. 10

    Kuratomi G., Iwamoto K., Bundo M., Kusumi I., Kato N., Iwata N., Ozaki N., and Kato T.: "Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins.", Molecular Psychiatry, 13, 429-441 (2008)

  11. 11

    Kubota M, Kasahara T, Nakamura T, Ishiwata M, Miyauchi T, and Kato T: "Abnormal Ca2+ dynamics in transgenic mice with neuron-specific mitochondrial DNA defects.", J Neurosci, 26(47), 12314-24 (2006)

  12. 12

    Kasahara T, Kubota M, Miyauchi T, Noda Y, Mouri A, Nabeshima T, and Kato T.: "Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes.", Mol Psychiatry, 11(6), 577-93 (2006)

  13. 13

    Iwamoto K, Bundo M, and Kato T: "Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis.", Hum Mol Genet, 14(2), 241-53 (2005)

  14. 14

    Kakiuchi C, Iwamoto K, Ishiwata M, Bundo M, Kasahara T, Kusumi I, Tsujita T, Okazaki Y, Nanko S, Kunugi H, Sasaki T, and Kato T: "Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder.", Nat Genet, 35(2), 171-5 (2003)

プレスリリース 全て表示する