Identification of mitochondrial DNA mutations in patients exhibiting neuropsychiatric symptoms

• Project/Area Number: 19591365
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kagoshima University
• Principal Investigator: NAKAMURA Masayuki Kagoshima University, 医学部・歯学部附属病院, 講師 (90332832)
• Co-Investigator(Kenkyū-buntansha): SANO Akira 鹿児島大学, 大学院・医歯学総合研究科, 教授 (30178800)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 統合失調症 / 気分障害 / 認知症 / ミトコンドリア遺伝子 / 有棘赤血球舞踏病

Research Abstract

幻覚や妄想もしくは気分の落ち込みや興味関心の喪失などの精神症状を呈し、手足の筋力低下やまぶたが下がってくるなどの筋症状を有する患者に遭遇した。このような筋症状はミトコンドリア異常を示唆するものであり、ミトコンドリア遺伝子解析を行った。その結果、これらの患者にはミトコンドリア遺伝子の一部が欠落する変異が存在することが解り、統合失調症やうつなどの精神疾患とミトコンドリア機能異常の関連が示唆された。

Research Products

• [Journal Article] Gene expression and association analyses of the PDE4B (Phosphodiesterase 4B) gene in major depressive disorder in the Japanese Population. (2008)
  • Author(s): Numata S, Iga JI, Nakataki M, Tayoshi S, Taniguchi K, Sumitani S, Tomotake M, Takahashi T, Itakura M, Kamegaya Y, Tatsumi M, Sano A, Asada T, Kunugi H, Ueno SI, Ohmori T
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet (in press)
  • Peer Reviewed
• [Journal Article] Positive association of the PDE4B (phosphodiesterase 4B) gene with schizophrenia in the Japanese population. (2008)
  • Author(s): Numata S, Ueno SI, Iga JI, Song H, Nakataki M, Tayoshi S, Sumitani S, Tomotake M, Itakura M, Sano A, Ohmori T
  • Journal Title: J Psychiatr Res 43 Pages: 7-12
  • Peer Reviewed
• [Journal Article] Microarray comparative genomic hybridization analysis of 59 patients with schizophrenia. (2008)
  • Author(s): Mizuguchi T, Hashimoto R, Itokawa M, Sano A, Shimokawa O, Yoshimura Y, Harada N, Miyake N, Nishimura A, Saitsu H, Sosonkina N, Niikawa N, Kunugi H, Matsumoto N.
  • Journal Title: J Hum Genet 53 Pages: 914-919
  • NAID: 10022603067
• [Journal Article] No association between the NDE1 gene and schizophrenia in the Japanese Population. (2008)
  • Author(s): Numata N, Ueno S, Iga J, Nakataki M, Tanahashi T, Itakura M, Sano A, Ohi K, Hashimoto R, Takeda M, Ohmori T
  • Journal Title: Schizophr Res 99 Pages: 9367-9369
  • Peer Reviewed
• [Journal Article] A new phenotype of chorea-acanthocytosis with dilated cardiomyopathy and myopathy (2007)
  • Author(s): Kageyama, Y., Matsumoto, K., Ichikawa, K., Ueno, S., Ichiba, M., Nakamura, M., & Sano A
  • Journal Title: Mov. Disord (22) Pages: 1669-167
  • Peer Reviewed
• [Journal Article] Clinical and molecular genetical assessment of a chorea-acanthocytosis pedigree (2007)
  • Author(s): Ichiba, M., Nakamura, M., Kusumoto, A., Mizuno, E., Kurano, Y., Matsuda, M., Kato, M., Tomemori, Y., Muroya, S., Nakabepu, Y., Sano, A.
  • Journal Title: J Neurol. Sci. 263 Pages: 124-132
  • Peer Reviewed
• [Journal Article] A new phenotype of chorea-acanthocytosis with dilated cardiomyopathy and myopathy. (2007)
  • Author(s): Kageyama, Y., Matsumoto, K.., Ichikawa, K.., Ueno, S., Ichiba, M.., Nakamura. M.,& Sano A
  • Journal Title: Mov. Disord 22 Pages: 1669-1670
  • Peer Reviewed
• [Journal Article] Clinical and molecular genetical assessment of a chorea-acanthocytosis pedigree. (2007)
  • Author(s): chiba, M., Nakamura, M.., Kusumoto, A.., Mizuno, E.., Kurano, Y., Matsuda, M.., Kato, M., Tomemori, Y., Muroya, S., Nakabepu, Y., Sano, A.
  • Journal Title: J Neurol. Sci. 263 Pages: 124-132
  • Peer Reviewed
• [Journal Article] N-terminal proteolysis of full-length mutant huntingtin in an inducible PC12 cell model of Huntington's disease. (2007)
  • Author(s): Ratovitski, T., Nakamura, M., D'Ambola, J., Chighladze, E.., Liang, Y., Wang, W., Graham, R., Hayden, M. R., Borchelt, D. R., Hirschhorn, R. R., Ross, CA
  • Journal Title: Cell Cycle 6 Pages: 2970-2978
  • Peer Reviewed
• [Journal Article] N Parkinson's disease genetic mutations increase cell susceptibility to stress: mutant alpha-synuclein enhances H2O2-and Sin-1-induced cell death. (2007)
  • Author(s): Jiang. H., Wu, Y. C., Nakamura. M., Liang, Y., Tanaka, Y., Holmes, S., Dawson, V. L.., Dawson, T. M.., Ross, C. A., Smith, W. W.
  • Journal Title: Neurobiol. Aging.. 28 Pages: 1709-1717
  • Peer Reviewed
• [Journal Article] The Va166Met polymorphism of the brain-derived neurotrophic factor gene is associated with psychotic feature and suicidal behavior in Japanese major depressive patients. (2007)
  • Author(s): Iga, J., Ueno, S., Yamauchi, K.., Numata, S., Tayoshi-Shibuya, S., Kinouchi, S., Nakataki, M.., Song, H., Hokoishi, K.., Tanabe, H., Sano. A., Ohmori,
  • Journal Title: Am. J. Med. Genet. B. Neuropsychiatr. Genet 5 Pages: 1003-1006
  • Peer Reviewed
• [Journal Article] Expression patterns in alternative splicing forms of prosaposin mRNA in the rat facial nerve nucleus after facial nerve transection. (2007)
  • Author(s): Chen, J., Saito, S., Kobayashi, N., Sato, K., Terashita, T., Shimokawa, T., Mominoki, K., Miyawaki, K., Sano, A., Matsuda, S.
  • Journal Title: Neurosci. Res 60 Pages: 82-94
  • Peer Reviewed
• [Journal Article] Gene expression and association analysis of vascular endothelial growth factor in major depressive disorder. (2007)
  • Author(s): Iga, J., Ueno, S., Yamauchi, K., Numata, S., Tayoshi-Shibuya, S., Kinouchi, S., Nakataki, M., Song, H., Hokoishi, K., Tanabe, H., Sano, A., Ohmori T
  • Journal Title: Prog. Neuropsychopharmacol. Biol. Psychiatry 31 Pages: 658-663
  • Peer Reviewed
• [Journal Article] Distribution of prosaposin in the rat nervous system. (2007)
  • Author(s): Hosoda, Y., Miyawaki, K., Saito, S., Chen, J., Bing, X., Terashita, T., Kobayashi, N., Araki, N., Shimokawa, T., Hamada, F., Sano, A., Tanabe, H., Matsuda, S.
  • Journal Title: Cell. Tissue. Res. 330 Pages: 197-207
  • Peer Reviewed
• [Journal Article] Psychiatric Morbidity (2007)
  • Author(s): Sano, A.
  • Journal Title: Neuroacanthocytosis Neuroacanthocytosis Syndromes II, Springer, Berlin, Germany Pages: 219-223
• [Presentation] 有棘赤血球舞踏病モデルマウスの神経細胞死はアポトーシスである (2008)
  • Author(s): 松田三恵子, 中村雅之, 市場美緒, 加藤真依子, 塩川奈理, 佐野輝
  • Organizer: 第41回 精神神経系薬物治療研究報告会
  • Place of Presentation: 千里ライフサイエンスセンター(大阪府豊中市)
  • Year and Date: 2008-12-05
• [Presentation] Three cases of mental disorders with muscle weakness, external ophthalmoplegia and mitochondrial DNA deletions (2008)
  • Author(s): Kato M., Nakamura M., Ichiba M., Tomiyasu A., Shimo H., Matsuda M., Sano A.
  • Organizer: XVIth World Congress on Psychiatric Genetics
  • Place of Presentation: Osaka Japan
  • Year and Date: 2008-10-13
• [Presentation] Three cases of mental disorders with muscle weakness, external ophthalmoplegia and mitochondrial DNA deletions (2008)
  • Author(s): Kato M., Nakamura M., Ichiba M., Tomiyasu A., Shimo H., Matsuda M., Sano A.
  • Organizer: XVIth World Congress on Psychiatric Genetics
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2008-10-13
• [Presentation] Bcl-2 family proteins are involved in neuronal apoptosis in the chorea-acanthocytosis model mouse (2008)
  • Author(s): Matsuda M., Nakamura M., Ichiba M., Kato M., Shimo H., Tomiyasu A., Kono N., Uchinokura Y., Mori S., Ishizuka T., Hayashi T., and Sano A.
  • Organizer: 第51回日本神経化学会大会
  • Place of Presentation: 富山
  • Year and Date: 2008-09-12
• [Presentation] Bc1-2 family proteins are involved in neuronal apoptosis in the chorea-acanthocytosis model mouse. (2008)
  • Author(s): Matsuda M., Nakamura M., Ichiba M., Kato M., Shimo H., Tomiyasu A., Kono N., Uchinokura Y., Mori S., Ishizuka T., Hayashi T., Sano A.
  • Organizer: 第51回 日本神経化学会大会
  • Place of Presentation: 富山国際会議場(富山市)
  • Year and Date: 2008-09-12
• [Presentation] Molecular understanding of ChAc using ChAc mouse (2008)
  • Author(s): Sano A
  • Organizer: 4th International Symposium on Neuroacanthocytosis
  • Place of Presentation: London and Oxford, UK
  • Year and Date: 2008-07-02
• [Presentation] Chorein (VPS13A) state and Proteome analysis in chorea-acnthocytosis red blood cells (2008)
  • Author(s): Nakamura M., Sano A
  • Organizer: 4th International Symposium on Neuroacanthocytosis
  • Place of Presentation: London and Oxford, UK
  • Year and Date: 2008-07-02
• [Presentation] 有棘赤血球舞踏病家系における臨床および分子遺伝学的評価について (2007)
  • Author(s): 市場美緒, 中村雅之, 河野奈理, 下 洋央, 富安昭之, 加藤真依子, 松田三恵子, 佐野 輝
  • Organizer: 第15回日本精神・行動遺伝医学会
  • Place of Presentation: 国立精神・神経センター
  • Year and Date: 2007-11-17
• [Presentation] Chrein deficiency leads to increase of DARPP-32 protein exprssion. (2007)
  • Author(s): 松田三恵子, 中村雅之, 倉野 裕, 水野恵三子, 市場美緒, 加藤真依子, 揚村明日美, 佐野 輝
  • Organizer: 第50回日本神経化学大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-10
• [Presentation] うつ病を呈し慢性進行性外眼筋麻痺の筋症状や遺伝子異常を伴い、筋病理上multiple mini-coreを認めた-例 (2007)
  • Author(s): 加藤真依子, 中村雅之, 市場美緒, 揚村明日美, 松田三恵子, 畑幸宏, 伊地知 明, 今井莉香, 佐野 輝
  • Organizer: 第29回日本生物学的精神医学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-07-13
• [Presentation] うつ病を呈し慢性進行性外眼筋麻痺の筋症状や遺伝子異常を伴い、筋病理上multiple mini-coreを認めた一例 (2007)
  • Author(s): 加藤真依子, 中村雅之, 市場美緒, 揚村明日美, 松田三恵子, 畑幸宏, 伊地知 明, 今井莉香 佐野 輝
  • Organizer: 第29回日本生物学的精神医学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-07-13
• [Presentation] ミトコンドリア病の精神症状 (2007)
  • Author(s): 佐野 輝
  • Organizer: 第29回日本生物学的精神医学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-07-12
• [Book] Neuroacanthocytosis Syndromes II A Mouse Model of Chorea-acanthocytosis (2008)
  • Author(s): Nakamura M., Katoh Y., Kurano Y., Ichiba M., Matsuda M., Katoh M., Ueno S., and Sano A.
  • Publisher: Springer, Berlin, Germany
• [Book] Neuroacanthocytosis Syndromes II Psychiatric Morbidity in Neuroacanthocytosis (2008)
  • Author(s): Sano A.
  • Publisher: Springer, Berlin, Germany
• [Book] Neuroacanthocytosis Syndromes II A Mouse Model of Chorea-acanthocytosis (2008)
  • Author(s): Nakamura M., Katoh Y., Kurano Y., Ichiba M., Matsuda M., Katoh M., Ueno S., Sano A.
  • Publisher: Springer, Berlin, Germany
• [Book] Neuroacanthocytosis update, Brain Nerve (2008)
  • Author(s): Ichiba M, Nakamura M, Sano A
  • Publisher: 医学書院
• [Book] 双極性障害. 総合臨床「処方計画法」 (2008)
  • Author(s): 中村雅之, 佐野輝
  • Publisher: 永井書店
• [Book] chorea acanthocytosis ; 内科学 第九版 (2007)
  • Author(s): 佐野輝
  • Publisher: 朝倉書店
• [Book] Model of Chorea-Acanthocytosis, Neuroacanthocytosis Syndromes II (2007)
  • Author(s): Nakamura, M., Katoh, Y., Kurano, Y., Ichiba, M., Matsuda, M., Katoh, M., Ueno, S., & Sano. A.
  • Publisher: Springer, Berlin, Germany
• [Book] chorea acanthocytosis;内科学第九版 (2007)
  • Author(s): 佐野輝
  • Publisher: 朝倉書店